bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic parameters of milk cholesterol content in Holstein cattle
Authors: Do Duy N. , Fleming Allison , Schenkel Flavio S. , Miglior Filippo , Zhao Xin , Ibeagha-Awemu Eveline M.
Published: April 2018

This study aimed to estimate heritability for milk cholesterol (CHL) and genetic correlations between milk CHL and other production traits (test-day milk, fat, and protein yields, fat and protein percentages, and somatic cell score). Milk CHL content was determined by gas chromatography and expressed as mg of CHL in 100 g of fat (CHL_fat) or in 100 mg of milk (CHL_milk). Univariate models were used to estimate variances and heritability, whereas bivariate models were used to compute correlations using data from 1793 cows. The average concentrations (standard deviation) of CHL_fat and CHL_milk were 275.63 (75) mg and 11.16 (3.63) mg, respectively. Milk CHL content was significantly affected by days in milk and herd (P < 0.05), but not by parity, regardless of the scale of expression. Heritability estimates for CHL_fat and CHL_milk were 0.06 ± 0.04 and 0.17 ± 0.06, respectively. Phenotypic and genetic correlations between CHL_fat and CHL_milk were 0.82 and 0.44 ± 0.24, respectively. CHL_fat had nonsignificant genetic correlations with all production traits, whereas CHL_milk had significant (P < 0.05) genetic correlations with milk yield (−0.47), fat yield (0.51), protein percentage (0.56), and fat percentage (0.88). This is the first study to estimate genetic parameters for milk CHL content. Further studies are required to assess the possibility of genetically selecting cows with lower milk CHL content.
Influence of gear parameters on dynamic characteristics of an ultrasonic vibration system
Authors: Zhu De-Rong , Yang Jian-Jun , Deng Xiao-Zhong , Jiang Chuang , Li Ju-Bo
Published: April 2018

A spiral bevel gear is subject to a special load in ultrasonic lapping, which is not only a processing object but also a processing tool, it is necessary to study dynamic characteristics of an ultrasonic vibration system. First, the spiral bevel gear is reasonably simplified to a frustum, which is then combined with a horn to form a new type of composite horn. Based on the theory of plane longitudinal wave propagation, the resonance mathematical model of the gear’s ultrasonic vibration system is established, and the frequency equation of the vibration system with gear characteristic parameters is obtained. Second, the frequency and displacement characteristics of an ultrasonic vibration system are analyzed by means of design examples, and the influence of the law of gear characteristic parameters on dynamic characteristics of the vibration system is studied. Finally, ultrasonic lapping and vibration measurement experiments are carried out using two pairs of different hypoid gears. The results show that the change in dynamic characteristics of an ultrasonic vibration system has a large influence on the finished machining quality of the gear. Therefore, it is necessary to consider the gear characteristic parameters when ultrasonic vibration system is designed. The research results provide an accurate theoretical basis for the detailed design of an ultrasonic lapping vibration system.
Research on a fiber ring generating algorithm for manufacturing fiber composite rotating structures of complex geometry
Authors: Wang Xianfeng , Wang Huaqiao , Xiao Jun
Published: April 2018

Due to its light weight and high strength, carbon fiber reinforcement resin based composite (CFRC) has been widely used in aerospace, military, and many other industries. As the manufacturing technology develops, the geometry of CFRC components has seen significant changes, such as closed surface from the traditional open surface, or quite sophisticated topologies from simple shapes. As a result, fabrication of CFRC is confronted with challenging issues related to the design of fiber placement trajectory for optimal performance. In this paper, a trajectory generating algorithm is proposed based on the centroid curve of a quasi-rotational structure, where the centroid curve is the connection of centroids of the cross-sections of the structure. After the centroid curve of the component is achieved, the cross-section profiles perpendicular to the centroid curve can be determined. An efficient number of profiles are identified to avoid any overlap among neighboring profiles along the centroid curve. In this manner, the essential data for ultimate trajectory design are eventually obtained that can precisely reflect placement angles. The present work will effectively enhance the accuracy of trajectory of fiber placement and promote the mechanical property of CFRC components.
Experimental investigation on hole quality in drilling of composite pipes
Authors: Tibadia Rajkumar , Patwardhan Koustubh , Shah Dhrumil , Shinde Dinesh , Chaudhari Rakesh , Kalita Kanak
Published: April 2018

In recent years, the major reason for the rejection of composite pipes in industrial applications is due to the poor quality of the drilled hole. This paper investigates the effect of drilling process parameters on the hole quality in composite pipes made of an aluminium core surrounded by polyethylene layers. An empirical model is designed for the two input variables using response surface methodology (central composite design). An experimental investigation is carried out to study the effect of spindle speed and feed rate on quality of drilled holes, especially circularity error. It is observed that a moderate spindle speed and low feed rate are most effective in minimizing the circularity error. Microstructural investigation of drilled hole surface is also carried out using scanning electron microscopy (SEM).
Experiments on hydrolysis of Bi(2201) thin film via atomic force microscope
Authors: Li Jiapeng , Zhang Yan , Wang Haochen , Li Yusheng
Published: April 2018

