bluuebunny/crossref_metadata_2025 huggingface dataset:
SR and LR Union Suture for the Treatment of Myopic Strabismus Fixus: Is Scleral Fixation Necessary?
Authors: Lam Carol P. S. , Yam Jason C. S. , Lau Flora H. S. , Fan Dorothy S. P. , Wong C. Y. , Yu Christopher B. O. , Lau Winnie W. Y.
Published: April 2015

Purpose. To evaluate and compare the effectiveness of scleral fixation SR and LR union suture and nonscleral fixation union suture for the treatment of myopic strabismus fixus.Methods. Retrospective review of 32 eyes of 22 patients with myopic strabismus fixus who had undergone union suture of superior rectus (SR) and lateral rectus (LR) with or without scleral fixation, and follow-up longer than 6 months at Hong Kong Eye Hospital from 2006 to 2013. Surgical techniques and outcomes in terms of ocular alignment are analyzed.Results. There is significant overall improvement both in postoperative angle of esodeviation (P<0.01) and postoperative range of movement (P=0.042). Comparing between the sclera fixation group (11 eyes) versus nonscleral fixation group (21 eyes), the postoperative horizontal deviation, the postoperative vertical deviation, successful outcome, and the change in horizontal deviation were not significantly different (P>0.05).Conclusions. Union suture of SR and LR is an effective procedure in correcting myopic strabismus fixus. Fixation of the union suture to the sclera does not improve surgical outcome.
A Note on Two-Agent Scheduling with Resource Dependent Release Times on a Single Machine
Authors: Liu Peng , Duan Lini
Published: April 2015

We consider a scheduling problem in which both resource dependent release times and two agents exist simultaneously. Two agents share a common single machine, and each agent wants to minimize a cost function dependent on its own jobs. The release time of eachA-agent’s job is related to the amount of resource consumed. The objective is to find a schedule for the problem of minimizingA-agent’s total amount of resource consumption with a constraint onB-agent’s makespan. The optimal properties and the optimal polynomial time algorithm are proposed to solve the scheduling problem.
Nanoparticle Enhanced MRI Scanning to Detect Cellular Inflammation in Experimental Chronic Renal Allograft Rejection
Authors: Alam S. R. , Tse G. H. , Stirrat C. , MacGillivray T. J. , Lennen R. J. , Jansen M. A. , Newby D. E. , Marson L. , Henriksen P. A.
Published: April 2015

Objectives. We investigated whether ultrasmall paramagnetic particles of iron oxide- (USPIO-) enhanced magnetic resonance imaging (MRI) can detect experimental chronic allograft damage in a murine renal allograft model. Materials and Methods. Two cohorts of mice underwent renal transplantation with either a syngeneic isograft or allograft kidney. MRI scanning was performed prior to and 48 hours after USPIO infusion using T2∗-weighted protocols. R2∗ values were calculated to indicate the degree of USPIO uptake. Native kidneys and skeletal muscle were imaged as reference tissues and renal explants analysed by histology and electron microscopy. Results. R2∗ values in the allograft group were higher compared to the isograft group when indexed to native kidney (median 1.24 (interquartile range: 1.12 to 1.36) versus 0.96 (0.92 to 1.04), P<0.01). R2∗ values were also higher in the allograft transplant when indexed to skeletal muscle (6.24 (5.63 to 13.51)) compared to native kidney (2.91 (1.11 to 6.46) P<0.05). Increased R2∗ signal in kidney allograft was associated with macrophage and iron staining on histology. USPIO were identified within tissue resident macrophages on electron microscopy. Conclusion. USPIO-enhanced MRI identifies macrophage.
Aesthetic Depigmentation of Gingival Smoker’s Melanosis Using Carbon Dioxide Lasers
Authors: Monteiro Luis Silva , Costa José Adriano , da Câmara Marco Infante , Albuquerque Rui , Martins Marco , Pacheco José Júlio , Salazar Filomena , Figueira Fernando
Published: April 2015

Melanic pigmentation results from melanin produced by the melanocytes present in the basal layer of the oral epithelium. One of the most common causes of oral pigmentation is smoker melanosis, a condition associated with the melanocyte stimulation caused by cigarette smoke. This paper aims to illustrate the use of a carbon dioxide laser in the removal of the gingival melanic pigmentation for aesthetic reasons in a 27-year-old female patient with history of a smoking habit. The carbon dioxide laser vaporisation was performed on the gingival mucosa with effective and quick results and without any complications or significant symptoms after the treatment. We conclude that a carbon dioxide laser could be a useful, effective, and safe instrument to treat the aesthetic complications caused by oral smoker melanosis.
Severe Psychotic Disorder as the Main Manifestation of Adrenal Insufficiency
Authors: Farah Julia de Lima , Lauand Carolina Villar , Chequi Lucas , Fortunato Enrico , Pasqualino Felipe , Bignotto Luis Henrique , Batista Rafael Loch , Aprahamian Ivan
Published: April 2015

We describe a case of severe psychotic disorder as the only manifestation of primary adrenal insufficiency. A 63-year-old man presented with psychotic symptoms without any prior psychiatric history. During the clinical and laboratorial investigation, exams revealed a normovolemic hyponatremia. The patient showed no other clinical signs or symptoms compatible with adrenal insufficiency but displayed very high ACTH and low serum cortisol concentrations. Brain magnetic resonance imaging showed no significant changes, including the pituitary gland. The patient was initially treated with intravenous corticosteroids, resulting in rapid remission of the psychotic symptoms. The association between adrenal insufficiency and neuropsychiatric symptoms is rare but these symptoms can often be the first clinical presentation of the disease.
Anomaly Detection and Degradation Prediction of MOSFET
Authors: Wu Li-Feng , Guan Yong , Li Xiao-Juan , Ma Jie
Published: April 2015

