bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomised clinical trial showing the curative effect of bandaging on M2‐stage lesions of digital dermatitis in dairy cows
Authors: Klawitter Marcus , Döpfer Dörte , Braden Theo Broderick , Amene Ermias , Mueller Kerstin Elisabeth
Published: May 2019

Objectives and design

This trial evaluated the effect of bandaging of acute painful ulcerative bovine digital dermatitis (DD) lesion (stage M2) in dairy cows, tested using two different topical treatments.

Design

Randomised clinical trial.

Setting

This study was conducted using Holstein‐Friesian cows ranging in age from heifers to fourth lactation in a single dairy herd and diagnosed with acute ulcerative DD lesions (stage M2) on the first examination (week 0). Cows were randomly assigned into either a non‐bandaged or bandaged group across two treatment conditions: topical chlortetracycline spray (CTC) and Intra Hoof‐Fit Gel (IHF). Lesions received standardised bandaging and treatment on a weekly basis. Unhealed lesions could receive up to five repeated treatments, at weekly intervals, within a four‐week period. Both M‐stage and locomotion were also evaluated and scored weekly. Cows with healthily formed skin (stage M0) were deemed healed and subsequently released from the study.

Results

In total, 163 M2 lesions were diagnosed at week 0. Bandaged M2 lesions had a significantly higher probability of cure than non‐bandaged lesions regardless of treatment type (HR: 4.1; P<0.001; 95 per cent CI: 2.5 to 6.8). Most healing occurred within the first three weeks of trial. Furthermore, bandaged lesions (group 2 and group 4) were significantly less likely to progress into the chronic hyperkeratotic or proliferative stage (M4) than non‐bandaged lesions in group 1 and group 3 (HR: 0.10; P<0.001; 95 per cent CI: 0.04 to 0.22). Out of concern for the cow's wellbeing, this study investigated the effects of bandaging on locomotion. Bandaging had no effect on locomotion for either cows treated with CTC (group 1: median Sprecher score, 2; IQR=1–2; group 2: median Sprecher score, 2; IQR=1–3; P=0.3) or IHF (group 3: median Sprecher score, 2; IQR=1–2; group 4: median Sprecher score, 2; IQR=1–3; P=0.3).
Reflections on the energy of black holes
Authors: Dray Tevian , Rovelli Carlo
Published: May 2019

Inside a black hole, there is no local way to say which side of a sphere is the inside, and which is the outside. One can easily be gulled by this fact into mixing up the sign of the energy. We lead the reader astray with a naïve treatment of the energy of a null shell in black hole spacetimes. We then resolve the confusion, showing that global, rather than local, considerations offer good guidance.
Catalytic toluene combustion over Pt loaded on lanthanum silicate with apatite-type structure
Authors: Matsuo Kenji , Nunotani Naoyoshi , Imanaka Nobuhito
Published: May 2019

Novel Pt/La[Formula: see text]Si5CoO[Formula: see text]-Al2O3 catalysts were developed for complete toluene combustion, and their catalytic activities were investigated. The introduction of the La[Formula: see text]Si5CoO[Formula: see text] promoter enhanced the reducibility and the catalytic activity due to its oxygen release ability. Among the samples prepared in this study, the 10[Formula: see text]wt.% Pt/10[Formula: see text]wt.% La[Formula: see text]Si5CoO[Formula: see text]-Al2O3 catalyst showed the highest catalytic activity, allowing the complete toluene combustion at 120∘C. In addition, the catalyst possesses high water durability.
Large Large-Trader Activity Weakens the Long Memory of Limit Order Markets
Authors: Primicerio Kevin , Challet Damien
Published: May 2019

Using more than 6.7 billions of trades, we explore how the tick-by-tick dynamics of limit order books is influenced by the aggregate quarterly actions of large investment funds. In particular, we find that the well-established long memory of market order signs is markedly weaker when large investment funds trade in a directional way and even weaker when their aggregate participation ratio is large. Conversely, we investigate to what extent a weaker memory of market order signs predicts that an asset is being actively traded by large funds. Theoretical arguments suggest two candidate mechanisms that may contribute to the observed effect: a larger number of active meta-orders and a modification of the distribution of size of meta-orders. Empirical evidence suggests that the number of active meta-orders is probably the most important contributor to the reduction of market order sign memory.
On the Complexity of Non-Segregated Routing in Reconfigurable Data Center Architectures
Authors: Foerster Klaus-Tycho , Pacut Maciej , Schmid Stefan
Published: May 2019

By enhancing the traditional static network (e.g., based on electric switches) with a dynamic topology (e.g., based on reconfigurable optical switches), emerging reconfigurable data centers introduce unprecedented flexibilities in how networks can be optimized toward the workload they serve. However, such hybrid data centers are currently limited by a restrictive routing policy enforcing artificial segregation: each network flow can only use either the static or the flexible topology, but not a combination of the two.

This paper explores the algorithmic problem of supporting more general routing policies, which are not limited by segregation. While the potential benefits of non-segregated routing have been demonstrated in recent work, the underlying algorithmic complexity is not well-understood.