In this paper, large-scale Bi(2201) nanofilm was mechanically exfoliated. The thin film Bi(2201) was characterized by means of optical image and XRD spectrum analysis. AFM is used to study the stability of Bi(2201) thin film. We found that the Bi(2201) nanofilm was less sensitive to CO2 while it extremely got affected by humidity. With the rise in the humidity, the hydrolytic speed of Bi(2201) film was greatly increased. When the relative humidity of the air is lower than 20%, the Bi(2201) thin film can be stable in two days. However, when the relative humidity is about 90% RH, Bi(2201) film will be hydrolyzed in few minutes.
Extension of lattice Boltzmann flux solver for simulation of compressible multi-component flows
Authors: Yang Li-Ming , Shu Chang , Yang Wen-Ming , Wang Yan
Published: April 2018

The lattice Boltzmann flux solver (LBFS), which was presented by Shu and his coworkers for solving compressible fluid flow problems, is extended to simulate compressible multi-component flows in this work. To solve the two-phase gas–liquid problems, the model equations with stiffened gas equation of state are adopted. In this model, two additional non-conservative equations are introduced to represent the material interfaces, apart from the classical Euler equations. We first convert the interface equations into the full conservative form by applying the mass equation. After that, we calculate the numerical fluxes of the classical Euler equations by the existing LBFS and the numerical fluxes of the interface equations by the passive scalar approach. Once all the numerical fluxes at the cell interface are obtained, the conservative variables at cell centers can be updated by marching the equations in time and the material interfaces can be identified via the distributions of the additional variables. The numerical accuracy and stability of present scheme are validated by its application to several compressible multi-component fluid flow problems.
Numerical method of carbon-based material ablation effects on aero-heating for half-sphere
Authors: Wang Jiang-Feng , Li Jia-Wei , Zhao Fa-Ming , Fan Xiao-Feng
Published: April 2018

A numerical method of aerodynamic heating with material thermal ablation effects for hypersonic half-sphere is presented. A surface material ablation model is provided to analyze the ablation effects on aero-thermal properties and structural heat conduction for thermal protection system (TPS) of hypersonic vehicles. To demonstrate its capability, applications for thermal analysis of hypersonic vehicles using carbonaceous ceramic ablators are performed and discussed. The numerical results show the high efficiency and validation of the method developed in thermal characteristics analysis of hypersonic aerodynamic heating.
A Methodology to Generate Attributed Graphs with a Bounded Graph Edit Distance for Graph-Matching Testing
Authors: Serratosa Francesc
Published: April 2018

This paper presents a methodology for generating pairs of attributed graphs with a lower and upper- bounded graph edit distance (GED). It is independent of the type of attributes on nodes and edges. The algorithm is composed of three steps: randomly generating a graph, generating another graph as a sub-graph of the first, and adding structural and semantic noise to both. These graphs, together with their bounded distances, can be used to manufacture synthetic databases of large graphs. The exact GED between large graphs cannot be obtained for runtime reasons since it has to be computed through an optimal algorithm with an exponential computational cost. Through this database, we can test the behavior of the known or new sub-optimal error-tolerant graph-matching algorithms against a lower and an upper bound GED on large graphs, even though we do not have the true distance. It is not clear how the error induced by the use of sub-optimal algorithms grows with problem size. Thus, with this methodology, we can generate graph databases and analyze if the current assumption that we can extrapolate algorithms’ behavior from matching small graphs to large graphs is correct or not. We also show that with some restrictions, the methodology returns the optimal GED in a quadratic time and that it can also be used to generate graph databases to test exact sub-graph isomorphism algorithms.
An Optimization Method for Train Seat Inventory Control
Authors: Wang Yanhui , Li Yang , Li Man , Shi Xiaowei
Published: April 2018

Railway passenger transportation plays a fundamental role in China, reasonable revenue is the guarantee of railway's regularly development such as equipment replacement, technology enhancement, etc. Although many studies on the railway revenue models have been conducted, there is a lack of effective modeling which considers the multiple trains and the multiple levels of seats in real operation. Aiming to improve the revenue of railway transportation industry, this paper proposes a new optimization method for the train seat inventory control problem with the consideration of the multiple trains and the multiple levels of seats. As the in-depth research of this problem, an integer linear programming model is formulated which aims to maximize the total revenue of rail industry. The commercial software MATLAB with CPLEX solver is employed to obtain the approximate optimal solutions. The effectiveness and performance of the proposed approaches are testified by two examples implemented on a simple railway corridor and Wuhan–Guangzhou high-speed railway corridor. Moreover, sensitivity analysis experiments are given to explore the impact on the revenue if the model parameters are changed.
ANALYTICAL SOLUTIONS FOR WATER–GAS FLOW THROUGH 3D ROCK FRACTURE NETWORKS SUBJECTED TO TRIAXIAL STRESSES
Authors: LIU RICHENG , LI BO , JING HONGWEN , WEI WEI
Published: April 2018