The MOSFET is an important power electronic transistor widely used in electrical systems. Its reliability has an effect on the performance of systems. In this paper, the failure models and mechanisms of MOSFETs are briefly analyzed. The on-resistanceRonis the key failure precursor parameter representing the degree of degradation. Based on the experimental data, a nonlinear dual-exponential degradation model for MOSFETs is obtained. Then, we present an approach for MOSFET degradation state prediction using a strong tract filter based on the obtained degradation model. Lastly, the proposed algorithm is shown to perform effectively on experimental data. Thus, it can provide early warning and enhance the reliability of electrical systems.
Efficient Pairing-Free Privacy-Preserving Auditing Scheme for Cloud Storage in Distributed Sensor Networks
Authors: Zhang Xinpeng , Xu Chunxiang , Zhang Xiaojun
Published: April 2015

With the rapid growth of the distributed sensor networks, the distributed sensor network data security problems begin to attract the attention of people. The previous research of distributed sensor network security has focused on secure information in communication; however the research of secure data storage has been overlooked. As we know, cloud data storage and retrieval have become popular for efficient data management in distributed sensor networks; thus they can enjoy the on-demand high-quality cloud storage service. Meanwhile, it also introduces new security challenges. To tackle with these security challenges, many classic auditing schemes of cloud storage have been proposed. However, these schemes all need very expensive pairing computation, which is not suitable for sensor networks. In this paper, we propose an efficient pairing-free auditing scheme for data storage of distributed sensor networks. We exploit homomorphic message authentication codes (MACs) to reduce the space used to store the verification information. We also employ the random masking technique to make sure the TPA cannot recover the primitive data blocks of the sensor networks data manager. Experimental results show that our auditing scheme is more light-weight than previous auditing schemes and more practical in applied distributed sensor networks environments.
Nurse Scheduling with Joint Normalized Shift and Day-Off Preference Satisfaction Using a Genetic Algorithm with Immigrant Scheme
Authors: Lin Chun-Cheng , Kang Jia-Rong , Chiang Ding-Jung , Chen Chien-Liang
Published: April 2015

To make a fair and satisfactory nurse shift schedule, this paper proposes a novel preference satisfaction function, in which numbers of the preferred work shifts and days-off of the nursing staff are balanced, and ranks for preferences and number of the preference ranks satisfied so far are also considered. Such a preference function is capable of equivalently and fairly planning the nurse preference schedule to improve the total satisfaction. Additionally, distributed sensors can be applied to collect the information on hospital beds to provide the schedule planner to determine the lowest required amount of manpower for each work shift, to avoid the working overload of the nursing staff. To solve the nursing schedule problem, we propose a genetic algorithm (GA) with an immigrant scheme, in which utilization of the immigrant scheme is helpful in efficiently reducing amount of infeasible solutions due to practical scheduling constraints, so that the GA can efficiently find better solutions for larger-scale problems. Performance of the proposed GA with and without solution recovery scheme is evaluated by conducting a comprehensive experimental analysis on three different-size instances.
Simple Lymphangioma to Generalized Lymphatic Anomaly: Role of Imaging in Disclosure of a Rare and Morbid Disease
Authors: Joshi Manoj , Phansalkar Dilip S.
Published: April 2015

Generalized lymphatic anomaly is a rare multisystem congenital disorder in which multiple organs are involved. Imaging features often overlap with other complex lymphatic anomalies and diagnosis is difficult. Treatment options are limited, not remedial and prognosis is poor. We report a 12-year-old male who presented with axillary and chest wall lymphangioma but was subsequently diagnosed as having diffuse lymphangiomatosis affecting lungs, liver, spleen, and bones on computerized tomography scan. We suggest complete radiological evaluation of susceptible adolescent children with lymphangioma to avoid diagnostic delay in this morbid condition. We also discuss radiological features of other similar complex lymphatic anomalies and crucial role of imaging in diagnosis.
A Column Generation Based Hyper-Heuristic to the Bus Driver Scheduling Problem
Authors: Li Hong , Wang Ying , Li Shi , Li Sujian
Published: April 2015

Public transit providers are facing continuous pressure to improve service quality and reduce operating costs. Bus driver scheduling is among the most studied problems in this area. Based on this, flexible and powerful optimization algorithms have thus been developed and used for many years to help them with this challenge. Particularly, real-life large and complex problem instances often need new approaches to overcome the computational difficulties in solving them. Thus, we propose a column generation based hyper-heuristic for finding near-optimal solutions. Our approach takes advantages of the benefits offered by heuristic method since the column selection mode is driven by a hyper-heuristic using various strategies for the column generation subproblem. The performance of the proposed algorithm is compared with the approaches in the literature. Computational results on real-life instances are presented and discussed.
Spatiotemporal Variation and Abrupt Change Analysis of Temperature from 1960 to 2012 in the Huang-Huai-Hai Plain, China
Authors: Yin Yanyu , Liu Hui , Yi Xiangsheng , Liu Weidong
Published: April 2015