We present a range of novel results on the algorithmic complexity of non-segregated routing. In particular, we show that in certain specific scenarios, optimal data center topologies with nonsegregated routing policies can be computed in polynomial-time. In many variants of the problem, however, introducing a more flexible routing comes at a price of complexity: we prove several important variants to be NP-hard.
Evaluating the artifacts of SIGCOMM papers
Authors: Saucez Damien , Iannone Luigi , Bonaventure Olivier
Published: May 2019

A growing fraction of the papers published by CCR and at SIGCOMM-sponsored conferences include artifacts such as software or datasets. Besides CCR, these artifacts were rarely evaluated. During the last months of 2018, we organised two different Artifacts Evaluation Committees to which authors could submit the artifacts of their papers for evaluation. The first one evaluated the papers accepted by Conext’18 shortly after the TPC decision. It assigned ACM reproducibility badges to 12 different papers. The second one evaluated papers accepted by CCR and any SIGCOMM-sponsored conference. 28 papers received ACM reproducibility badges. We report on the results of a short survey among artifacts authors and reviewers and provide some suggestions for future artifacts evaluations.
Resistance-exercise training ameliorates LPS-induced cognitive impairment concurrent with molecular signaling changes in the rat dentate gyrus
Authors: Kelty Taylor J. , Schachtman Todd R. , Mao Xuansong , Grigsby Kolter B. , Childs Thomas E. , Olver T. Dylan , Michener Paige N. , Richardson Rachel A. , Roberts Christian K. , Booth Frank W.
Published: May 2019

Effective treatments preventing brain neuroinflammatory diseases are lacking. Resistance-exercise training (RT) ameliorates mild cognitive impairment (MCI), a forerunner to neuroinflammatory diseases. However, few studies have addressed the molecular basis by which RT abates MCI. Thus experiments were performed to identify some molecular changes occurring in response to RT in young, female Wistar rats. To induce MCI, intraventricular lipopolysaccharide (LPS) injections were used to increase dentate gyrus inflammation, reflected by significantly increased TNF-α (~400%) and IL-1β (~1,500%) mRNA ( P < 0.0001) after 6 wk. Five days after LPS injections, half of LPS-injected rats performed RT by ladder climbing for 6 wk, 3 days/wk, whereas half remained without ladders. RT for 6 wk increased lean body mass percentage ( P < 0.05), individual muscle masses (gastrocnemius and tibialis anterior) ( P < 0.05), and maximum lifting capacity ( P < 0.001). The RT group, compared with sedentary controls, had 1) ameliorated spatial learning deficits ( P < 0.05), 2) increased dentate gyrus phosphorylation of IGF-1R, protein kinase B, and GSK-3β proteins ( P < 0.05), components of downstream IGF-1 signaling, and 3) increased dentate gyrus synaptic plasticity marker synapsin protein ( P < 0.05). Two follow-up experiments (without LPS) characterized dentate gyrus signaling during short-term RT. Twenty-four hours following the third workout in a 1-wk training duration, phosphorylation of ERK1/2 and GSK-3β proteins, as well as proliferation marker protein, PCNA, were significantly increased ( P < 0.05). Similar changes did not occur in a separate group of rats following a single RT workout. Taken together, these data indicate that RT ameliorates LPS-induced MCI after RT, possibly mediated by increased IGF-1 signaling pathway components within the dentate gyrus.

NEW & NOTEWORTHY The data suggest that resistance-exercise training restores cognitive deficits induced by lipopolysaccharides and can activate associated IGF-1 signaling in the dentate gyrus. Our data show, for the first time, that as few as three resistance-exercise workouts (spread over 1 wk) can activate IGF-1 downstream signaling and increase proliferation marker PCNA in the dentate gyrus.
A Lightweight Fine-Grained Searchable Encryption Scheme in Fog-Based Healthcare IoT Networks
Authors: Li Hui , Jing Tao
Published: May 2019

For a smart healthcare system, a cloud based paradigm with numerous user terminals is to support and improve more reliable, convenient, and intelligent services. Considering the resource limitation of terminals and communication overhead in cloud paradigm, we propose a hybrid IoT-Fog-Cloud framework. In this framework, we deploy a geo-distributed fog layer at the edge of networks. The fogs can provide the local storage, sufficient processing power, and appropriate network functions. For the fog-based healthcare system, data confidentiality, access control, and secure searching over ciphertext are the key issues in sensitive data. Furthermore, how to adjust the storage and computing requirements to meet the limited resource is also a great challenge for data management. To address these, we design a lightweight keyword searchable encryption scheme with fine-grained access control for our proposed healthcare related IoT-Fog-Cloud framework. Through our design, the users can achieve a fast and efficient service by delegating a majority part of the workloads and storage requirements to fogs and the cloud without extra privacy leakage. We prove our scheme satisfies the security requirements and demonstrate the excellent efficiency through experimental evaluation.
Experimental Study on Directional Fracture Blasting of Cutting Seam Cartridge
Authors: Yang Renshu , Zuo Jinjing
Published: May 2019