This study presented the analytical solutions for water–gas flow through three-dimensional (3D) fracture networks subjected to triaxial stresses. The relationship between fractal dimension for fracture aperture distribution subjected to triaxial stresses and that subjected to no stresses is established, and the analytical solutions for fractal dimensions for aperture distribution and the equivalent permeability of both fluid and gas phases were derived. The results show that the calculated relative permeability of water phase-saturation curves agree well with those reported in the literature, which indicates that the proposed solutions are validate. With the increment of normal stresses applied on the fracture surface, both the maximum aperture and minimum aperture decrease; however, their ratio increases first and then decreases. The fractal dimensions for fracture aperture distribution of water and gas phases with respect to saturation are axisymmetric along saturation [Formula: see text]. With the increase in saturation, the fractal dimension for fracture aperture distribution of water phase increases significantly when the saturation is less than 0.1, and then gently when the saturation is continuously increased by up to 1.0. The normal stress increased by two orders of magnitude for a larger normal stress (i.e. increased from [Formula: see text][Formula: see text]MPa to 10[Formula: see text]MPa) corresponds to smaller variations in equivalent permeability of both water and gas phases for a smaller normal stress (i.e. increased from [Formula: see text][Formula: see text]MPa to [Formula: see text][Formula: see text]MPa).
BOUNDS ON THE SUPPORT OF THE MULTIFRACTAL SPECTRUM OF STOCHASTIC PROCESSES
Authors: GRAHOVAC DANIJEL , LEONENKO NIKOLAI N.
Published: April 2018

The multifractal analysis of stochastic processes deals with the fine scale properties of the sample paths and seeks for some global scaling property that would enable extracting the so-called spectrum of singularities. In this paper, we establish bounds on the support of the spectrum of singularities. To do this, we prove a theorem that complements the famous Kolmogorov’s continuity criterion. The nature of these bounds helps us to identify the quantities truly responsible for the support of the spectrum. We then make several conclusions from this. First, specifying global scaling in terms of moments is incomplete due to possible infinite moments, both of positive and negative orders. The divergence of negative order moments does not affect the spectrum in general. On the other hand, infinite positive order moments make the spectrum of self-similar processes nontrivial. In particular, we show that the self-similar stationary increments process with the nontrivial spectrum must be heavy-tailed. This shows that for determining the spectrum it is crucial to capture the divergence of moments. We show that the partition function is capable of doing this and also propose a robust variant of this method for negative order moments.
EQUATIONS AND INTERVAL COMPUTATIONS FOR SOME FRACTALS
Authors: FANG LINCONG , MICHELUCCI DOMINIQUE , FOUFOU SEBTI
Published: April 2018

Very few characteristic functions, or equations, are reported so far for fractals. Such functions, called Rvachev functions in function-based modeling, are zero on the boundary, negative for inside points and positive for outside points. This paper proposes Rvachev functions for some classical fractals. These functions are convergent series, which are bounded with interval arithmetic and interval analysis in finite time. This permits to extend the Recursive Space Subdivision (RSS) method, which is classical in Computer Graphics (CG) and Interval Analysis, to fractal geometric sets. The newly proposed fractal functions can also be composed with classical Rvachev functions today routinely used in Constructive Solid Geometry (CSG) trees of CG or function-based modeling.
Succinate aggravates NAFLD progression to liver cancer on the onset of obesity: Anin silicomodel
Authors: Ray Indrani , Dasgupta Abhijit , De Rajat K.
Published: April 2018

The incidence and prevalence of nonalcoholic fatty liver disease (NAFLD) have been increasing to epidemic proportions around the world. NAFLD, a chronic liver disease that affects the nondrinkers, is mainly associated with steatohepatitis and cirrhosis. The progression of NAFLD associated with obesity increases the risk of liver cancer, a disease with poor outcomes and limited therapeutic options. In order to investigate the underlying cellular dynamics leading to NAFLD progression towards cancer on the onset of obesity, we have integrated human hepatocyte pathway with hypoxia-inducible factor1-[Formula: see text] (HIF1-[Formula: see text]) signaling pathway using state space model based on classical control theory. Modified Michaelis–Menten equation and mass action law have been used to define flux vectors of the proposed model. We have incorporated feedback inhibition/activation and allosteric effects into the simulink-based model. The values of kinetic constants have been taken from the literature. It is found that on the onset of obesity, HIF1-[Formula: see text]-induced proteins stabilize approximately 62 times that in the case of a normal cell. Consequently, the HIF1-[Formula: see text]-induced proteins enhance the enzymatic activities of hexokinase (HK), phosphofructo kinase (PFK), lactate dehydrogenase (LDH), and pyruvate dehydrogenase (PDH), which induce Warburg effect promoting an environment suitable for cancer cells.
New variable selection strategy for analysis of high-dimensional DNA methylation data
Authors: Choi Jiyun , Kim Kipoong , Sun Hokeun
Published: April 2018

In genetic association studies, regularization methods are often used due to their computational efficiency for analysis of high-dimensional genomic data. DNA methylation data generated from Infinium HumanMethylation450 BeadChip Kit have a group structure where an individual gene consists of multiple Cytosine–phosphate–Guanine (CpG) sites. Consequently, group-based regularization can precisely detect outcome-related CpG sites. Representative examples are sparse group lasso (SGL) and network-based regularization. The former is powerful when most of the CpG sites within the same gene are associated with a phenotype outcome. In contrast, the latter is preferred when only a few of the CpG sites within the same gene are related to the outcome. In this paper, we propose new variable selection strategy based on a selection probability that measures selection frequency of individual variables selected by both SGL and network-based regularization. In extensive simulation study, we demonstrated that the proposed strategy can show relatively outstanding selection performance under any situation, compared with both SGL and network-based regularization. Also, we applied the proposed strategy to identify differentially methylated CpG sites and their corresponding genes from ovarian cancer data.
Full Abstraction for Probabilistic PCF
Authors: Ehrhard Thomas , Pagani Michele , Tasson Christine
Published: April 2018

