bluuebunny/crossref_metadata_2025 huggingface dataset:
An open label clinical trial to evaluate the utility of a hydrolysed fish and rice starch elimination diet for the diagnosis of adverse food reactions in dogs
Authors: Matricoti Irina , Noli Chiara
Published: August 2018

Background

The diagnosis of adverse food reaction (AFR) is based on an eight week elimination diet (ED) and is confirmed by relapse upon re‐challenge with the previously fed diet. Hydrolysed EDs are commonly used for this purpose.

Objective

To evaluate a commercially available hydrolysed fish protein and rice starch ED for the diagnosis of AFR.

Animals

Fifty nonseasonally pruritic dogs.

Methods and materials

Pruritus was assessed with a Visual Analog Scale, lesions with the Canine Atopic Dermatitis Lesions Index and quality of life with a validated questionnaire on days 0 and 56. Antimicrobial treatments were permitted during the first four weeks, and corticosteroids and oclacitinib during the first six weeks. Dogs showing at least 50% pruritus improvement were separately challenged with their prior diet, fish and rice.

Results

Thirty eight dogs completed the ED, four were dropped out due to worsening clinical signs, three to low palatability and five were lost to follow‐up. In 24 dogs, pruritus improved by >50% and 22 underwent dietary challenges. Of these, 15 reacted to their prior diets and were diagnosed with AFR, whereas seven did not relapse (and a diagnosis of AFR was considered to be doubtful). Five dogs reacted to fish and four to rice. Of the 14 dogs in which pruritus did not improve, some underwent a second ED and others were successfully treated for atopic dermatitis.

Conclusion and clinical importance

The hydrolysed fish and rice diet seemed to be a useful ED for the diagnosis of AFR, even in dogs allergic to fish or rice.
Non‐target‐site mechanism of glyphosate resistance in Italian ryegrass (Lolium multiflorum)
Authors: Kurata Kohei , Niinomi Yuki , Shimono Yoshiko , Miyashita Masahiro , Tominaga Tohru
Published: August 2018

In Shizuoka Prefecture, Japan, glyphosate‐resistant Lolium multiflorum is a serious problem on the levees of rice paddies and in wheat fields. The mechanism of resistance of this biotype was analyzed. Based on LD50, the resistant population was 2.8–5.0 times more resistant to glyphosate than the susceptible population. The 5‐enolpyruvyl‐shikimate‐3‐phosphate synthase (EPSPS) gene sequence of the resistant biotype did not show a non‐synonymous substitution at Pro106, and amplification of the gene was not observed in the resistant biotype. The metabolism and translocation of glyphosate were examined 4 days after application through the direct detection of glyphosate and its metabolite aminomethylphosphonic acid (AMPA) using liquid chromatograph‐tandem mass spectrometer (LC‐MS/MS). AMPA was not detected in either biotype in glyphosate‐treated leaves or the other plant parts. The respective absorption rates of the susceptible and resistant biotypes were 37.90 ± 3.63% and 41.09 ± 3.36%, respectively, which were not significantly different. The resistant biotype retained more glyphosate in a glyphosate‐treated leaf (91.36 ± 1.56% of absorbed glyphosate) and less in the untreated parts of shoots (5.90 ± 1.17%) and roots (2.76 ± 0.44%) compared with the susceptible biotype, 79.58 ± 3.73%, 15.77 ± 3.06% and 4.65 ± 0.89%, respectively. The results indicate that the resistance mechanism is neither the acquisition of a metabolic system nor limiting the absorption of glyphosate but limited translocation of the herbicide in the resistant biotype of L. multiflorum in Shizuoka Prefecture.
Flow-Induced Steam Valve Vibrations—A Literature Review of Excitation Mechanisms, Preventive Measures, and Design Improvements
Authors: Domnick Clemens Bernhard , Brillert Dieter
Published: August 2018

Steam turbine inlet valves are used to control the power output of steam turbines for power generation. These valves may be subject to vibration under certain operating conditions, especially in part-load operation. Several research papers and reports show that elevated valve vibrations can result in damage to parts of a steam turbine installation. A comprehensive literature review considering 43 different valves investigated in 51 studies reveals the effects causing vibrations. The physics of these effects are explained and methods for reducing flow-induced dynamic forces are presented based on the findings published in the literature. A classification scheme for typical valve designs is developed and the design features are evaluated in terms of valve vibration. Numerical methods for analyzing the fluid dynamics of valves are also presented.
Numerical Investigation of Transition of Flow Condensation in Microchannel
Authors: Park Il Seouk , Son Jong Hyeon
Published: August 2018

Due to the miniaturization of electronic devices and advanced machines, the micro-channel phase change heat transfer is used for heat removal on limited surfaces. However, since the complexity of the phase change phenomenon, it is difficult to numerically analyze the phase change phenomenon inside the microchannel. In this study, the flow condensation problem of FC-72 fluid in a microchannel is numerically analyzed with the phase change model. SST k-omega turbulence model is used and Volume of Fluid method is used for tracking the gas-liquid interface inside micro-channels. The condensation phenomenon is analyzed by applying the phase change model based on the difference of the phase interface and saturated temperature. The transition of two-phase flow pattern, cross-sectional velocity profiles in a micro-channel are studied according to the inlet mass flux and the heat flux at the channel wall surface. The heat transfer coefficient was compared with the experimental results and it is confirmed that the heat transfer coefficient at the wall increase when the inlet mass flux increase. Also, the channel wall side surface temperature profiles, changes of isotherms, and velocity vector field inside channel due to liquid-phase creation are presented.
Water-Silicone Oil Two-Phase Flow Hydrodynamics in a Square Glass Microchannel
Authors: Wu Zan , Svensson Astrid , Qian Jin-yuan , Sunden Bengt
Published: August 2018