Since the cutting seam cartridge has sound directional breaking effect, in order to explore its blasting wave mechanism, an experimental study was conducted on the blast wave of a cutting seam cartridge using a high‐speed laser schlieren system and air overpressure test system. The research results show that during cartridge explosion, the cutting seam pipe can effectively control the energy release and detonation gas dynamic behaviors. Additionally, the cartridge blast wave and the detonation gas remain highly symmetrical in expansion form. The blast wave first propagates along the cutting seam direction, and the detonation gas initially expands from the seam in the direction of the cutting seam. The pressure in the cutting seam direction is higher than that in the noncutting seam direction. The blast wave change of the whole flow field of the cutting seam cartridge was numerically simulated and was basically consistent with the results of the schlieren test in distribution form. The presence of a cutting seam prolongs the blast wave effect. During expansion of the cutting seam pipe under the influence of a blast wave, the inner wall of the cutting seam pipe is mainly subject to tensile stress. When the tensile force applied to the inner wall reaches the local yield limit, the cutting seam pipe fails.
Efficient Attribute-Based Encryption with Privacy-Preserving Key Generation and Its Application in Industrial Cloud
Authors: Song Yujiao , Wang Hao , Wei Xiaochao , Wu Lei
Published: May 2019

Due to the rapid development of new technologies such as cloud computing, Internet of Things (IoT), and mobile Internet, the data volumes are exploding. Particularly, in the industrial field, a large amount of data is generated every day. How to manage and use industrial Big Data primely is a thorny challenge for every industrial enterprise manager. As an emerging form of service, cloud computing technology provides a good solution. It receives more and more attention and support due to its flexible configuration, on-demand purchase, and easy maintenance. Using cloud technology, enterprises get rid of the heavy data management work and concentrate on their main business. Although cloud technology has many advantages, there are still many problems in terms of security and privacy. To protect the confidentiality of the data, the mainstream solution is encrypting data before uploading. In order to achieve flexible access control to encrypted data, attribute-based encryption (ABE) is an outstanding candidate. At present, more and more applications are using ABE to ensure data security. However, the privacy protection issues during the key generation phase are not considered in the current ABE systems. That is to say, the key generation center (KGC) knows both of attributes and corresponding keys of each user. This problem is especially serious in the industrial big data scenario, because it will cause great damage to the business secrets of industrial enterprises. In this paper, we design a new ABE scheme that protects user’s privacy during key issuing. In our new scheme, we separate the functionality of attribute auditing and key generating to ensure that the KGC cannot know user’s attributes and that the attribute auditing center (AAC) cannot obtain the user’s secret key. This is ideal for many privacy-sensitive scenarios, such as industrial big data scenario.
BIM‐Based Digital Fabrication Process for a Free‐Form Building Project in South Korea
Authors: Lee Joo-sung , Kwon Nahyun , Ham Nam-hyuk , Kim Jae-jun , Ahn Yong-han
Published: May 2019

Since the concept of building information modeling (BIM) was introduced in South Korea in 2008, digital fabrication concerning free‐form shapes and complex parametric information has been expanding owing to the development of BIM software and tools. However, the digital fabrication process is inadequate in terms of efficiency and productivity because of the need to convert from conventional two‐dimensional (2D) drawings to a BIM design; this adversely affects the unified design, fabrication, installation, and inspection processes. Moreover, an optimized process has not been developed thus far because the productivity of digital fabrication has not been quantitatively verified for various projects in the field. This study proposes a BIM‐based digital fabrication process for prefabricated parts of buildings. In addition, a productivity analysis method based on the queuing model is proposed using personnel input and performance calculation data to verify productivity. It is expected that the digital fabrication process and productivity analysis model proposed here will be applied to complex digital fabrication works.
A Practical Authentication Framework for VANETs
Authors: Wang Baosheng , Wang Yi , Chen Rongmao
Published: May 2019

In vehicular ad hoc networks (VANETs), conditional privacy preserving authentication (CPPA) scheme is widely deployed to solve security and privacy issues. Existing CPPA schemes usually require ideal tamper-proof devices (TPDs) on vehicles which, however, might be infeasible or do not exist in reality due to high security requirements. To address this problem, we propose a practical framework of CPPA scheme that supports more realistic TPDs which are less secure correspondingly. We demonstrate that this framework also manages to achieve nonframeability in addition to other security objectives including nonrepudiation, conditional privacy preserving, and unlinkability. Moreover, performance analysis shows that our framework has better efficiency in authentication. All these features make our framework practical for VANETs.
LC-MS/MS Analysis and Hepatoprotective Activity of Artichoke (Cynara scolymusL.) Leaves Extract against High Fat Diet-Induced Obesity in Rats
Authors: Ben Salem Maryem , Ksouda Kamilia , Dhouibi Raouia , Charfi Slim , Turki Mouna , Hammami Serria , Ayedi Fatma , Sahnoun Zouheir , Zeghal Khaled Mounir , Affes Hanen
Published: May 2019