We present a probabilistic version of PCF, a well-known simply typed universal functional language. The type hierarchy is based on a single ground type of natural numbers. Even if the language is globally call-by-name, we allow a call-by-value evaluation for ground-type arguments to provide the language with a suitable algorithmic expressiveness. We describe a denotational semantics based on probabilistic coherence spaces, a model of classical Linear Logic developed in previous works. We prove an adequacy and an equational full abstraction theorem showing that equality in the model coincides with a natural notion of observational equivalence.
Non-Malleable Codes
Authors: Dziembowski Stefan , Pietrzak Krzysztof , Wichs Daniel
Published: April 2018

We introduce the notion of “non-malleable codes” which relaxes the notion of error correction and error detection. Informally, a code is non-malleable if the message contained in a modified codeword is either the original message, or a completely unrelated value. In contrast to error correction and error detection, non-malleability can be achieved for very rich classes of modifications.

We construct an efficient code that is non-malleable with respect to modifications that affect each bit of the codeword arbitrarily (i.e., leave it untouched, flip it, or set it to either 0 or 1), but independently of the value of the other bits of the codeword. Using the probabilistic method, we also show a very strong and general statement: there exists a non-malleable code for
every
“small enough” family
F
of functions via which codewords can be modified. Although this probabilistic method argument does not directly yield efficient constructions, it gives us efficient non-malleable codes in the random-oracle model for very general classes of tampering functions—e.g., functions where every bit in the tampered codeword can depend arbitrarily on any 99% of the bits in the original codeword.

As an application of non-malleable codes, we show that they provide an elegant algorithmic solution to the task of protecting functionalities implemented in hardware (e.g., signature cards) against “tampering attacks.” In such attacks, the secret state of a physical system is tampered, in the hopes that future interaction with the modified system will reveal some secret information. This problem was previously studied in the work of Gennaro et al. in 2004 under the name “algorithmic tamper proof security” (ATP). We show that non-malleable codes can be used to achieve important improvements over the prior work. In particular, we show that any functionality can be made secure against a large class of tampering attacks, simply by encoding the secret state with a non-malleable code while it is stored in memory.
Empirical Evaluation and Enhancement of Enterprise Storage System Request Scheduling
Authors: Zhou Deng , Fang Vania , Xie Tao , Pan Wen , Kesavan Ram , Lin Tony , Patel Naresh
Published: April 2018

Since little has been reported in the literature concerning enterprise storage system file-level request scheduling, we do not have enough knowledge about how various scheduling factors affect performance. Moreover, we are in lack of a good understanding on how to enhance request scheduling to adapt to the changing characteristics of workloads and hardware resources. To answer these questions, we first build a request scheduler prototype based on WAFL®, a mainstream file system running on numerous enterprise storage systems worldwide. Next, we use the prototype to quantitatively measure the impact of various scheduling configurations on performance on a NetApp®'s enterprise-class storage system. Several observations have been made. For example, we discover that in order to improve performance, the priority of write requests and non-preempted restarted requests should be boosted in some workloads. Inspired by these observations, we further propose two scheduling enhancement heuristics called SORD (size-oriented request dispatching) and QATS (queue-depth aware time slicing). Finally, we evaluate them by conducting a wide range of experiments using workloads generated by SPC-1 and SFS2014 on both HDD-based and all-flash platforms. Experimental results show that the combination of the two can noticeably reduce average request latency under some workloads.
MYD88 L265P Mutation in Lymphoid Malignancies
Authors: Yu Xinfang , Li Wei , Deng Qipan , Li Ling , Hsi Eric D. , Young Ken H. , Zhang Mingzhi , Li Yong
Published: April 2018

Next-generation sequencing has revealed cancer genomic landscapes, in which over 100 driver genes that, when altered by intragenic mutations, can promote oncogenesis. MYD88 is a driver gene found in hematologic B-cell malignancies. A missense mutation (L265P) changing leucine at position 265 to proline in MYD88 is found in ∼90% of Waldenström macroglobulinemia (WM) cases and in significant portions of activated B-cell diffuse large B-cell lymphomas and IgM monoclonal gammopathy of undetermined significance. Few cancers such as WM have a single amino acid substitution in one gene like MYD88 L265P that occurs in ∼90% of cases, making WM paradigmatic for study of a single causative mutation in oncogenesis. In this review, we summarize the frequency and cancer spectrum of MYD88 L265P and its downstream effects in lymphoid cancers. Malignant B cells with MYD88 L265P are likely transformed from IgM-producing B cells either in response to T-cell–independent antigens or in response to protein antigens before class switching. We also discuss therapeutic strategies that include targeting Bruton tyrosine kinase and other kinases, interfering with the assembly of MYD88 and its interacting partners, and MYD88 L265P-specific peptide-based immunotherapy. Cancer Res; 78(10); 2457–62. ©2018 AACR.
Association of Coffee and Tea Intake with the Oral Microbiome: Results from a Large Cross-Sectional Study
Authors: Peters Brandilyn A. , McCullough Marjorie L. , Purdue Mark P. , Freedman Neal D. , Um Caroline Y. , Gapstur Susan M. , Hayes Richard B. , Ahn Jiyoung
Published: April 2018

Background: The oral microbiota play a central role in oral health, and possibly in carcinogenesis. Research suggests that coffee and tea consumption may have beneficial health effects. We examined the associations of these common beverages with the oral ecosystem in a large cross-sectional study.