Based on a monthly dataset of temperature time series (1960–2012) in the Huang-Huai-Hai Plain of China (HHHPC), spatiotemporal variation and abrupt change analysis of temperature were examined by moving average, linear regression, spline interpolation, Mann-Kendall test, and movingt-test. Major conclusions were listed as follows. (1) Annual and seasonal temperature increased with different rates on the process of fluctuating changes during 1960~2012. The upward trend was 0.22°C 10a−1for annual temperature, while it was very significant in winter (0.34°C 10a−1) and spring (0.31°C 10a−1), moderately significant in autumn (0.21°C 10a−1), and nonsignificant in summer (0.05°C 10a−1). (2) The spatial changes of annual and seasonal temperature were similar. The temperature increased significantly in Beijing and its adjacent regions, while it was nonsignificant in the central and southern regions. (3) The spring, autumn, winter, and annual temperature had warm abrupt change. The abrupt change time for winter temperature was in the late 1970s, while it was in the late 1980s and early 1990s for spring, autumn, and annual temperature. (4) Macroscopic effects of global and regional climate warming and human activities were probably responsible for the temperature changes. The climate warming would influence the hydrological cycle and agricultural crops in the study area.
Chitosan Prevents Gentamicin-Induced Nephrotoxicity via a Carbonyl Stress-Dependent Pathway
Authors: Chou Chu-Kung , Li Yi-Chieh , Chen Shih-Ming , Shih Yi-Min , Lee Jen-Ai
Published: April 2015

Aminoglycosides are widely used to treat infections; however, their applications are limited by nephrotoxicity. With the increase of antibiotic resistance, the use of aminoglycosides is inevitable. Low-molecular-weight chitosan (LMWC) has shown renal protective effects in dialysis patients. However, no study has evaluated LMWC for preventing aminoglycoside-induced nephrotoxicity or determined the mechanisms underlying the renal protective effects. In this study, LMWC (165 or 825 mg/kg/day) or metformin (100 mg/kg/day) was orally administered for 13 days to rats with nephropathy induced by gentamicin (GM), a kind of aminoglycoside (150 mg/kg/day i.p. for 6 days). Both LMCW doses improved renal function. Serum creatinine levels improved in rats treated with 165 and 825 mg/kg/day LMWC (from 2.14 ± 0.74 mg/dL to 1.26 ± 0.46 mg/dL and 0.69 ± 0.12 mg/dL, resp.,P< 0.05). Blood urea nitrogen levels were also improved in these rats (from 73.73 ± 21.13 mg/dL to 58.70 ± 22.71 mg/dL and 28.82 ± 3.84 mg/dL, resp.,P< 0.05). Additionally, renal tissue morphology improved after LMWC treatment, and accumulation of renal methylglyoxal, a damage factor associated with carbonyl stress, was reversed. These results show that LMWC prevents GM-induced renal toxicity via a carbonyl stress-dependent pathway.
Introduction of Auricular Acupuncture in Elderly Patients Suffering from Major Depression: Protocol of a Mixed Methods Feasibility Study
Authors: Geib Janina , Rieger Monika A. , Joos Stefanie , Eschweiler Gerhard W. , Dresler Thomas , Metzger Florian G.
Published: April 2015

Background. Due to an increasing number of elderly people suffering from major depression and potential side effects of the prescribed drugs, the introduction of new therapeutic approaches is needed. Currently, in Germany, auricular acupuncture is no part of clinical care for gerontopsychiatric patients. Based on promising clinical experiences and existing evidence for treating addiction and trauma, a benefit of auricular acupuncture integrated in existing treatment programs in elderly patients may be hypothesized. Within this project auricular acupuncture according to the National Acupuncture Detoxification Association (NADA) will be integrated in the multimodal treatment regime for elderly patients with major depression in a daytime ward setting.Methods/Design. To evaluate the feasibility and acceptance a mixed method approach is used. In a day clinic, a sample of 20 psychogeriatric patients with the diagnosis of major depression will be enrolled. The patients will receive a total of nine auricular acupuncture treatments according to the standardized NADA protocol in a group setting. The therapeutic process, its organization, the experience, and the willingness of patients to participate will be evaluated by interviews with patients and the therapeutic team. Data will be analyzed qualitatively using content analysis. Additionally, quantitative outcome parameters will be measured by standardized questionnaires.
A Single-Machine Two-Agent Scheduling Problem by a Branch-and-Bound and Three Simulated Annealing Algorithms
Authors: Liu Shangchia , Wu Wen-Hsiang , Kang Chao-Chung , Lin Win-Chin , Cheng Zhenmin
Published: April 2015

In the field of distributed decision making, different agents share a common processing resource, and each agent wants to minimize a cost function depending on its jobs only. These issues arise in different application contexts, including real-time systems, integrated service networks, industrial districts, and telecommunication systems. Motivated by its importance on practical applications, we consider two-agent scheduling on a single machine where the objective is to minimize the total completion time of the jobs of the first agent with the restriction that an upper bound is allowed the total completion time of the jobs for the second agent. For solving the proposed problem, a branch-and-bound and three simulated annealing algorithms are developed for the optimal solution, respectively. In addition, the extensive computational experiments are also conducted to test the performance of the algorithms.
Head-Neck Taper Corrosion in Hip Arthroplasty
Authors: Hussenbocus S. , Kosuge D. , Solomon L. B. , Howie D. W. , Oskouei R. H.
Published: April 2015