Cynara scolymusL. (Artichoke) has been used for the treatment of metabolic disorders. The purpose of the present study was to investigate the hepatoprotective effect ofCynara scolymusleaves extract against a high fat diet (HFD) induced rats. This study investigated the most abundant phenolic compounds richCynara scolymusleaves extract and it is antihypercholesterolemic and antioxidative effectsin vivo. The hypercaloric high fat diet (HFD) was treated with 200 mg/kg and 400 mg/kg of ethanol extract (EEA) from leaves ofCynaraand atorvastatin (ATOR) (10 mg/kg/day) during an 8-week period. Lipid profile was measured and oxidative stress systematic in hepatic tissue was determined. Our data revealed that HFD-induced hepatic dysfunction manifested by significant abnormal levels of AST, ALT, ALP, LDH, and OCT was accompanied by increasing levels of oxidative stress biomarker (ROS, MDA, and AOPP) while decreasing in antioxidant status. Coadministration of EEA significantly reduced serum lipid profile and hepatic disorders which was confirmed to be histological by reducing the fatty liver deposition in hepatic lobule. These findings suggest thatCynaraleaves exert antiobesity and antioxidant liver effects in HFD-induced obese rats.
Effects of Fine-Grained Particles’ Migration and Clogging in Porous Media on Gas Production from Hydrate-Bearing Sediments
Authors: Jung Jongwon , Kang Hongsig , Cao Shuang Cindy , Al-Raoush Riyadh I. , Alshibli Khalid , Lee Joo Yong
Published: May 2019

The migration of fine particles in porous media has been studied for different applications, including gas production from hydrate-bearing sediments. The clogging behavior of fine particles is affected by fine particle-pore throat size ratio, fine particle concentration, ionic concentration of fluids, and single/multiphase fluid flow. While previous studies presented valuable results, the data are not enough to cover a broad range of particle types and sizes and pore throat size in natural hydrate-bearing sediments. This paper presents a novel micromodel to investigate the effects of fine particle-pore throat size ratio, fine concentration, ionic concentration of fluid, and single/multiphase fluid flow on clogging or bridging in porous media. The results show that (1) the concentration of fine particles required to form clogging and/or bridging in pores decreased with the decrease in fine particle-pore throat size ratio, (2) the effects of ionic concentration of fluid on clogging behaviors depend on the types of fine particles, and (3) fine particles prefer to accumulate along the deionized water- (DW-) CO2 interface and migrate together, which in turn easily causes clogging in pores. As a result, multiphase fluid flow during gas production from hydrate-bearing sediments could easily develop clogging in pore throats, where the relative permeability of DW-CO2 in porous media decreases. Accordingly, the relatively permeability of porous media should be evaluated by considering the clogging behavior of fines.
A Case of Acute Myocardial Infarction in a Patient Whose Initial Complaints Were Hematemesis and Epigastric Discomfort
Authors: Omori Kazuhiko , Yanagawa Youichi
Published: May 2019

The patient was a 64-year-old woman with systemic lupus erythematosus, thrombophlebitis of the lower legs, cerebral infarction with left hemiparesis, and colostomy after perforation of the sigmoid colon. On the morning of her presentation, the patient felt epigastric abnormality. Thereafter, hematemesis occurred twice, leading her to call an ambulance in the afternoon. Upon arrival, electrocardiography before securing a venous route and obtaining blood samples revealed ST segment elevation in leads II, III, and aVF. As her vital signs were stable and her hemoglobin level had decreased by just 1.1 g/dl in comparison to the previous day, emergency coronary angiography (CAG) was performed. CAG revealed complete occlusion at section #4. She underwent right coronary angioplasty with stent placement. The patient’s course after angioplasty was uneventful. On the 15th hospital day, esophagogastroduodenoscopy revealed esophageal erosion and superficial gastritis. She was discharged on foot the following day. When physicians treat patients with hematemesis, electrocardiography and the measurement of troponin are essential before esophagogastroduodenoscopy.
Tropospheric Ozone Formation Estimation in Urban City, Bangi, Using Artificial Neural Network (ANN)
Authors: Abdul Aziz Fatin Aqilah Binti , Abd. Rahman Norliza , Mohd Ali Jarinah
Published: May 2019

Due to the rapid development of economy and society around the world, the most urban city is experiencing tropospheric ozone or commonly known as ground-level air pollutants. The concentration of air pollutants must be identified as an early precaution step by the local environmental or health agencies. This work aims to apply the artificial neural network (ANN) in estimating the ozone concentration forecast in Bangi. It consists of input variables such as temperature, relative humidity, concentration of nitrogen dioxide, time, UVA and UVB rays obtained from routine monitoring, and data recorded. Ten hidden layer is utilized to obtain the optimized ozone concentration, which is the output layer of the ANN framework. The finding showed that the meteorology condition and emission patterns play an important part in influencing the ozone concentration. However, a single network is sufficient enough to estimate the concentration despite any circumstances. Thus, it can be concluded that ANN is able to give reliable and satisfactory estimations of ozone concentration for the following day.
An Investigation on the Correlation between the Mechanical Properties of Human Skull Bone, Its Geometry, Microarchitectural Properties, and Water Content
Authors: Lee Jik Hang Clifford , Ondruschka Benjamin , Falland-Cheung Lisa , Scholze Mario , Hammer Niels , Tong Darryl Chan , Waddell John Neil
Published: May 2019