Methods: We assessed oral microbiota in mouthwash samples from 938 participants in two U.S. cohorts using 16S rRNA gene sequencing. Coffee and tea intake were assessed from food frequency questionnaires. We examined associations of coffee and tea intake with overall oral microbiota diversity and composition using linear regression and permutational MANOVA, respectively, and with taxon abundance using negative binomial generalized linear models; all models adjusted for age, sex, cohort, body mass index, smoking, ethanol intake, and energy intake.

Results: Higher tea intake was associated with greater oral microbiota richness (P = 0.05) and diversity (P = 0.006), and shifts in overall community composition (P = 0.002); coffee was not associated with these microbiome parameters. Tea intake was associated with altered abundance of several oral taxa; these included Fusobacteriales, Clostridiales, and Shuttleworthia satelles (higher with increasing tea) and Bifidobacteriaceae, Bergeyella, Lactobacillales, and Kingella oralis (lower with increasing tea). Higher coffee intake was only associated with greater abundance of Granulicatella and Synergistetes.

Conclusions: In the largest study to date of tea and coffee consumption in relation to the oral microbiota, the microbiota of tea drinkers differed in several ways from nondrinkers.

Impact: Tea-driven changes to the oral microbiome may contribute to previously observed associations between tea and oral and systemic diseases, including cancers. Cancer Epidemiol Biomarkers Prev; 27(7); 814–21. ©2018 AACR.
Actionable Locoregional Relapses after Therapy of Localized Esophageal Cancer: Insights from a Large Cohort
Authors: Elimova Elena , Wang Xuemei , Qiao Wei , Sudo Kazuki , Wadhwa Roopma , Shiozaki Hironori , Shimodaira Yusuke , Planjery Venkatram , Charalampakis Nikolaos , Lee Jeffrey H. , Weston Brian R. , Bhutani Manoop S. , Komaki Ritsuko , Rice David C. , Swisher Stephen G. , Blum Mariela A. , Rogers Jane E. , Skinner Heath D. , Maru Dipen M. , Hofstetter Wayne L. , Ajani Jaffer A.
Published: April 2018

Objective: The goal of surveillance after therapy of localized esophageal cancer (LEC) is to identify actionable relapses amenable to salvage; however, the current surveillance algorithms are not optimized. We report on a large cohort of LEC patients with actionable locoregional relapses (LRRs). Methods: Between 2000 and 2013, 127 (denominator = 752) patients with actionable LRR were identified. Histologic/cytologic confirmation was the gold standard. All surveillance tools (imaging, endoscopy, fine needle aspiration) were assessed. Results: Most patients were men (89%), had adenocarcinoma (79%), and had no new symptoms (72%) when diagnosed with LRR. In trimodality patients, endoscopic confirmation of positron emission tomography-computed tomography-suspected LRR occurred in only 44%, and 56% required additional tools (e.g., fine needle aspiration). Alternatively, in bimodality patients, endoscopy confirmed LRRs in 81%. Trimodality patients had a higher risk of subsequent LRR/distant metastases after the first LRR than the bimodality patients (p = 0.03). In all patients, 78% of the subsequent relapses were distant. For patients who were salvaged, survival was significantly prolonged (50.6 vs. 25.1 months, p < 0.01). Conclusions: Patients live longer after successful salvage of the LRR than if salvage is not possible. After LRR, patients have a high risk of subsequent distant metastasis and whether the second relapse is local or distant, survival is uniformly poor.
Indacaterol/Glycopyrronium in the Treatment of Severe Respiratory Failure: Marked Improvement of Respiratory Failure in a Few Weeks – A Case Report
Authors: Pistelli Riccardo , Castriotti Maria Rosaria , Panico Loredana
Published: April 2018

Chronic obstructive pulmonary disease is a highly prevalent disease, especially in the aging population, associated with several functional disabilities and a high economic burden. Dual bronchodilation with prefixed associations of long-acting β2-agonists and long-acting muscarinic antagonist have a significant role in the management of this condition. The newer combination, indacaterol/glycopyrronium, is useful as a once-a-day therapy and has proven superior to other treatment strategies including inhaled corticosteroids for improving symptoms and clinical condition with a very rapid effect. We report our experience with a patient suffering from severe respiratory failure who improved significantly when the indacaterol/glycopyrronium combination was added to his therapy.
Combination Therapy of Inhaled Indacaterol/Glycopyrronium for Chronic Obstructive Pulmonary Disease in the Very Elderly: Is It Safe? An Electrocardiographic Evaluation
Authors: Spannella Francesco , Giulietti Federico , Cesari Valentina , Francioso Antonio , Cocci Guido , Landi Laura , Lombardi Francesca Elena , Borioni Elisabetta , Bernardi Beatrice , Rosettani Giulia , Bordoni Valentina , Iacoacci Corrado , Giordano Piero , Sarzani Riccardo
Published: April 2018