This work visualized water-silicone oil two-phase flow patterns both at the inlet cross-junction and in the main square microchannel with a channel width of 400 μm. Tubing/threading, dripping and jetting were identified at the inlet junction while annular, slug and droplet flows were categorized in the main microchannel at 50 mm downstream of the junction. Flow patterns were represented in terms of superficial velocities and dimensionless numbers. Compared to water-silicone oil flow, addition of surfactant sodium dodecyl sulfate (SDS) in water, with a dilute SDS concentration of 1000 ppm, narrows the dripping regime and widens the jetting regime at the inlet junction, while narrows the slug flow regime and widens the droplet flow regime in the main microchannel. A decrease in dynamic interfacial tension due to SDS addition is supposed to be the reason for such a flow pattern modification. Besides, for slug flow, the slug length can be scaled as a power law of the flow rate ratio and the Capillary number of the organic phase. The slug velocity is linearly dependent on the bulk average velocity for both cases with and without SDS addition.
Effect of By-Pass on the Heat Transfer Coefficient During Density Wave Oscillations in a Horizontal Mini-Channel
Authors: Fernandino Maria , Dorao Carlos A.
Published: August 2018

Two phase flow instabilities and in particular density wave oscillations, DWO, are strongly dependent on the internal and external characteristics of the system. Although significant work has been done investigating the characteristics of the stability of the oscillations, the effect of the oscillations on the heat transfer coefficient demands further research. In this work, the influence of a parallel bypass to the test section on the heat transfer coefficient during density wave oscillations is studied. It is observed that in the case of small amplitude DWO the influence of the bypass is negligible, while for the case of large amplitude DWO that reach conditions of flow reversal the heat transfer coefficient can be enhanced. This fact is attributed to cold liquid entering at the outlet of the test section from the bypass preventing the dryout of the wall at high qualities.
Suppressing droplet coalescence and aggregation in immiscible homopolymer blends by interfacially cross-linked compatibilizers
Authors: Nasrollah Gavgani Jaber , Goharpey Fatemeh , Velankar Sachin , Foudazi Reza
Published: August 2018

In this work, we study the effect of reactive compatibilization on morphological and rheological properties of immiscible homopolymer blends of polydimethylsiloxane (PDMS) and polyisoprene (PI). The blend systems contained a chemical reaction between amine-functionalized PDMS and maleic anhydride-functionalized PI additives at high temperatures. Interfacially cross-linked compatibilizers obtained with this procedure are investigated through dynamic rheological measurements and Fourier transform infrared spectroscopy. The results show that the interfacial cross-linking constituting strong heterogeneous network is symmetric, as it reduces the sizes of the dispersed phase with higher stability in both compatibilized PI-continuous and PDMS-continuous blends compared to their uncompatibilized counterparts. A complete suppression of droplet coalescence can be concluded due to the superposition of linear viscoelasticity of the reactively compatibilized blends after different shearing protocols. In the previous work [C. DeLeo et al., J. Rheol. 55(4), 713–731 (2011)], however, the weak network at room temperature was found to have an asymmetric effect on the suppression of drop coalescence.
Multiple stimuli-responsive rheological behavior of a functionalized telechelic associative model polymer in aqueous solution
Authors: Du Zhukang , Dong Renfeng , Ke Kang , Ren Biye
Published: August 2018

Hydrophobically modified telechelic associative polymers (TAPs) composed of hydrophilic backbone and two hydrophobic end groups can form dynamic transient networks in water and have been widely used as thickeners for improving solution rheological properties in many industrial fields. In this work, we designed and prepared a novel telechelic associative model polymer (FcC11AzoTAP) end-functionalized by photo-responsive azobenzene (Azo) unit along with the redox-responsive ferrocene extremity, which was used to investigate the effects of stimuli responsive behaviors such as redox reaction or/and photo isomerization of end groups on its solution aggregation and rheological properties. It has been demonstrated that the network structures and rheological properties of FcC11AzoTAP aqueous solutions can be readily tuned by the magnitude of stimuli-responsive hydrophobicity change of end groups to a certain degree. Moreover, a rearrangement of network through bridge to inactive loop and/or pending arm transitions is proposed to describe the dense to sparse network conversion. This work will not only provide new insights into the effects of end groups on the network structure and rheological properties of solution but it also opens a new perspective for some special applications of TAPs in industrial fields.
Effect of Using a Sit-Stand Desk on Ratings of Discomfort, Fatigue, and Sleepiness Across a Simulated Workday in Overweight and Obese Adults
Authors: Kowalsky Robert J. , Perdomo Sophy J. , Taormina John M. , Kline Christopher E. , Hergenroeder Andrea L. , Balzer Jeffrey R. , Jakicic John M. , Gibbs Bethany Barone
Published: August 2018