With increasingly detailed imaging and mechanical analysis, modalities need arises to update methodology and assessment criteria for skull bone analysis to understand how bone microarchitecture and the presence of attached tissues may affect the response to mechanical load. The main aim was to analyze the effect of macroscopic and microstructural features, as well as periosteal attachment, on the mechanical properties of human skull bone. Fifty-six skull specimens from ethanol-phenoxyethanol-embalmed cadavers were prepared from two human cadavers. Assuming symmetry of the skull, all samples from one-half each were stripped of periosteum and dura mater, while the soft tissues were kept intact on the remaining samples on the contralateral side. The specimens were analyzed using microcomputed tomography to assess trabecular connectivity density, total surface area, and volume ratio. The specimens were loaded under three-point bend tests until fracture with optical co-registration. The bone fragments were then lyophilized to measure their water content. With increasingly detailed imaging and mechanical analysis modalities, there is a need to update methodology and assessment criteria for skull bone analysis to understand how the bone microarchitecture and the presence of attached tissues may affect the response to mechanical load. The mechanical properties were negatively correlated to bone thickness and water content. Conversely, most microarchitectural features did not influence either mechanical parameter. The correlation between mechanical response data and morphologic properties remains similar between the results of embalmed tissues presented here and fresh osseous tissue from literature data. The findings presented here add to the existing methodology to assess human skull for research purposes. The interaction between most microarchitectural features in ethanol-phenoxyethanol-embalmed embalmed skull samples and bending stress appear to be minute.
Dynamical Analysis of the SEIB Model for Brucellosis Transmission to the Dairy Cows with Immunological Threshold
Authors: Zhang Wei , Zhang Juan , Wu Yong-Ping , Li Li
Published: May 2019

As we all know, bacteria is different from virus which with certain types can be killed by the immune cells in the body. The brucellosis, a bacterial disease, can invade the body by indirect transmission from environment, which has not been researched by combining with immune cells. Considering the effects of immune cells, we put a minimum infection dose of brucellosis invading into the dairy cows as an immunological threshold and get a switch model. In this paper, we accomplish a thorough dynamics analysis of a SEIB switch model. On the one hand, we can get a disease‐free and bacteria‐free steady state and up to three endemic steady states which may be thoroughly analyzed in different cases of a minimum infection dose in a switch model. On the other hand, we calculate the basic reproduction number R0 and know that the disease‐free and bacteria‐free steady state is a global stability when R0 < 1, and the one of the endemic steady state is a conditionally global stability when R0 > 1. We find that different amounts of R0 may lead to different steady states of brucellosis, and considering the effects of immunology is more serious in mathematics and biology.
Failure Mechanism and Mechanical Properties of a Retard‐Bonded Prestressed Concrete Girder While Curing
Authors: Sui Wei-ning , Wang Zi-yi , Zhao Zhong-hua , Wang Zhan-fei
Published: May 2019

The mechanical performance and failure mechanism of a retard‐bonded (RB) type prestressed concrete (PC) girder in different curing periods are investigated through four‐point loading experiments. Six RB‐type PC girder specimens with three RB prestressed tendons (PTs) along the longitudinal direction were fabricated. The measurements include the following: the retard‐bonded agent ages versus the load‐carrying capacity of the girder, the deflection of girder, the strain distribution at key cross sections through the girder, the pressure at PT tensile and anchoring ends, crack distribution, and so on. The experimental results indicate that when stretching the PT within proper tensile period, the retarder curing ages have less impact on the cracking load and a greater impact on the ultimate bending strength; the ultimate bending strength of the RB‐type PC girder increased with increased retarder curing. Nonetheless, stretching the PT after excessive retarder curing (after the retarder had solidified completely), the cracks in the PC girder’s pure bending segment are wider and less numerous, the ultimate bending strength of the girder is lower, and its ductility is poor.
Building Earthquake Damage Analysis Using Terrestrial Laser Scanning Data
Authors: Jiao Qisong , Jiang Hongbo , Li Qiang
Published: May 2019

Terrestrial laser scanners (TLSs) can acquire high‐precision three‐dimensional point cloud data for earthquake‐damaged buildings. In this study, we collected TLS data in the Wenchuan earthquake zone and developed the TLS‐BSAM (terrestrial laser scanning‐based building shape analysis model) to carry out a building earthquake damage analysis. This model involves equidistance polygon array extraction, shape dispersion parameter calculations, irregular building clustering segmentation, and damage analysis. We chose 21 buildings as samples for the experiments. The results show that when using an equidistance polygon array to depict a three‐dimensional building, 0.5 m is a reasonable sampling interval for building earthquake damage analysis. Using certain characteristic parameters to carry out K‐means clustering, one can efficiently divide irregular buildings into regular blocks. Then, by weighted averages, the shape dispersion parameters can be calculated to express the damage extent to buildings. Among the shape dispersion parameters, at least the weighted average standard deviations of the tilt direction, rectangularity, compactness, and center point are suitable to reflect the damage extent. Higher values reflect more serious damage. On the basis of existing data, the weighted average standard deviations of the tilt direction and center point can be used to establish discriminant functions that can effectively distinguish the damage extent.
Γδ T Cell-Based Immunotherapy in Melanoma: State of the Art
Authors: Toia F. , Di Stefano A. B. , Meraviglia S. , Lo Presti E. , Pirrello R. , Rinaldi G. , Fulfaro F. , Dieli F. , Cordova A.
Published: May 2019