Cardiovascular (CV) comorbidities in patients with chronic obstructive pulmonary disease (COPD) are associated with increased morbidity and mortality, especially in old and very old subjects. The question if long-acting beta-agonist and long-acting muscarinic antagonist could be associated with the increased prevalence of CV-related adverse effects has puzzled, particularly in the past, specialists involved in the management of respiratory diseases. The safety of these compounds has scarcely been tested in patients aged ≥ 65 years with CV comorbidities, since randomized controlled trials rarely include this subpopulation. However, the fixed combination indacaterol/glycopyrronium has shown a favorable CV safety profile in both healthy volunteers and COPD patients. Thus, we aimed to assess the CV safety pro­- file of the fixed combination indacaterol/glycopyrronium 110/50 μg in a series of COPD patients aged ≥ 80 years with several comorbidities. Our results indicate that this combination is safe in the comorbid elderly, since no significant electrocardiographic abnormalities were recorded after the administration of the inhaled therapy. Only rare and nonclinically significant changes in heart rate and corrected QT interval duration were evident, mainly in females and in patients with concomitant impaired kidney function.
Multifocal Primary Uveal Melanoma: Clinical and Molecular Characteristics
Authors: Echegaray Jose J. , Medina Carlos A. , Biscotti Charles V. , Plesec Thomas , Singh Arun D.
Published: April 2018

We report two patients who developed a second distinct choroidal melanoma in the same eye following successful regression of their first choroidal melanoma after iodine-125 plaque brachytherapy. Neither patient demonstrated ocular melanocytosis, local tumor recurrence, or vitreous seeding. One patient had the second tumor arising from a previously documented choroidal nevus, and after undergoing enucleation, there was no detectable connection between the tumors on histopathologic examination. Germline BAP1 mutation was absent in both cases. Multifocal primary uveal melanoma is a rare entity in which the second tumor may occur either de novo or from a malignant transformation of a choroidal nevus. Known risk factors include ocular melanocytosis or germline BAP1 mutation. Additional underlying mechanisms have yet to be elucidated.
Influence of the Histopathological Features of the Lesion on the Diagnostic Yield of Fine-Needle Aspiration Cytology of Pancreatic Solid Lesions
Authors: Fernández Aceñero M. Jesús , Vázquez M. , Esteban J.M. , García Diego Guillermo , Díaz del Arco Cristina
Published: April 2018

Objective: The rate of pancreatic lesions has increased in recent decades due to the widespread use of advanced imaging techniques. Nowadays, a significant proportion of cases are incidentally discovered in asymptomatic patients and cytology is an important tool for the diagnosis and multidisciplinary management of these cases. Study Design: In this study we retrospectively review the experience with pancreatic fine-needle aspiration cytology in the last 17 years at a single large tertiary hospital in Madrid, Spain. Results: Our results indicate that more than 60% of pancreatic malignant lesions are cytologically confirmed before surgery and 30% of the patients are asymptomatic. Despite this, we have noted that the total number of malignant lesions surgically resected in our hospital has basically remained unchanged over the years, because incidental diagnosis is not always synonymous with resectability and a substantial number of patients are already metastatic at the time of diagnosis. Our series also shows an increase in the number of neuroendocrine tumors, which now represent almost 20% of all cytological diagnoses at our hospital. The sensitivity in our series is 70% and the false negative rate remains 30%, despite sample quality control by experienced cytologists and standardized technical conditions. Fibrosis and necrosis are the 2 features of the primary tumor that significantly and negatively influence the accuracy of cytologic diagnosis. Conclusion: We herein report our experience with cytologic diagnosis of pancreatic lesions in a single tertiary hospital. Our results confirm that cytology is a safe, reliable, and important tool for pancreatic lesion diagnosis and management.
The Effect of Age and Body Mass Index on the Surgical Anatomy of Supraumbilical Port Insertion: Implications for Laparoscopic and Robotic Surgery
Authors: Bedaiwy Mohamed A. , Yong Paul J. , Farghaly Tarek A. , Abdelhafez Faten F. , Tan Justin , Pope Rachel , Hurd William W. , Liu James H. , Zanotti Kristine
Published: April 2018

Background: Minimally invasive surgery is the preferred approach for performing many gynecologic procedures. Occasionally, supraumbilical port placement may be preferable to optimize visibility and maneuverability although the risks of complications are less well characterized compared to umbilical entry. Methods: We conducted a retrospective review of computed tomograms from 92 patients to evaluate the anatomic considerations for umbilical and supraumbilical port entry based on patient age, body mass index (BMI), parity, abdominal wall thickness, and distance to the great vessels. Results: Supraumbilical entry was not associated with differences in distance to the great vessels compared to the umbilicus. However, supraumbilical location and BMI were associated with greater abdominal wall thickness. Age and BMI were associated with greater distance to the great vessels, while age was associated with thinner abdominal wall. Multiple linear regression confirmed independent effects of age and BMI. No association between parity and distance to retroperitoneal vessels was observed. Conclusion: Younger patients may be at increased risk for great vessel injury and pre-peritoneal insufflation. Obese patients may be at risk for pre-peritoneal insufflation, while patients with BMI < 30, particularly with a skin-to-aorta distance < 7 cm, may be at an increased risk for great vessel injury. Surgeons should consider these factors when considering supraumbilical port entry.
Immunotherapy of Hepatocellular Carcinoma
Authors: Heinrich Bernd , Czauderna Carolin , Marquardt Jens U.
Published: April 2018