Background: Limited research examines the influence of sit-stand desks on ratings of discomfort, sleepiness, and fatigue. This study evaluated the time course of these outcomes over 1 day. Methods: Adults (N = 25) completed a randomized cross-over study in a laboratory with two 8-hour workday conditions: (1) prolonged sitting (SIT) and (2) alternating sitting and standing every 30 minutes (SIT-STAND). Sleepiness was assessed hourly. Discomfort, physical fatigue, and mental fatigue were measured every other hour. Linear mixed models evaluated whether these measures differed across conditions and the workday. Effect sizes were calculated using Cohen’s d. Results: Participants were primarily white (84%) males (64%), with mean (SD) body mass index of 31.9 (5.0) kg/m2 and age 42 (12) years. SIT-STAND resulted in decreased odds of discomfort (OR = 0.37, P = .01) and lower overall discomfort (β = −0.19, P < .001, d = 0.42) versus SIT. Discomfort during SIT-STAND was lower in the lower and upper back, but higher in the legs (all Ps< .01, d = 0.26–0.42). Sleepiness (β = −0.09, P = .01, d = 0.15) and physical fatigue (β = −0.34, P = .002, d = 0.34) were significantly lower in SIT-STAND. Mental fatigue was similar across conditions. Conclusions: Sit-stand desks may reduce acute levels of sleepiness, physical fatigue, and both overall and back discomfort. However, levels of lower extremity discomfort may be increased with acute exposure.
Springtail-inspired superomniphobic surface with extreme pressure resistance
Authors: Yun Geun-Tae , Jung Woo-Bin , Oh Myung Seok , Jang Gyu Min , Baek Jieung , Kim Nam Il , Im Sung Gap , Jung Hee-Tae
Published: August 2018

First springtail-inspired omniphobic surface by hierarchical structure to repel liquids even with high pressure of droplets.
Vector Competence of Geographical Populations of Ornithodoros turicata for the Tick-Borne Relapsing Fever Spirochete Borrelia turicatae
Authors: Krishnavajhala Aparna , Armstrong Brittany A. , Lopez Job E.
Published: August 2018

Several knowledge gaps exist in the vector competence of various geographical populations ofO. turicatathat transmitB. turicatae. A western population of this tick is distributed from California to Texas, and an eastern population exists in Florida. Utilizing western and eastern populations of the vector, we studied acquisition and transmission of twoB. turicataeisolates. Regardless of the isolate used, infection frequencies were poor in mice after the eastern population feeding on them. Since salivary gland colonization is essential forB. turicataetransmission, these tissues were further evaluated. Interestingly, the salivary glands from the two populations were similarly colonized withB. turicatae.These findings suggest the role of tick saliva in the establishment of infection and that the salivary glands may be a bottleneck for successful transmission.
Association betweenHelicobacter pyloriinfection and tumor markers: an observational retrospective study
Authors: Xu Mei-Yan , Cao Bing , Chen Yan , Musial Natalie , Wang Shuai , Yin Jian , Liu Lan , Lu Qing-Bin
Published: August 2018

Objective

Helicobacter pyloriinfection is a major cause of several cancers such as gastric, pancreatic and lung. The relationship betweenH. pyloriand tumour markers continues to remain unclear. The primary goal of this study is to clarify the associations betweenH. pyloriinfection and six tumour markers (ie, carcinoembryonic antigen (CEA), cancer antigen (CA) 153, CA199, CA724, CA125 and alpha-fetoprotein (AFP)). The secondary goal is to provide understanding for further research aboutH. pyloriinfection and gastrointestinal cancer.

Design

Observational retrospective study.

Setting

The study was performed in Beijing, China, where enrolled subjects had all passed health examinations during the period of 2012–2016. Subjects were categorised intoH. pylori(+) andH. pylori(–) group according to their infection status and the measured six biomarkers. We used logistic regression models and generalised linear models to explore the associations betweenH. pyloriinfection and six tumour markers (ie, CEA, CA153, CA199, CA724, CA125 and AFP).

Participants

A total of 14 689 subjects were included and 6493 (44.2%) subjects were infected byH. pylori. The subjects had a mean age (1SD) of 45 (18) years. There were 4530 (31.0%) female subjects.

Results

After adjusting for the confounding factors, infections withH. pyloriwere found to be significantly associated with abnormal ratios in CEA, AFP and CA724 ofH. pylori(+) toH. pylori(–) groups. Significant positive correlation was found betweenH. pyloriinfection and CEA values (adjusted β=0.056; 95% CI 0.005 to 0.107; p=0.033).

Conclusions

In this observational retrospective study, we observed theH. pyloriinfections in a Chinese population and found higher CEA level inH. pylori-infected subjects and abnormal ratios in CEA, AFP and CA724 in infected subjects to uninfected subjects. These findings may provide a basis for future exploration withH. pyloriand tumour markers.
Case of mycobacteriosis in a pet ferret in Poland
Authors: Lipiec Marek , Radulski Lukasz , Iwaniak Wojciech
Published: August 2018

A seven-year-old dead pet ferret (Mustela putorius furo) was brought to the National Veterinary Research Institute, Department of Microbiology, to have the disease diagnosed and cause of death determined. Significant loss of fur and various numerous skin lesions—such as nodules, bruises and small scabs— were found. A prominent subcutaneous cyst filled with semiliquid mass was observed on the right hindlimb, and the left eyelid was slightly swollen left eyelid with symptoms of conjunctivitis. On the basis of combined findings, the authors concluded that the ferret’s death was caused by a generalized Mycobacterium aviumsubspecies avium infection. Some immunodeficiency resulting from ferret’s age could be a predisposing factor. A feral cat, which was the only animal the ferret had contacted several weeks before the appearance of the first clinical symptoms, was a possible source of infection.
An optimal data aggregation technique for physics-based applications
Authors: Joshi Upasna , Sharma Rajiv
Published: August 2018