Metastatic melanoma is still associated with a poor prognosis, and there is increasing interest in immunotherapy alone or in combination with other adjuvant therapies. Γδ T lymphocytes play a pivot role in the immune response against cancer, but while γδ-based immunotherapy is already a clinical reality for several solid tumors, data on melanoma are still limited and fragmented. This systematic review presents preclinical and clinical evidence for a role of γδ T lymphocytes in immunotherapeutic strategies for advanced melanoma and discusses research state of the art and future perspectives. Current strategies focus on in vivo stimulation, and ex vivo adoptive therapy and vaccination; results are promising, but further studies are needed to better investigate the interactions in tumoral microenvironment and to improve clinical efficacy of immunotherapeutic protocols.
The Broad-Spectrum Impact of Hidradenitis Suppurativa on Quality of Life: A Comparison with Psoriasis
Authors: Sampogna Francesca , Fania Luca , Mazzanti Cinzia , Caggiati Alessio , Pallotta Sabatino , Panebianco Annarita , Mastroeni Simona , Didona Biagio , Pintori Giusi , Abeni Damiano
Published: May 2019

Background/Aim: Hidradenitis suppurativa (HS) is a chronic skin disease with a heavy impact on patients’ quality of life (QoL). The aim of this study was to evaluate in detail the QoL impact of HS comparing it with other skin conditions, and in particular with psoriasis. Methods: Patients with a diagnosis of HS were recruited. QoL was measured using the Skindex-17 questionnaire. Results: Data were available for 69 HS patients. HS had the worst QoL among several skin conditions. Compared to psoriasis the mean symptom score was 69.4 versus 53.7, and the mean psychosocial score was 56.1 versus 32.7. Overall, the scores of patients with HS were higher than those of psoriasis patients on 16 of the 17 items of the Skindex-17. Conclusions: When compared to many different skin conditions, and in particular to psoriasis, HS was the most impairing condition, even at low levels of clinical severity.
Alzheimer’s Disease and Neurotransmission Gene Variants: Focus on Their Effects on Psychiatric Comorbidities and Inflammatory Parameters
Authors: Porcelli Stefano , Calabrò Marco , Crisafulli Concetta , Politis Antonis , Liappas Ioannis , Albani Diego , Raimondi Ilaria , Forloni Gianluigi , Benedetti Francesco , Papadimitriou George N. , Serretti Alessandro
Published: May 2019

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder accounting for 60–70% of dementia cases. Genetic origin accounts for 49–79% of disease risk. This paper aims to investigate the association of 17 polymorphisms within 7 genes involved in neurotransmission (COMT, HTR2A, PPP3CC, RORA, SIGMAR1, SIRT1, and SORBS3) and AD. Methods: A Greek and an Italian sample were investigated, for a total of 156 AD subjects and 301 healthy controls. Exploratory analyses on psychosis and depression comorbidities were performed, as well as on other available clinical and serological parameters. Results: AD was associated with rs4680 within the COMT gene in the total sample. Trends of association were found in the 2 subsamples. Some nominal associations were found for the depressive phenotype. rs10997871 and rs10997875 within SIRT1 were nominally associated with depression in the total sample and in the Greek subsample. rs174696 within COMT was associated with depression comorbidity in the Italian subsample. Discussion: Our data support the role of COMT, and particularly of rs4680, in the pathogenesis of AD. Furthermore, the SIRT1 gene seems to modulate depressive symptomatology in the AD population.
Role of Ancillary Techniques in Biliary Cytopathology Specimens
Authors: Layfield Lester
Published: May 2019

Biliary brushing cytology has become the standard of practice for the investigation of strictures of the biliary and pancreatic duct systems. The methodology however has a limitation in that it has low diagnostic sensitivity when only cytologic evaluation is used. A number of testing methodologies have been applied to brushing specimens in an attempt to improve overall sensitivity without loss of specificity. These have included DNA ploidy analysis, immunocytochemistry, individual gene mutational analysis, fluorescence in-situ hybridization (FISH), and next generation sequencing (NGS). Currently, FISH coupled with routine cytology appears to be the method of choice for improving diagnostic sensitivity. NGS shows significant promise for improvement of diagnostic sensitivity.
Malignant Pleural Effusion at Presentation in Patients with Small-Cell Lung Cancer
Authors: Shojaee Samira , Singh Inderjit , Solsky Ian , Nana-Sinkam Patrick
Published: May 2019