Hepatocellular carcinoma (HCC) is one of the most deadly and rapidly evolving cancers worldwide. The current systemic treatment strategies in advanced tumor stages remain limited despite promising preclinical and early-phase clinical results for some compounds, highlighting an unmet clinical need. Since the majority of HCCs evolve in the background of a chronic inflammatory liver damage, HCCs can be considered a paradigm for inflammation-induced cancers, which renders immunotherapeutic strategies particularly promising for this tumor entity. Consequently, an improved understanding of key oncogenic and immune response signaling pathways as well as increasing appreciation of the diseased microenvironment for HCC initiation and progression has led to the development of a diverse range of immune-oncological interventions during the last decade. Besides oncolytic viruses, vaccines, or immune cell infusions, first results from early-phase clinical trials particularly encourage the use of immune checkpoint inhibitors against PD-1/PD-L1 and CTLA-4 for HCC. In this review, we delineate the current clinical and preclinical landscape of immunotherapies in HCC, critically discuss recent findings from clinical trials and outline future perspectives in the field of liver cancer.
Immunotherapy and Combination Strategies in Pancreatic Cancer: Current Status and Emerging Trends
Authors: Cheung Phyllis F. , Lutz Manfred , Siveke Jens T.
Published: April 2018

Pancreatic cancer is among the most aggressive malignancies with no effective therapeutic options thus far. Immunotherapy has recently emerged as a promising alternative for the treatment of various solid tumors. In particular, promising results in clinical trials were observed for therapies targeting immune checkpoint molecules. Efforts have been put into investigating the potential of immunotherapy in treating pancreatic cancer. While most of the clinical trial results are still being awaited, several intrinsic features of pancreatic cancer such as low mutational load and the presence of highly immunosuppressive desmoplasia significantly hamper the efficacy of immunotherapy in this disease. These unique features of pancreatic cancer, however, have advanced our understanding of tumor immunology and might help to tailor the future direction of immunotherapy. In this review, we summarize the current immunotherapeutic strategies and clinical trials targeting checkpoint molecules in pancreatic cancer. Emerging trends towards various combinations with therapies targeting immunosuppressive myeloid cells are also discussed.
Multidetector-Row Computed Tomography and Colonoscopy for Detecting a Rectal Dieulafoy Lesion as a Source of Lower Gastrointestinal Hemorrhage
Authors: Kaneko Manabu , Nozawa Hiroaki , Tsuji Yosuke , Emoto Shigenobu , Murono Koji , Nishikawa Takeshi , Sasaki Kazuhito , Otani Kensuke , Tanaka Toshiaki , Hata Keisuke , Kawai Kazushige , Koike Kazuhiko
Published: April 2018

A Dieulafoy lesion of the rectum is a very rare entity that can cause massive lower gastrointestinal (GI) hemorrhage. Identifying the bleeding point is sometimes difficult because these lesions are very small. We herein describe an 82-year-old man with active hemorrhage due to a rectal Dieulafoy lesion. He was referred to our hospital because of persistent hematochezia from the morning of that day. He had a history of atrial fibrillation, chronic heart failure, diabetes mellitus, and hyperuricemia. Prompt multidetector-row computed tomography (MDCT) enabled us to detect active bleeding from the lower rectum. Subsequently, colonoscopy revealed an exposed vessel in the lower rectum without surrounding ulceration, and hemostasis was successfully achieved using a hemostatic forceps with soft coagulation. After hemostasis had been achieved, the patient recovered and was discharged without complications and rebleeding. He is doing well 6 months after discharge from the hospital. Sequential examination by MDCT and colonoscopy is considered an efficient treatment strategy for patients with active lower GI bleeding.
Immune Checkpoint Inhibition in Gastro-Oesophageal Cancer
Authors: Smyth Elizabeth , Thuss-Patience Peter C.
Published: April 2018

Recently some progress has been made in the palliative treatment of gastric cancer. It was shown that second-line chemotherapy and VEGF-R2-directed treatment can prolong survival. Despite these advances most patients with metastatic gastric cancer live for less than 2 years. Immune-checkpoint blockade with anti-CTLA4, anti-PD-1 and anti-PD-L1 antibodies has revolutionised the treatment of many cancers. Significant benefit was also proven in gastric adenocarcinomas. Nivolumab improves overall survival as third-line treatment in Asian gastric cancer patients and is already registered in Japan. Pembrolizumab shows significant efficacy, especially in PD-L1-positive patients as third-line treatment and is FDA approved for this indication. Trials with avelumab are promising and studies with atezolizumab and durvalumab are also on the way. To extend the subgroup of benefitting patients combinations of PD-1/PD-L1 antibodies with CTLA4, or VEGF-R2 antibodies or combination with chemotherapy are investigated and show promising results. In this article, the existing evidence of PD1 and PD-L1 blockade as monotherapy or in combination with anti-CTLA4, anti-VEGF-R2 and chemotherapy in gastro-oesophageal adenocarcinoma is reviewed and put into perspective.
Genome-Wide Association Study and Transcriptome Analysis Provide New Insights into the White/Red Earlobe Color Formation in Chicken
Authors: Luo Wei , Xu Jiguo , Li Zhenhui , Xu Haiping , Lin Shudai , Wang Jiaying , Ouyang Hongjia , Nie Qinghua , Zhang Xiquan
Published: April 2018