In wireless sensor network (WSN), most of the devices function on batteries. These nodes or devices have inadequate amount of initial energy which are consumed at diverse rates, based on the power level and intended receiver. In sleep scheduling algorithms, most of the sensor nodes are turned to sleep state to preserve energy and improve the network lifetime (NL). In this paper, an energy-efficient dynamic cluster-based protocol is proposed for WSN especially for physics-based applications. Initially, the network is divided into small clusters using adaptive clustering. The clusters are managed by the cluster heads. The cluster heads are elected based on the novel dynamic threshold. Afterwards, general variable neighborhood search is used to obtain the energy-efficient paths for inter-cluster data aggregation which is used to communicate with the sink. The performance of the proposed method is compared with competitive energy-efficient routing protocols in terms of various factors such as stable period, NL, packets sent to base station and packets sent to cluster head. Extensive experiments prove that the proposed protocol provides higher NL than the existing protocols.
Diversity of interaction solutions to the (3+1)-dimensional Kadomtsev–Petviashvili–Boussinesq-like equation
Authors: Lü Jianqing , Bilige Sudao
Published: August 2018

The (3[Formula: see text]+[Formula: see text]1)-dimensional Kadomtsev–Petviashvili–Boussinesq-like equation has some advantages when it is applied to solve engineering problems. Via using the Hirota method and symbolic computation Mathematica, we get the lump, interaction solution and breather-wave solution under certain constraints. An interesting feature of the resulting interaction solution involves arbitrary function. Illustrative examples of the resulting solution are shown by drawing.
Noether symmetry classifications of generalized diagonal spaces
Authors: Jamal Sameerah , Shabbir Ghulam , Mathebula A. S.
Published: August 2018

The general form of Noether symmetries admitted by Lagrangians corresponding to a diagonal metric are determined. We apply this general result in order to classify different metric functions for the determination of Noether generators for the equations of motion. For the two broad cases considered, we identify symmetry algebras up to dimension thirteen.
Sino-Algerian Strategic Cooperation:Towards a New Stage of Development
Authors: Matallah Siham
Published: August 2018

Algeria strongly welcomed cooperation with China along with its search for an economic and political partner that respects Algeria’s sovereignty, ethnicity, religious, and cultural peculiarities, especially as Algeria suffered a bitter experience under the French colonial rule that deprived it of a window into global markets even after the achievement of independence, and China’s partnership seemed like an auspicious beginning for the Algerian economy. Indeed, China opened its arms to Algeria and became its largest trading partner, surpassing France that has traditionally been Algeria’s number one supplier. Both countries are committed to carrying forward their friendship in a spirit of equality and mutual respect, mutual trust, mutual benefit, and common gain. On the one hand, China attaches great importance to its bilateral relations with Algeria, which were raised to a comprehensive strategic partnership level in February 2014, and on the other hand, the Algerian government played a very important role in encouraging Chinese companies to invest in various fields, adding new depth to the Sino-Algerian relationship.
Workflow model for the digitization of mudrocks
Authors: Buckman Jim , Mahoney Carol , Bankole Shereef , Couples Gary , Lewis Helen , Wagner Thomas , März Christian , Blanco Vladimir , Stow Dorrik
Published: August 2018

Mudrocks are highly heterogeneous in a range of physical and chemical properties, including: porosity and permeability, fissility, colour, particle composition, size, orientation, carbon loading, degree of compaction, and diagenetic overprint. It is therefore important that the maximum information be extracted as efficiently and completely as possible. This can be accomplished through high-resolution analysis of polished thin sections by scanning electron microscopy (SEM), with the collection of large-area images and X-ray elemental map montages, and the application of targeted particle analysis. A workflow model, based on these techniques, for the digitization of mudrocks is presented herein. A range of the data that can be collected and the variety of analyses that can be achieved are also illustrated. Data collection is discussed in terms of inherent problems with acquisition, storage, transfer and manipulation, which can be time-consuming and non-trivial. Similar information and resolutions can be achieved through other techniques, such as QEMSCAN and infra-red (IR)/Raman spectroscopic mapping. These can be seen as complementary to the workflow described herein.
On-the-fly Vertex Reuse for Massively-Parallel Software Geometry Processing
Authors: Kenzel Michael , Kerbl Bernhard , Tatzgern Wolfgang , Ivanchenko Elena , Schmalstieg Dieter , Steinberger Markus
Published: August 2018

Due to its flexibility, compute mode is becoming more and more attractive as a way to implement many of the algorithms part of a state-of-the-art rendering pipeline. A key problem commonly encountered in graphics applications is streaming vertex and geometry processing. In a typical triangle mesh, the same vertex is on average referenced six times. To avoid redundant computation during rendering, a post-transform cache is traditionally employed to reuse vertex processing results. However, such a vertex cache can generally not be implemented efficiently in software and does not scale well as parallelism increases. We explore alternative strategies for reusing per-vertex results on-the-fly during massively-parallel software geometry processing. Given an input stream divided into batches, we analyze the effectiveness of sorting, hashing, and intra-thread-group communication for identifying and exploiting local reuse potential. We design and present four vertex reuse strategies tailored to modern GPU architectures. We demonstrate that, in a variety of applications, these strategies not only achieve effective reuse of vertex processing results, but can boost performance by up to 2-3x compared to a naïve approach. Curiously, our experiments also show that our batch-based approaches exhibit behavior similar to the OpenGL implementation on current graphics hardware.
Importance Sampling of Many Lights with Adaptive Tree Splitting
Authors: Conty Estevez Alejandro , Kulla Christopher
Published: August 2018