Background: Malignant pleural effusion (MPE) is commonly seen in patients with non-small cell lung cancer. However, the prevalence of MPE at presentation in small-cell lung cancer (SCLC) is not reported and the clinical impact of MPE at presentation on patients with SCLC remains largely unknown. Objective: The objective of this study is to assess the occurrence rate of MPE and its prognostic implications at presentation in patients with SCLC. Method: We used the Surveillance Epidemiology and End Results (SEER) registry to extract data from patients with SCLC diagnosed between 2004 and 2014. The Kaplan–Meier method was used to estimate the overall survival and the Cox proportional hazard model was used to evaluate whether MPE was an independent risk for outcome. Results: Among the 68,443 patients with SCLC, MPE was present in 7,639 (11.16%). The probability of MPE was higher in older patients with larger tumors and mediastinal lymph node involvement at presentation. Median overall survival (3 vs. 7 months), estimated 1-year survival (17 vs. 30%), and 2-year survival (6 vs. 14%) were significantly lower in patients with MPE than without MPE, respectively (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.41–1.50, p< 0.001). MPE was also an independent factor for worse survival in multivariate analysis (HR 1.36, 95% CI 1.32–1.41, p < 0.001). Conclusions: MPE is common at presentation (11%) in patients with SCLC and may be associated with decreased survival. Additional studies are required to assess the treatment-adjusted survival rate in the setting of MPE.
One-Year Results of Fixed Aflibercept Treatment Regime in Type 3 Neovascularization
Authors: Ernest Jan , Manethova Katerina , Kolar Petr , Sobisek Lukas , Sacconi Riccardo , Querques Giuseppe
Published: May 2019

Purpose: To evaluate the effect of intravitreal aflibercept injections in treatment-naive type 3 neovascularization using a fixed treatment regime during the first year of therapy. Methods: Fourteen eyes of 14 patients diagnosed with type 3 neovascularization were studied. All patients were treated with intravitreal aflibercept injections using a fixed treatment regime of 3 consecutive monthly dosages followed by 2-month interval injections. Results were assessed after a 12-month follow-up period. Changes of best corrected visual acuity (BCVA), central retinal thickness (CRT), central macular volume (CMV), and retinal pigment epithelium (RPE) atrophy at fundus autofluorescence and infrared reflectance images were recorded and analyzed. Results: BCVA improved from 60.3 ± 11.7 ETDRS letters at the baseline to 70.9 ± 10.3 ETDRS letters at 12-months follow-up (p = 0.036). Also, CRT and CMV statistically improved after the treatment (from 425 ± 117 to 308 ± 117 µm [p = 0.031] and from 9.52 ± 1.90 to 8.29 ± 0.95 mm3 [p = 0.073], respectively). In 4 patients, development and progression of RPE atrophy were observed, and it was associated with the presence of serous pigment epithelium detachment at the baseline. Furthermore, the development of a fibrotic lesion eccentric to the fovea was observed in 5 patients, without significant impairment of BCVA (p = 0.290). Conclusion: Intravitreal aflibercept administered in a fixed treatment regime during the first year of therapy may be effective for the improvement and stabilization of BCVA in eyes with type 3 neovascularization. However, RPE atrophy and subretinal/intraretinal fibrosis can develop during the treatment.
Duodenal Crohn’s Disease Complicated by Pancreatitis and Common Bile Duct Obstruction
Authors: Sousa Mafalda , Proença Luísa , Carlos Silva João , Ribeiro Gomes Ana Catarina , Afeto Edgar , Carvalho João
Published: May 2019

Introduction: Crohn’s disease (CD) is characterized by segmental and transmural involvement of any portion of the gastrointestinal tract from the mouth to the anus. Duodenal CD is a rare clinical entity, with the majority of the patients being symptomless – its diagnosis requires a high level of clinical suspicion. Case Presentation: We present the case of a 29-year-old male patient with a 2-month history of weight loss, epigastric pain and postprandial vomiting. He underwent upper endoscopy, which revealed a circumferential duodenal ulcer causing non-transposable luminal stenosis and was medicated with proton pump inhibitors. While awaiting gastroenterology consultation, he presented at the emergency department for sudden onset of abdominal pain with dorsal irradiation, nausea and vomiting. Laboratory tests showed anaemia and increased liver enzymes, amylase and lipase. Abdominal computed tomography showed ectasia of the common bile duct (CBD) and intrahepatic biliary tract and a small amount of gas in the main pancreatic duct associated with duodenal thickening. The case was interpreted as probable CD complicated by pancreatitis and obstruction of the CBD, and he was hospitalized under antibiotic therapy and hydrocortisone with improvement of the condition. After discharge, he underwent colonoscopy that revealed several ulcers in the ileum and magnetic resonance imaging that showed distension of the stomach with reduction of the calibre of the transition from the duodenal bulb to the second portion of the duodenum in a 10- to 15-mm extension, as well as associated dilatation of the intrahepatic bile ducts and CBD and diffuse and regular ectasia of the main pancreatic duct. Combination therapy with azathioprine and infliximab was initiated; the patient presented clinical response at 12 weeks and endoscopic/imaging remission at 9 months. Discussion/Conclusion: Hepatobiliary and pancreatic manifestations are common in CD patients involving multiple mechanisms. In this case report, we pre­sent a patient with duodenal CD complicated with pancreatitis and CBD obstruction due to distortion phenomena by duodenal stenosis, a condition that is rarely described.
Low-Intensity Exercise Suppresses CCAAT/Enhancer-Binding Protein δ/Myostatin Pathway Through Androgen Receptor in Muscle Cells
Authors: Son Bo-Kyung , Eto Masato , Oura Miya , Ishida Yuki , Taniguchi Sakiko , Ito Koichi , Umeda-Kameyama Yumi , Kojima Taro , Akishita Masahiro
Published: May 2019