Background/Aims: Earlobe color is a typical external trait in chicken. There are some previous studies showing that the chicken white/red earlobe color is a polygenic and sex-linked trait in some breeds, but its molecular genetic and histological mechanisms still remain unclear. Methods: We herein utilized histological section, genome-wide association study (GWAS) and RNA-seq, further to investigate the potential histological and molecular genetic mechanisms of white/red earlobe formation in Qiangyuan Partridge chicken (QYP). Results: through histological section analysis, we found the dermal papillary layer of red earlobes had many more blood vessels than that of white earlobes. And we identified a total of 44 SNPs from Chromosome 1, 2, 3, 4, 9, 10, 11, 13, 19, 20, 23 and Z, that was significantly associated with the chicken white/red earlobe color from GWAS, along with 73 significantly associated genes obtained (e.g., PIK3CB, B4GALT1 and TP63), supporting the fact that the white/red earlobe color was also polygenic and sex-linked in QYP. Importantly, PIK3CB and B4GALT1 are both involved in the biological process of angiogenesis, which may directly give rise to the chicken white earlobe formation through regulating blood vessel density in chicken earlobe. Additionally, through contrast of RNA-seq profiles between white earlobe skins and red earlobe skins, we further identified TP63 and CDH1 differentially expressed. Combined with the existing knowledge of TP63 in epithelial development and tumor angiogenesis, we propose that down-regulated TP63 in white earlobes may play roles in thickening the skin and decreasing the vessel numbers in dermal papillary layer, thereby contributing to the white earlobe formation via paling the redness of the skin in QYP, but the specific mechanism remains to be further clarified. Conclusion: our findings advance the existing understanding of the white earlobe formation, as well as provide new clues to understand the molecular mechanism of chicken white/red earlobe color formation.
Salidroside Protection Against Oxidative Stress Injury Through the Wnt/β-Catenin Signaling Pathway in Rats with Parkinson’s Disease
Authors: Wu Dong-Mei , Han Xin-Rui , Wen Xin , Wang Shan , Fan Shao-Hua , Zhuang Juan , Wang Yong-Jian , Zhang Zi-Feng , Li Meng-Qiu , Hu Bin , Shan Qun , Sun Chun-Hui , Lu Jun , Zheng Yuan-Lin
Published: April 2018

Background/Aims: Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease, and recent studies suggested that oxidative stress (OS) contributes to the cascade that leads to dopamine cell degeneration in PD. In this study, we hypothesized that salidroside (SDS) offers protection against OS injury in 6-hydroxydopamine (6-OHDA) unilaterally lesioned rats as well as the underlying mechanism. Methods: SDS and LiCl (activators of the Wnt/β-catenin signaling pathway) administration alone and in combination with 6-OHDA injection in rats was performed 3 days before modeling for 17 consecutive days to verify the regulatory mechanism by which SDS affects the Wnt/β-catenin signaling pathway as well as to evaluate the protective effect of SDS on PD in relation to OS in vivo. In addition, pheochromocytoma 12 (PC12) cells were incubated with 10 µmol/L SDS or LiCl alone or with both in combination for 1 h followed by a 24-h incubation with 100 µmol/L 6-OHDA to obtain in vitro data. Results: In vivo the administration of LiCl was found to ameliorate behavioral deficits and dopaminergic neuron loss; increase superoxide dismutase (SOA) activity, glutathione peroxidase (GSH-Px) levels, and glycogen synthase kinase 3β phosphorylation (GSK-3β-Ser9); reduce malondialdehyde (MDA) accumulation in the striatum and the GSK-3β mRNA level; as well as elevate β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-injected rats. This SDS treatment regimen was found to strengthen the beneficial effect of LiCl on 6-OHDA-injected rats. In vitro LiCl treatment decreased the toxicity of 6-OHDA on PC12 cells and prevented apoptosis. Additionally, LiCl treatment increased SOA activity, GSH-Px levels, and GSK-3β-Ser9 phosphorylation; decreased MDA accumulation in the striatum and GSK-3β mRNA levels; as well as increased β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-treated PC12 cells. Additionally, SDS treatment increased the protective effect of LiCl on 6-OHDA-treated PC12 cells. Conclusion: Evidence from experimental models suggested that SDS may confer neuroprotection against the neurotoxicity of 6-OHDA in response to OS injury and showed that these beneficial effects may be related to regulation of the Wnt/β-catenin signaling pathway. Therefore, SDS might be a potential therapeutic agent for treating PD.