We present a technique to importance sample large collections of lights (including mesh lights as collections of small emitters) in the context of Monte-Carlo path tracing. A bounding volume hierarchy over all emitters is traversed at each shading point using a single random number in a way that importance samples their predicted contribution. The tree aggregates energy, spatial and orientation information from the emitters to enable accurate prediction of the effect of a cluster of lights on any given shading point. We further improve the performance of the algorithm by forcing splitting until the importance of a cluster is sufficiently representative of its contents.
Phantom Ray-Hair Intersector
Authors: Reshetov Alexander , Luebke David
Published: August 2018

We present a new approach to ray tracing swept volumes along trajectories defined by cubic Bézier curves. It performs at two-thirds of the speed of ray-triangle intersection, allowing essentially even treatment of such primitives in ray tracing applications that require hair, fur, or yarn rendering.

At each iteration, we approximate a radially symmetric swept volume with a tangential cone. A distance from the ray-cone intersection to the cone's base is then used to compute the next curve parameter t. When this distance is zero, the ray intersects the swept volume and the cone at the same point and we stop the iterations. To enforce continuity of the iterative root finding, we introduce "phantom" intersection, padding the cone until it touches the ray if the ray-cone intersection does not exist.
Role of extracellular matrix in the pathogenesis of pulmonary arterial hypertension
Authors: Thenappan Thenappan , Chan Stephen Y. , Weir E. Kenneth
Published: August 2018

Pulmonary arterial hypertension (PAH) is characterized by remodeling of the extracellular matrix (ECM) of the pulmonary arteries with increased collagen deposition, cross-linkage of collagen, and breakdown of elastic laminae. Extracellular matrix remodeling occurs due to an imbalance in the proteolytic enzymes, such as matrix metalloproteinases, elastases, and lysyl oxidases, and tissue inhibitor of matrix metalloproteinases, which, in turn, results from endothelial cell dysfunction, endothelial-to-mesenchymal transition, and inflammation. ECM remodeling and pulmonary vascular stiffness occur early in the disease process, before the onset of the increase in the intimal and medial thickness and pulmonary artery pressure, suggesting that the ECM is a cause rather than a consequence of distal pulmonary vascular remodeling. ECM remodeling and increased pulmonary arterial stiffness promote proliferation of pulmonary vascular cells (endothelial cells, smooth muscle cells, and adventitial fibroblasts) through mechanoactivation of various signaling pathways, including transcriptional cofactors YAP/TAZ, transforming growth factor-β, transient receptor potential channels, Toll-like receptor, and NF-κB. Inhibition of ECM remodeling and mechanotransduction prevents and reverses experimental pulmonary hypertension. These data support a central role for ECM remodeling in the pathogenesis of the PAH, making it an attractive novel therapeutic target.
Increased thin filament activation enhances alternans in human chronic atrial fibrillation
Authors: Zile Melanie A. , Trayanova Natalia A.
Published: August 2018

Action potential duration (APD) alternans (APD-ALT), defined as beat-to-beat oscillations in APD, has been proposed as an important clinical marker for chronic atrial fibrillation (cAF) risk when it occurs at pacing rates of 120–200 beats/min. Although the ionic mechanisms for occurrence of APD-ALT in human cAF at these clinically relevant rates have been investigated, little is known about the effects of myofilament protein kinetics on APD-ALT. Therefore, we used computer simulations of single cell function to explore whether remodeling in myofilament protein kinetics in human cAF alters the occurrence of APD-ALT and to uncover how these mechanisms are affected by sarcomere length and the degree of cAF-induced myofilament remodeling. Mechanistically based, bidirectionally coupled electromechanical models of human right and left atrial myocytes were constructed, incorporating both ionic and myofilament remodeling associated with cAF. By comparing results from our electromechanical model with those from the uncoupled ionic model, we found that intracellular Ca2+ concentration buffering of troponin C has a dampening effect on the magnitude of APD-ALT (APD-ANM) at slower rates (150 beats/min) due to the cooperativity between strongly bound cross-bridges and Ca2+-troponin C binding affinity. We also discovered that cAF-induced enhanced thin filament activation enhanced APD-ANM at these clinically relevant heart rates (150 beats/min). In addition, longer sarcomere lengths increased APD-ANM, suggesting that atrial stretch is an important modulator of APD-ALT. Together, these findings demonstrate that myofilament kinetics mechanisms play an important role in altering APD-ALT in human cAF.

NEW & NOTEWORTHY Using a single cell simulation approach, we explored how myofilament protein kinetics alter the formation of alternans in action potential duration (APD) in human myocytes with chronic atrial fibrillation remodeling. We discovered that enhanced thin filament activation and longer sarcomere lengths increased the magnitude of APD alternans at clinically important pacing rates of 120–200 beats/min. Furthermore, we found that altered intracellular Ca2+ concentration buffering of troponin C has a dampening effect on the magnitude of APD alternans.
Relationships of Insulin Action to Age, Gender, Body Mass Index, and Waist Circumference Present Diversely in Different Glycemic Statuses among Chinese Population
Authors: Pang Shao-jie , Man Qing-Qing , Song Shuang , Song Peng-Kun , Liu Zhen , Li Yu-Qian , Jia Shan-Shan , Wang Jing-Zhong , Zhao Wen-Hua , Zhang Jian
Published: August 2018