Modularity at the head-neck junction of the femoral component in THA became popular as a design feature with advantages of decreasing implant inventory and allowing adjustment of leg length, offset, and soft tissue balancing through different head options. The introduction of a new modular interface to femoral stems that were previously monoblock, or nonmodular, comes with the potential for corrosion at the taper junction through mechanically assisted crevice corrosion. The incidence of revision hip arthroplasty is on the rise and along with improved wear properties of polyethylene and ceramic, use of larger femoral head sizes is becoming increasingly popular. Taper corrosion appears to be related to all of its geometric parameters, material combinations, and femoral head size. This review article discusses the pathogenesis, risk factors, clinical assessment, and management of taper corrosion at the head-neck junction.
The Role of IL‐1β in the Bone Loss during Rheumatic Diseases
Authors: Ruscitti Piero , Cipriani Paola , Carubbi Francesco , Liakouli Vasiliki , Zazzeroni Francesca , Di Benedetto Paola , Berardicurti Onorina , Alesse Edoardo , Giacomelli Roberto
Published: April 2015

Several inflammatory diseases have been associated with increased bone resorption and fracture rates and different studies supported the relation between inflammatory cytokines and osteoclast activity. The main factor required for osteoclast activation is the stimulation by receptor activator of nuclear factor kappa‐B ligand (RANKL) expressed on osteoblasts. In this context, interleukin‐ (IL‐) 1β, one of the most powerful proinflammatory cytokines, is a strong stimulator of in vitro and in vivo bone resorption via upregulation of RANKL that stimulates the osteoclastogenesis. The resulting effects lead to an imbalance in bone metabolism favouring bone resorption and osteoporosis. In this paper, we review the available literature on the role of IL‐1β in the pathogenesis of bone loss. Furthermore, we analysed the role of IL‐1β in bone resorption during rheumatic diseases and, when available, we reported the efficacy of anti‐IL‐1β therapy in this field.
Online Scheduling on a Single Machine with Grouped Processing Times
Authors: Liu Qijia , Wan Long , Wei Lijun
Published: April 2015

We consider the online scheduling problem on a single machine with the assumption that all jobs have their processing times in[p,(1+α)p], wherep>0andα=(5-1)/2. All jobs arrive over time, and each job and its processing time become known at its arrival time. The jobs should be first processed on a single machine and then delivered by a vehicle to some customer. When the capacity of the vehicle is infinite, we provide an online algorithm with the best competitive ratio of(5+1)/2. When the capacity of the vehicle is finite, that is, the vehicle can deliver at mostcjobs at a time, we provide another best possible online algorithm with the competitive ratio of(5+1)/2.
Ferroelectric Polymer Thin Films for Organic Electronics
Authors: Mai Manfang , Ke Shanming , Lin Peng , Zeng Xierong
Published: April 2015

The considerable investigations of ferroelectric polymer thin films have explored new functional devices for flexible electronics industry. Polyvinylidene fluoride (PVDF) and its copolymer with trifluoroethylene (TrFE) are the most commonly used polymer ferroelectric due to their well‐defined ferroelectric properties and ease of fabrication into thin films. In this study, we review the recent advances of thin ferroelectric polymer films for organic electronic applications. Initially the properties of ferroelectric polymer and fabrication methods of thin films are briefly described. Then the theoretical polarization switching models for ferroelectric polymer films are summarized and the switching mechanisms are discussed. Lastly the emerging ferroelectric devices based on P(VDF‐TrFE) films are addressed. Conclusions are drawn regarding future work on materials and devices.
A Silent Alarm at Occupational Evaluation Two Months after a Normal Painful ECG: A Case of Wellens’ syndrome
Authors: Di Stolfo Giuseppe , Mastroianno Sandra , De Luca Giovanni , Potenza Domenico Rosario , Marchese Nicola , Vigna Carlo , Fanelli Raffaele
Published: April 2015

We describe a case of a 42-year-old man, with a previous episode of angina and a normal ECG and serum cardiac markers, and a two months later finding of biphasic T wave in leads V2-V3 and deeply inverted T wave in V4-V5 at a asymptomatic occupational evaluation. This is a typical ECG pattern of Wellens’ syndrome. A subsequent coronary angiography showed a critical stenosis of proximal left anterior descendent. We underline the careful value of prolonged observation in chest pain unit and repetitive ECG evaluation also during pain-free period after an angina episode, to exclude an earlier T wave pseudonormalization.
A Hybrid Heuristic Algorithm for Ship Block Construction Space Scheduling Problem
Authors: Hu Shicheng , Liu Tengjiao , Wang Song , Kao Yonggui , Sun Xuedong
Published: April 2015

Ship block construction space is an important bottleneck resource in the process of shipbuilding, so the production scheduling optimization is a key technology to improve the efficiency of shipbuilding. With respect to ship block construction space scheduling problem, a hybrid heuristic algorithm is proposed in this paper. Firstly, Bottom-Left-Fill (BLF) process is introduced. Next, an initial solution is obtained by guiding the sorting process with corners. Then on the basis of the initial solution, the simulated annealing arithmetic (SA) is used to improve the solution by offering a possibility to accept worse neighbor solutions in order to escape from local optimum. Finally, the simulation experiments are conducted to verify the effectiveness of the algorithm.
Biomechanical Stability of Dental Implants in Augmented Maxillary Sites: Results of a Randomized Clinical Study with Four Different Biomaterials and PRF and a Biological View on Guided Bone Regeneration
Authors: Angelo Troedhan , Marcel Wainwright , Andreas Kurrek , Izabela Schlichting
Published: April 2015