Introduction. To study the influence of different glycemic statuses on the relationship of insulin action to age, gender, body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) among Chinese population. Methods. A total of 35,327 participants (17,456 males and 17,871 females) were included in this nationally representative cross-sectional study. Glycemic status was defined according to the 2010 American Diabetes Association criteria. Fasting insulin was measured by the chemiluminescence method. Results. Insulin and HOMA-IR levels were the highest in newly diagnosed diabetes and were lowest in normal fasting glucose (NFG) (P<0.001). Insulin and HOMA-IR levels were higher in females (P<0.001) than in males with previously diagnosed diabetes and impaired fasting glucose (IFG) and NFG, meanwhile decreased with age (P<0.001) among IFG and NFG participants. As compared with participants with a BMI from 18.5 to 19.9, those in the lowest BMI category (<18.5) had a significantly elevated risk of IR (OR, 1.96; 95% CI, 1.01–3.80), as did those in the higher BMI categories among NFG participants. The risk of IR increased with WC and WHtR, and the response was linear (P<0.001 for linear trend) for the participants with NFG but not in those with IFG. Conclusions. Different glycemic statuses significantly affect the relationships of insulin action to age, gender, BMI, WC, and WHtR among Chinese population.
Significance of Glioma Stem-Like Cells in the Tumor Periphery That Express High Levels of CD44 in Tumor Invasion, Early Progression, and Poor Prognosis in Glioblastoma
Authors: Nishikawa Masahiro , Inoue Akihiro , Ohnishi Takanori , Kohno Shohei , Ohue Shiro , Matsumoto Shirabe , Suehiro Satoshi , Yamashita Daisuke , Ozaki Saya , Watanabe Hideaki , Yano Hajime , Takahashi Hisaaki , Kitazawa Riko , Tanaka Junya , Kunieda Takeharu
Published: August 2018

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and a subpopulation of glioma stem-like cells (GSCs) is likely responsible for the invariable recurrence following maximum resection and chemoradiotherapy. As most GSCs that are located in the perivascular and perinecrotic niches should be removed during tumor resection, it is very important to know where surviving GSCs are localized. Here, we investigated the existence and functions of GSCs in the tumor periphery, which is considered to constitute the invasion niche for GSCs in GBM, by analyzing expression of stem cell markers and stem cell-related molecules and measuring particular activities of cultured GSCs. In addition, the relationship between GSCs expressing particular stem cell markers and pathological features on MRI and prognosis in GBM patients was analyzed. We showed that GSCs that express high levels of CD44 are present in the tumor periphery. We also found that vascular endothelial growth factor (VEGF) is characteristically expressed at a high level in the tumor periphery. Cultured GSCs obtained from the tumor periphery were highly invasive and have enhanced migration phenotype, both of which were markedly inhibited by CD44 knockdown. Higher expression of CD44 in the tumor periphery than in the core was correlated with a highly invasive feature on MRI and was associated with early tumor progression and worse survival, whereas lower expression of CD44 in the tumor periphery corresponded to low invasion and was associated with longer survival. The low invasion type on MRI tended to show high levels of VEGF expression in the tumor periphery, thus presenting the tumor with high proliferative activity. These results imply the significance of GSCs with high levels of CD44 expression in the tumor periphery compared to the core, not only in tumor invasion but also rapid tumor progression and short survival in patients with GBM.
Ultrasound Grade of Liver Steatosis Is Independently Associated with the Risk of Metabolic Syndrome
Authors: Mustapic Sanda , Ziga Sead , Matic Vladimir , Bokun Tomislav , Radic Bozo , Lucijanic Marko , Marusic Srecko , Babic Zarko , Grgurevic Ivica
Published: August 2018

The aim of the study was to explore (a) prevalence and grade of nonalcoholic fatty liver (NAFL) among outpatients referred for abdominal ultrasound (US) examination and (b) relationship between the presence and severity of liver steatosis and metabolic syndrome (MS). This was a retrospective analysis of patients without history of liver disease examined by abdominal US in the University hospital setting. US was used to detect and semiquantitatively grade (0-3) liver steatosis. Data on patients’ age, gender, body mass index (BMI), impaired glucose metabolism (IGM), atherogenic dyslipidaemia (AD), raised blood pressure (RBP), transaminases, and platelet counts were obtained from medical records. MS was defined as having at least 3 of the following components: obesity, IGM, AD, and RBP. Of the 631 patients (median age 60 years, median BMI 27.4 kg/m2, and 57.4% females) 71.5% were overweight and 48.5% had NAFL. In the subgroup of 159 patients with available data on the components of MS, patients with higher US grade of steatosis had significantly higher BMI and increased prevalence of obesity, IGM, AD, RBP, and accordingly more frequently had MS, whereas they did not differ in terms of age and gender. NAFL was independently associated with the risk of having MS in a multivariate model adjusted for age, gender, BMI, and IGM. The grade of liver steatosis did not correlate with the presence of liver fibrosis. We demonstrated worrisome prevalence of obesity and NAFL in the outpatient population from our geographic region. NAFL is independently associated with the risk of having MS implying worse prognosis.
Cripto-1 Plasmid DNA Vaccination Targets Metastasis and Cancer Stem Cells in Murine Mammary Carcinoma
Authors: Witt Kristina , Ligtenberg Maarten A. , Conti Laura , Lanzardo Stefania , Ruiu Roberto , Wallmann Tatjana , Tufvesson-Stiller Helena , Chambers Benedict J. , Rolny Charlotte , Lladser Alvaro , Lundqvist Andreas , Cavallo Federica , Kiessling Rolf
Published: August 2018