Introduction. Bone regenerates mainly by periosteal and endosteal humoral and cellular activity, which is given only little concern in surgical techniques and choice of bone grafts for guided bone regeneration. This study investigates on a clinical level the biomechanical stability of augmented sites in maxillary bone when a new class of moldable, self-hardening calcium-phosphate biomaterials (SHB) is used with and without the addition of Platelet Rich Fibrin (aPRF) in the Piezotome-enhanced subperiosteal tunnel-technique (PeSPTT).Material and Methods. 82 patients with horizontal atrophy of anterior maxillary crest were treated with PeSPTT and randomly assigned biphasic (60% HA/40% bTCP) or monophasic (100% bTCP) SHB without or with addition of aPRF. 109 implants were inserted into the augmented sites after 8.3 months and the insertion-torque-value (ITV) measured as clinical expression of the (bio)mechanical stability of the augmented bone and compared to ITVs of a prior study in sinus lifting.Results. Significant better results of (bio)mechanical stability almost by two-fold, expressed by higher ITVs compared to native bone, were achieved with the used biomaterials and more constant results with the addition of aPRF.Conclusion. The use of SHB alone or combined with aPRF seems to be favourable to achieve a superior (bio)mechanical stable restored alveolar bone.
Recognition and Empirical Research on Key Influencing Factors of Low Carbon Development for Logistics Company
Authors: Duan Xiang-Yun , Chou Hsiu-Jung , Cheng Shuenn-Ren
Published: April 2015

The questionnaire paper used was work out by modifying the existing mature research scale and interviewing the experts and enterprises. The purpose of this study is to explore the key influencing factors of low carbon development for logistics companies by using the data from the questionnaire, which might contribute to further investigation of low carbon development pathway. Through correlation and stepwise regression analysis, differences between influencing factors and impact-degree were found since specific environmental behaviors of low carbon logistics might vary significantly. The driving factor of low carbon input comes from external points such as government and public external pressure, so the low carbon input is driven by an outside force. Yet, low carbon operation is significantly affected by internal factors such as low carbon behavior capacity, which is driven by an inside force.
Neuroinvasive Cryptococcosis in an Immunocompetent Patient with a Negative Spinal FluidCryptococcusAntigen
Authors: Garcia-Santibanez Rocio C. , Gill Veenu , Yancovitz Stanley , Pyburn DeWitt
Published: April 2015

58-year-old man presented with headache, nausea, vomiting, and gait disturbance. Brain MRI showed meningeal enhancement and herniation. SerumCryptococcusantigen was positive but spinal fluid antigen and cultures were negative. A cerebellar biopsy revealed nonencapsulatedCryptococcus. He completed antifungal therapy. SerumCryptococcusantigen titer decreased. He had a full neurological recovery.
Repeat Upper Gastrointestinal Endoscopy in Patients with Functional Dyspepsia: Yield, Findings, and Predictors of Positive Findings
Authors: Pongprasobchai Supot , Asanaleykha Natta , Tantayakom Pongchirat
Published: April 2015

Background. No guideline on repeat esophagogastroduodenoscopy (EGD) in functional dyspepsia (FD) exists. This study aimed to define yield, findings, and predictors of positive findings on repeat EGD in FD.Methods. FD patients who underwent at least 2 EGDs during October 2005 to November 2011 were enrolled and reviewed. Yield and findings were analyzed and univariate and multivariate analyses were performed to identify predictors of positive repeat EGD.Results. The median time to repeat EGD was 34 months. Among 146 patients, 115 patients (79%) had negative and 31 (21%) had positive repeat EGD, including erosive gastritis (13.0%), peptic ulcer (7.5%), reflux esophagitis (1.4%), and Barrett’s esophagus (0.7%). Four independent predictors of positive repeat EGD were smoking (HR 3.88, 95% CI 1.31–11.51,P=0.015), hypertension (HR 2.96, 95% CI 1.38–6.36,P=0.050), history of malignancies (HR 3.65, 95% CI 1.16–11.46,P=0.027), and antiplatelets or NSAIDs used within 4 weeks (HR 4.10, 95% CI 1.13–14.90,P=0.032), while alarm features or failure to treatment did not predict positive repeat EGD.  Conclusion. Yield of repeat EGD in FD was substantially low, all findings were acid-related disorders, and there was no malignancy. Smoking, hypertension, history of malignancies, and antiplatelets/NSAIDs use associated with positive repeat EGD.
The Effect of Ginger (Zingiber officinalis) and Artichoke (Cynara cardunculus) Extract Supplementation on Functional Dyspepsia: A Randomised, Double-Blind, and Placebo-Controlled Clinical Trial
Authors: Giacosa Attilio , Guido Davide , Grassi Mario , Riva Antonella , Morazzoni Paolo , Bombardelli Ezio , Perna Simone , Faliva Milena A. , Rondanelli Mariangela
Published: April 2015

Objective.Functional dyspepsia (FD) is a frequent clinical finding in western world. The aim of this study is to compare the efficacy of a ginger and artichoke supplementation versus placebo in the treatment of FD.Methods.A prospective multicentre, double blind, randomized, placebo controlled, parallel-group comparison of the supplement and placebo over a period of 4 weeks was performed. Two capsules/day were supplied (before lunch and dinner) to 126 FD patients (supplementation/placebo: 65/61).Results. After 14 days of treatment, only supplementation group (SG) showed a significant amelioration (SG:αS=+1.195MCA score units (u),P=0.017; placebo:αP=+0.347 u,P=0.513). The intercept (α) resulted to be significantly higher in SG than in placebo (αS-αP=+0.848 u,P<0.001). At the end of the study, the advantage of SG versus placebo persists without variation (βS-βP=+0.077 u,P=0.542). In SG, a significant advantage is observed for nausea (βS-βP=-0.398 u,P<0.001), epigastric fullness (βS-βP=-0.241,P<0.001), epigastric pain (βS-βP=-0.173 u,P=0.002), and bloating (βS-βP=-0.167 u,P=0.017).Conclusions. The association between ginger and artichoke leaf extracts appears safe and efficacious in the treatment of FD and could represent a promising treatment for this disease.
The Relationship between Anterior Cruciate Ligament Injury and Osteoarthritis of the Knee
Authors: Simon David , Mascarenhas Randy , Saltzman Bryan M. , Rollins Meaghan , Bach Bernard R. , MacDonald Peter
Published: April 2015