Metastatic breast cancer is a fatal disease that responds poorly to treatment. Cancer vaccines targeting antigens expressed by metastatic breast cancer cells and cancer stem cells could function as anticancer therapies. Cripto-1 is an oncofetal protein overexpressed in invasive breast cancer and cancer-initiating cells. In this study, we explored the potential of a Cripto-1–encoding DNA vaccine to target breast cancer in preclinical mouse models. BALB/c mice and BALB-neuT mice were treated with a DNA vaccine encoding mouse Cripto-1 (mCr-1). BALB/c mice were challenged with murine breast cancer 4T1 cells or TUBO spheres; BALB-neuT mice spontaneously developed breast cancer. Tumor growth was followed in all mouse models and lung metastases were evaluated. In vitro assays were performed to identify the immune response elicited by vaccination. Vaccination against mCr-1 reduced primary tumor growth in the 4T1 metastatic breast cancer model and reduced lung metastatic burden. In BALB-neuT mice, because the primary tumors are Cripto-1 negative, vaccination against mCr-1 did not affect primary tumors but did reduce lung metastatic burden. Spheroid-cultured TUBO cells, derived from a BALB/neuT primary tumor, develop a cancer stem cell–like phenotype and express mCr-1. We observed reduced tumor growth in vaccinated mice after challenge with TUBO spheres. Our data indicate that vaccination against Cripto-1 results in a protective immune response against mCr-1 expressing and metastasizing cells. Targeting Cripto-1 by vaccination holds promise as an immunotherapy for treatment of metastatic breast cancer. Cancer Immunol Res; 6(11); 1417–25. ©2018 AACR.
PPAR-Induced Fatty Acid Oxidation in T Cells Increases the Number of Tumor-Reactive CD8+ T Cells and Facilitates Anti–PD-1 Therapy
Authors: Chowdhury Partha S. , Chamoto Kenji , Kumar Alok , Honjo Tasuku
Published: August 2018

Although PD-1 blockade cancer immunotherapy has shown potential for a wide range of patients with cancer, its efficacy is limited, in part, due to the loss of effector cytotoxic T lymphocytes (CTLs) via terminal differentiation–induced apoptosis. We previously demonstrated that mitochondrial activation, by the agonists of peroxisome proliferator–activated receptor γ (PPARγ) coactivator 1-α (PGC-1α)/transcription factor complexes, had synergistic effects with a PD-1–blocking monoclonal antibody in a mouse tumor model. In the current study, we examined the molecular mechanism of the synergistic effects of bezafibrate, an agonist of PGC-1α/ PPAR complexes, which enhanced the tumoricidal effects of PD-1 blockade. Bezafibrate activated CTL mitochondria and upregulated oxidative phosphorylation as well as glycolysis, resulting in more proliferation of naïve T cells and improved effector function in CTLs. Bezafibrate also increased fatty acid oxidation (FAO) and mitochondrial respiratory capacity, which supports the extra energy demands of cells in emergencies, allowing cell survival. Carnitine palmitoyl transferase 1 (Cpt1), which is needed for FAO, and Bcl2 were both upregulated. Cpt1 and Bcl2 can form a complex to prevent apoptosis of CTLs. Together, these results indicate that bezafibrate increases or maintains the number of functional CTLs by activating mitochondrial and cellular metabolism, leading in turn to enhanced antitumor immunity during PD-1 blockade. Cancer Immunol Res; 6(11); 1375–87. ©2018 AACR.
MicroRNA Dysregulation Associated with Red Blood Cell Storage
Authors: Chen Xiaojie , Xie Xuhong , Xing Yanfen , Yang Xiuhua , Yuan Zhaohu , Wei Yaming
Published: August 2018

Introduction: Stored red blood cells (RBCs) undergo storage lesions involving morphological, physiological and biochemical changes. MicroRNAs (miRNAs) have important functions in cell apoptosis and life processes. Therefore, the aim of this study was to explore potential roles of miRNAs in the damage of stored RBCs. Methods: Blood samples were collected from 13 healthy male O-type donors, and leuko-reduced RBCs were divided into fresh RBC group and 20-day storage RBC group. Results: Eight predicted miRNAs with modified expressions with an intersection ≥ 3 were found dysregulated in the 20-day storage RBC group and involved in apoptosis and senescence signaling pathway: miR-31-5p, miR-196a-5p, miR-203a, miR-654-3p and miR-769-3p were increased, while miR-96-5P, miR-150-5P and miR-197-3p were decreased. Evidence associating miR-31-5p, miR-203a, miR-654 and miR-769 to RBCs or blood in general are not available. Conclusions: Dysregulated miRNAs might represent potential biomarkers to identify storage lesions, and their detection might help to evaluate the quality of stored RBCs.
A Randomized Controlled Trial on Efficacy and Safety of Trocar-Site Infiltration with Lidocaine for Postoperative Pain Relief after Diagnostic Laparoscopy
Authors: Joe-Ikechebelu Ngozi N. , Eleje George Uchenna , Ugwu Emmanuel Onyebuchi , Okafor Chidimma Donatus , Nwachukwu Cyril Emeka , Okam Princeston C. , Ogboji Obinna E. , Ikechebelu Joseph Ifeanyichukwu
Published: August 2018