Anterior cruciate ligament (ACL) tears are a common injury, particularly in the athletic and youth populations. The known association between ACL injury and subsequent osteoarthritis (OA) of the knee merits a more in-depth understanding of the relationship between the ACL-injured knee and osteoarthritis. ACL injury, especially with concomitant meniscal or other ligamentous pathology, predisposes the knee to an increased risk of osteoarthritis. ACL insufficiency results in deterioration of the normal physiologic knee bending culminating in increased anterior tibial translation and increased internal tibial rotation. This leads to increased mean contact stresses in the posterior medial and lateral compartments under anterior and rotational loading. However, surgical reconstruction of the ACL has not been shown to reduce the risk of future OA development back to baseline and has variability based on operative factors of graft choice, timing of surgery, presence of meniscal and chondral abnormalities, and surgical technique. Known strategies to prevent OA development are applicable to patients with ACL deficiency or after ACL reconstruction and include weight management, avoidance of excessive musculoskeletal loading, and strength training. Reconstruction of the ACL does not necessarily prevent osteoarthritis in many of these patients and may depend on several external variables.
Differential Effects of Endotracheal Suctioning on Gas Exchanges in Patients with Acute Respiratory Failure under Pressure-Controlled and Volume-Controlled Ventilation
Authors: Liu Xiao-Wei , Jin Yan , Ma Tao , Qu Bo , Liu Zhi
Published: April 2015

This study was conducted to evaluate the effects of open endotracheal suctioning on gas exchange and respiratory mechanics in ARF patients under the modes of PCV or VCV. Ninety-six ARF patients were treated with open endotracheal suctioning and their variations in respiratory mechanics and gas exchange after the suctions were compared. Under PCV mode, compared with the initial level of tidal volume (VT), ARF patients showed 30.0% and 27.8% decrease at 1 min and 10 min, respectively. Furthermore, the initial respiratory system compliance (Crs) decreased by 29.6% and 28.5% at 1 min and 10 min, respectively. Under VCV mode, compared with the initial level, 38.6% and 37.5% increase in peak airway pressure (PAP) were found at 1 min and 10 min, respectively. Under PCV mode, the initial PaO2increased by 6.4% and 10.2 % at 3 min and 10 min, respectively, while 18.9% and 30.6% increase of the initial PaO2were observed under VCV mode. Summarily, endotracheal suctioning may impair gas exchange and decrease lung compliance in ARF patients receiving mechanical ventilation under both PCV and VCV modes, but endotracheal suctioning effects on gas exchange were more severe and longer-lasting under PCV mode than VCV.
Neonatal Urinary Ascites: A Report of Three Cases
Authors: Solarin Adaobi , Gajjar Priya , Nourse Peter
Published: April 2015

Urinary ascites in neonates is not a common condition. Three cases of urinary ascites are presented and each of them has a different aetiology. Neonates with urinary ascites usually present as clinical emergency, requiring resuscitation, ventilator support, and subsequent drainage of urine. The ultimate management depends on the site of extravasation and the underlying cause.
Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models
Authors: Eberlein Catherine A. , Stetson Daniel , Markovets Aleksandra A. , Al-Kadhimi Katherine J. , Lai Zhongwu , Fisher Paul R. , Meador Catherine B. , Spitzler Paula , Ichihara Eiki , Ross Sarah J. , Ahdesmaki Miika J. , Ahmed Ambar , Ratcliffe Laura E. , O'Brien Elizabeth L. Christey , Barnes Claire H. , Brown Henry , Smith Paul D. , Dry Jonathan R. , Beran Garry , Thress Kenneth S. , Dougherty Brian , Pao William , Cross Darren A.E.
Published: April 2015

Resistance to targeted EGFR inhibitors is likely to develop in EGFR-mutant lung cancers. Early identification of innate or acquired resistance mechanisms to these agents is essential to direct development of future therapies. We describe the detection of heterogeneous mechanisms of resistance within populations of EGFR-mutant cells (PC9 and/or NCI-H1975) with acquired resistance to current and newly developed EGFR tyrosine kinase inhibitors, including AZD9291. We report the detection of NRAS mutations, including a novel E63K mutation, and a gain of copy number of WT NRAS or WT KRAS in cell populations resistant to gefitinib, afatinib, WZ4002, or AZD9291. Compared with parental cells, a number of resistant cell populations were more sensitive to inhibition by the MEK inhibitor selumetinib (AZD6244; ARRY-142886) when treated in combination with the originating EGFR inhibitor. In vitro, a combination of AZD9291 with selumetinib prevented emergence of resistance in PC9 cells and delayed resistance in NCI-H1975 cells. In vivo, concomitant dosing of AZD9291 with selumetinib caused regression of AZD9291-resistant tumors in an EGFRm/T790M transgenic model. Our data support the use of a combination of AZD9291 with a MEK inhibitor to delay or prevent resistance to AZD9291 in EGFRm and/or EGFRm/T790M tumors. Furthermore, these findings suggest that NRAS modifications in tumor samples from patients who have progressed on current or EGFR inhibitors in development may support subsequent treatment with a combination of EGFR and MEK inhibition. Cancer Res; 75(12); 2489–500. ©2015 AACR.
A New B7:CD28 Family Checkpoint Target for Cancer Immunotherapy: HHLA2
Authors: Xiao Yanping , Freeman Gordon J.
Published: April 2015