Background/Aims: To compare the efficacy and safety of trocar-site infiltration with lidocaine and no intervention for postoperative pain relief after diagnostic laparoscopy. Methods: A randomized clinical trial of women with infertility scheduled for diagnostic laparoscopy without additional procedures in Life Institute for Endoscopy at Life Specialist Hospital, Nnewi, Nigeria. One hundred and ninety nine women were assigned at random to either trocar-site infiltration with lidocaine (n = 100) or no intervention (n = 99). Pain was assessed using visual analogue scale (VAS) scores at 2 and 4 h post surgery. The primary endpoints were postoperative pain control and time to first request of analgesia, while the secondary endpoints were total analgesic consumption, shoulder pain, and side effects. Evaluations between the groups were done according to the principle of intention-to-treat. Results: Baseline characteristics were similar. A nonsignificant reduction was observed in the VAS in the intervention group at base line, 2 and 4 hours into the postoperative period in comparison with no intervention (p > 0.05), and the time to first analgesic requirement was not significantly prolonged (p > 0.05). The mean total consumption of rescue analgesia was not significantly reduced (p > 0.05). Conclusions: Postoperative injection of lidocaine in laparoscopy port sites did not significantly improve pain scores after diagnostic laparoscopy. Clinical trial registration: PACTR201611001263105
Cranial Rhabdomyosarcoma Masquerading as Infectious Mastoiditis: Case Report and Literature Review
Authors: Do Thao N. , Linabery Amy M. , Patterson Richard J. , Tu  Albert 
Published: August 2018

Background: Rhabdomyosarcoma originating in the mastoid is rare and may be misdiagnosed as an infectious mastoiditis due to overlapping clinical and imaging features. We aimed to identify distinguishing characteristics to facilitate earlier diagnosis and treatment. Method: Here we describe a case report and a systematic review of 23 reports describing previous cases of mastoid rhabdomyosarcoma. We compare these patients to a systematic review of patients with infectious mastoiditis and identify distinguishing clinical features. Results: A total of 43 patients with rhabdomyosarcoma of the mastoid were identified and compared with patients with mastoiditis. Rhabdomyosarcoma patients were more likely to present with a mass (86%) or cranial nerve dysfunction (83.7%), while mastoiditis patients were more likely to have fever (72.4%), pain (48.2%), and present at a younger age (4.4 vs. 6.1 years). The average lifespan with rhabdomyosarcoma of the mastoid was 7.1 months after diagnosis, with 41.7% of patients alive at the time of report. Conclusions: Based on abstracted and aggregated information, we identified unique features observed more frequently in each of rhabdomyosarcoma and mastoiditis. These predictive features allow for the differentiation of each diagnosis and avoid the delay of proper treatment.
Expression Levels of Follicle-Stimulating Hormone Receptor and Implication in Diagnostic and Therapeutic Strategy of Ovarian Cancer
Authors: Wei Suocheng , Lai Luju , Yang Juan , Zhuandi Gong
Published: August 2018

Background: Follicle-stimulating hormone receptor (FSHR) has been shown to be expressed in ovarian cancer. Methods: Here we have summarized the potential therapeutic and diagnostic implication of FSHR in the ovarian cancers based on a review of the literature. Results: Current research indicates that FSHR comprises several variants: FSHR-1, FSHR-2, FSHR-3 and FSHR-4. Only FSHR-1 and FSHR-3 have biological roles. Although the level of FSHR differs in ovarian cancer tissues, few quantitative correlations have so far been reported on the expression levels of FSHR and carcinogenesis and progression of cancers. Conclusion: A comprehensive understanding of the role of FSHR in the ovarian cancers may help the search for novel therapeutic and diagnostic regimens and improve the management of cancer patients.
Recurrent Gastrointestinal Bleeding from Dieulafoy’s Lesions in a Patient with Type 1 von Willebrand Disease: A Rare Association
Authors: Cardoso Mariana Ferreira , Lourenço Luís Carvalho , Antunes Margarida , Carvalho e Branco Joana , Santos Liliana , Martins Alexandra , Reis Jorge A.
Published: August 2018

Von Willebrand disease (vWD) is the most prevalent hereditary bleeding disorder, affecting 0.6–1.3% of the population. While gastrointestinal bleeding from angiodysplasia is a well-known complication of vWD, the same is not true for Dieulafoy’s lesions (DLs). We report the case of a 21-year-old black male with type 1 vWD and 2 previous hospital admissions for severe anemia with no visible blood loss. In both episodes, DLs were identified and treated endoscopically, one in the stomach and another in the duodenum. The patient presented to the emergency department in September 2016 with dizziness, fatigue, and again no visible blood loss. He was hemodynamically stable, and laboratory workup showed a hemoglobin level of 3.4 g/dL. After transfusion of packed red blood cells, intravenous iron, and von Willebrand factor/factor VIII concentrate infusions, the patient underwent upper endoscopy and colonoscopy, which were normal. Small-bowel capsule endoscopy showed dark blood and a fresh clot in the proximal jejunum. At this site, push enteroscopy identified a pulsatile vessel with an overlying minimal mucosal defect, consistent with a DL, type 2b of the Yano-Yamamoto classification, which was successfully treated with adrenaline and 2 hemoclips. The patient remains stable after 18 months of follow-up, with a hemoglobin level of 13.2 g/dL. This is a case of recurrent severe occult gastrointestinal bleeding from multiple DL in a young patient with vWD who is otherwise healthy. Three other cases of DL bleeding in the setting of vWD have been reported in the literature, suggesting a possible association between these 2 entities.