HHLA2 is a newly identified B7 family member that modulates T-cell functions through interaction with TMIGD2 and possibly a second receptor, with coinhibition in two studies and costimulation in one study. HHLA2 is expressed on a variety of human cancers, and its coinhibitory function makes it a candidate for cancer immunotherapy. Clin Cancer Res; 21(10); 2201–3. ©2015 AACR.

See related article by Janakiram et al., p. 2359
Ablative Tumor Radiation Can Change the Tumor Immune Cell Microenvironment to Induce Durable Complete Remissions
Authors: Filatenkov Alexander , Baker Jeanette , Mueller Antonia M.S. , Kenkel Justin , Ahn G-One , Dutt Suparna , Zhang Nigel , Kohrt Holbrook , Jensen Kent , Dejbakhsh-Jones Sussan , Shizuru Judith A. , Negrin Robert N. , Engleman Edgar G. , Strober Samuel
Published: April 2015

Purpose: The goals of the study were to elucidate the immune mechanisms that contribute to desirable complete remissions of murine colon tumors treated with single radiation dose of 30 Gy. This dose is at the upper end of the ablative range used clinically to treat advanced or metastatic colorectal, liver, and non–small cell lung tumors.

Experimental Design: Changes in the tumor immune microenvironment of single tumor nodules exposed to radiation were studied using 21-day (>1 cm in diameter) CT26 and MC38 colon tumors. These are well-characterized weakly immunogenic tumors.

Results: We found that the high-dose radiation transformed the immunosuppressive tumor microenvironment resulting in an intense CD8+ T-cell tumor infiltrate, and a loss of myeloid-derived suppressor cells (MDSC). The change was dependent on antigen cross-presenting CD8+ dendritic cells, secretion of IFNγ, and CD4+T cells expressing CD40L. Antitumor CD8+ T cells entered tumors shortly after radiotherapy, reversed MDSC infiltration, and mediated durable remissions in an IFNγ-dependent manner. Interestingly, extended fractionated radiation regimen did not result in robust CD8+ T-cell infiltration.

Conclusions: For immunologically sensitive tumors, these results indicate that remissions induced by a short course of high-dose radiotherapy depend on the development of antitumor immunity that is reflected by the nature and kinetics of changes induced in the tumor cell microenvironment. These results suggest that systematic examination of the tumor immune microenvironment may help in optimizing the radiation regimen used to treat tumors by adding a robust immune response. Clin Cancer Res; 21(16); 3727–39. ©2015 AACR.
The Prognostic Impact of CD163-Positive Macrophages in Follicular Lymphoma: A Study from the BC Cancer Agency and the Lymphoma Study Association
Authors: Kridel Robert , Xerri Luc , Gelas-Dore Bénédicte , Tan King , Feugier Pierre , Vawda Ayesha , Canioni Danielle , Farinha Pedro , Boussetta Sami , Moccia Alden A. , Brice Pauline , Chavez Elizabeth A. , Kyle Alastair H. , Scott David W. , Sanders Ashley D. , Fabiani Bettina , Slack Graham W. , Minchinton Andrew I. , Haioun Corinne , Connors Joseph M. , Sehn Laurie H. , Steidl Christian , Gascoyne Randy D. , Salles Gilles
Published: April 2015

Purpose: We aimed to assess the prognostic significance of follicular lymphoma–associated macrophages in the era of rituximab treatment and maintenance.

Experimental Design: We applied immunohistochemistry for CD68 and CD163 to two large tissue microarrays (TMA). The first TMA included samples from 186 patients from the BC Cancer Agency (BCCA) who had been treated with first-line systemic treatment including rituximab, cyclophosphamide, vincristine, and prednisone. The second contained 395 samples from PRIMA trial patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and randomized to rituximab maintenance or observation. Macrophage infiltration was assessed using Aperio image analysis. Each of the two cohorts was randomly split into training/validation sets.

Results: An increased CD163-positive pixel count was predictive of adverse outcome in the BCCA dataset [5-year progression-free survival (PFS) 38% vs. 72%, respectively, P = 0.004 in the training cohort and 5-year PFS 29% vs. 61%, respectively, P = 0.004 in the validation cohort]. In the PRIMA trial, an increased CD163 pixel count was associated with favorable outcome (5-year PFS 60% vs. 44%, respectively, P = 0.011 in the training cohort and 5-year PFS 55% vs. 37%, respectively, P = 0.030 in the validation cohort).

Conclusions: CD163-positive macrophages predict outcome in follicular lymphoma, but their prognostic impact is highly dependent on treatment received. Clin Cancer Res; 21(15); 3428–35. ©2015 AACR.
Remyelination by Resident Oligodendrocyte Precursor Cells in a Xenopus laevis Inducible Model of Demyelination
Authors: Sekizar Sowmya , Mannioui Abdelkrim , Azoyan Loris , Colin Catherine , Thomas Jean-Léon , Du Pasquier David , Mallat Michel , Zalc Bernard
Published: April 2015

We have generated a Xenopus laevis transgenic line, MBP-GFP-NTR, allowing conditional ablation of myelin-forming oligodendrocytes. In this transgenic line the transgene is driven by the proximal portion of the myelin basic protein regulatory sequence, specific to mature oligodendrocytes. The transgene protein is formed by the green fluorescent protein reporter fused to the Escherichia coli nitroreductase (NTR) selection enzyme. The NTR enzyme converts the innocuous prodrug metronidazole (MTZ) to a cytotoxin. Ablation of oligodendrocytes by MTZ treatment of the tadpole induced demyelination, and here we show that myelin debris are subsequently eliminated by microglial cells. After cessation of MTZ treatment, remyelination proceeded spontaneously. We questioned the origin of remyelinating cells. Our data suggest that Sox10+ oligodendrocyte precursor cells (OPCs), which are already present in the optic nerve prior to the experimentally induced demyelination, are responsible for remyelination, and this required only minimal (if any) cell division of OPCs.
Role of Host-Derived Proteinases in Dentine Caries and Erosion
Authors: Buzalaf Marília Afonso Rabelo , Charone Senda , Tjäderhane Leo
Published: April 2015

Demineralization in dentinal caries and erosion exposes dentine organic matrix. This exposed matrix, containing type I collagen and non-collagenous proteins, is then degraded by host collagenolytic enzymes, matrix metalloproteinases (MMPs) and cysteine cathepsins. The knowledge of the identities and function of these enzymes in dentine has accumulated only within the last 15 years, but has already formed a field of research called ‘dentine degradomics'. This research has demonstrated the role of endogenous collagenolytic enzymes in caries and erosion development. In demineralized dentine, the enzymes degrade triple-helical collagen molecules, leading to the gradual loss of collagen matrix. Even before that, they can cleave off the terminal non-helical ends of collagen molecules called telopeptides, leading to the structural changes at the intramolecular gap areas, which may affect or even prevent intrafibrillar remineralization, which is considered essential in restoring the dentine's mechanical properties. They may also cause the loss of non-collagenous proteins that could serve as nucleation sites for remineralization. Here we review the findings demonstrating that inhibition of salivary or dentine endogenous MMPs and cysteine cathepsins may provide preventive means against the progression of caries or erosion. Furthermore, we also suggest the future directions for the new experimental preventive research to gain more knowledge of the enzymes and their function during and after dentine demineralization, and the pathways to find the clinically acceptable means to prevent the functional activity of these enzymes.
The Future of Fluorides and Other Protective Agents in Erosion Prevention
Authors: Lussi Adrian , Carvalho Thiago Saads
Published: April 2015

The effectiveness of fluoride in caries prevention has been convincingly proven. In recent years, researchers have investigated the preventive effects of different fluoride formulations on erosive tooth wear with positive results, but their action on caries and erosion prevention must be based on different requirements, because there is no sheltered area in the erosive process as there is in the subsurface carious lesions. Thus, any protective mechanism from fluoride concerning erosion is limited to the surface or the near surface layer of enamel. However, reports on other protective agents show superior preventive results. The mechanism of action of tin-containing products is related to tin deposition onto the tooth surface, as well as the incorporation of tin into the near-surface layer of enamel. These tin-rich deposits are less susceptible to dissolution and may result in enhanced protection of the underlying tooth. Titanium tetrafluoride forms a protective layer on the tooth surface. It is believed that this layer is made up of hydrated hydrogen titanium phosphate. Products containing phosphates and/or proteins may adsorb either to the pellicle, rendering it more protective against demineralization, or directly to the dental hard tissue, probably competing with H+ at specific sites on the tooth surface. Other substances may further enhance precipitation of calcium phosphates on the enamel surface, protecting it from additional acid impacts. Hence, the future of fluoride alone in erosion prevention looks grim, but the combination of fluoride with protective agents, such as polyvalent metal ions and some polymers, has much brighter prospects.
Allogeneic Hematopoietic Stem Cell Transplantation in Mantle Cell Lymphoma: A Retrospective Analysis of 7 Patients
Authors: Lamm Wolfgang , Wohlfarth Philipp , Bojic Marija , Schörgenhofer Christian , Kalhs Peter , Raderer Markus , Rabitsch Werner
Published: April 2015

Mantle cell lymphoma (MCL) is a B cell non-Hodgkin's lymphoma characterized by a poor prognosis. Many different therapeutic approaches including intensive chemotherapy as well as new targeted therapies are established. However, overall survival remains unsatisfying. As the sole curative option, allogeneic hematopoietic stem cell transplantation (HSCT) has been described, but only a limited number of patients qualify for this procedure. We have retrospectively analyzed 7 patients with stage IV MCL undergoing allogeneic HSCT at our institution. A myeloablative regimen was used in 1 patient, while the other 6 patients received reduced-intensity conditioning. Four patients had an HLA-identical sibling, and the remaining 3 patients had an HLA-identical unrelated donor. One patient developed acute graft-versus-host disease (skin, grade III; intestine, grade II). Two patients died from transplant-related causes, 3 patients died due to progressive disease and the remaining 2 patients are still in complete remission 147 and 8 months after transplantation. Allogeneic HSCT offers a therapeutic treatment option for selected patients in a relapsed/refractory setting. The incorporation of novel agents has improved the outcome of patients with MCL. Thus, the role and optimal time point of allogeneic HSCT should be reevaluated in randomized trials.