Background: Androgen production following exercise has been suggested to contribute anabolic actions of muscle. However, the underlying mechanisms of the androgen receptor (AR) in androgen’s action are still unclear. Objective: In the present study, we examined androgen/AR-mediated action in exercise, especially for the suppression of myostatin, a potent negative regulator of muscle mass. Methods: To examine the effects of exercise, we employed low-intensity exercise in mice and electric pulse stimulation (EPS) in C2C12 myotubes. Androgen production by C2C12 myotubes was measured by enzyme-linked immunosorbent assay. To block the action of AR, we pretreated C2C12 myotubes with flutamide. Quantitative real-time polymerase chain reaction was used to determine the expression levels of proteolytic genes including CCAAT/enhancer-binding protein delta (C/EBPδ), myostatin and muscle E3 ubiquitin ligases, as well as myogenic genes such as myogenin and PGC1α. The activation of 5′-adenosine-activated protein kinase and STAT3 was determined by Western blot analysis. Results: Both mRNA and protein levels of AR significantly increased in skeletal muscle of low-intensity exercised mice and C2C12 myotubes exposed to EPS. Production of testosterone and dihydrotestosterone from EPS-treated C2C12 myotubes was markedly increased. Of interest, we found that myostatin was clearly inhibited by EPS, and its inhibition was significantly abrogated when AR was blocked by flutamide. To test how AR suppresses myostatin, we examined the effects of EPS on C/EBPδ because the promoter region of myostatin has several C/EBP recognition sites. C/EBPδ expression was decreased by EPS, and this decrease was negated by flutamide. IL-6 and phospho-STAT3 (pSTAT3) expression, the downstream pathway of myostatin, were decreased by EPS and this was also reversed by flutamide. Similar downregulation of C/EBPδ, myostatin, and IL-6 was seen in skeletal muscle of low-intensity exercised mice. Conclusions: Muscle AR expression and androgen production were increased by exercise and EPS treatment. As a mechanistical insight, it is suggested that AR inhibited myostatin expression transcriptionally by C/EBPδ suppression, which negatively influences IL-6/pSTAT3 expression and consequently contributes to the prevention of muscle proteolysis during exercise.
Production of Vowels by Electrolaryngeal Speakers Using Clear Speech
Authors: Cox Steven R. , Raphael Lawrence J. , Doyle Philip C.
Published: May 2019

Background/Aims: This study examined the effect of clear speech on vowel productions by electrolaryngeal speakers. Method: Ten electrolaryngeal speakers produced eighteen words containing /i/, /ɪ/, /ɛ/, /æ/, /eɪ/, and /oʊ/ using habitual speech and clear speech. Twelve listeners transcribed 360 words, and a total of 4,320 vowel stimuli across speaking conditions, speakers, and listeners were analyzed. Analyses included listeners’ identifications of vowels, vowel duration, and vowel formant relationships. Results: No significant effect of speaking condition was found on vowel identification. Specifically, 85.4% of the vowels were identified in habitual speech, and 82.7% of the vowels were identified in clear speech. However, clear speech was found to have a significant effect on vowel durations. The mean vowel duration in the 17 consonant-vowel-consonant words was 333 ms in habitual speech and 354 ms in clear speech. The mean vowel duration in the single consonant-vowel words was 551 ms in habitual speech and 629 ms in clear speech. Conclusion: Finding suggests that, although clear speech facilitates longer vowel durations, electrolaryngeal speakers may not gain a clear speech benefit relative to listeners’ vowel identifications.
Two-Year Follow-Up after Treatment with the Cognitive Behavioral Analysis System of Psychotherapy versus Supportive Psychotherapy for Early-Onset Chronic Depression
Authors: Schramm Elisabeth , Kriston Levente , Elsaesser Moritz , Fangmeier Thomas , Meister Ramona , Bausch Paul , Zobel Ingo , Bailer Josef , Wambach Katrin , Backenstrass Matthias , Klein Jan Philipp , Schoepf Dieter , Schnell Knut , Gumz Antje , Löwe Bernd , Walter Henrik , Wolf Markus , Domschke Katharina , Berger Mathias , Hautzinger Martin , Härter Martin
Published: May 2019

Background: Evidence on the long-term efficacy of psychotherapeutic approaches for chronic depression is scarce. Objective: To evaluate the effects of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) compared to Supportive Psychotherapy (SP) 1 year and 2 years after treatment termination. Methods: In this study, we present 1- and 2-year follow-up assessments of a prospective, multicenter, evaluator-blinded, randomized clinical trial of outpatients with early-onset chronic major depression (n = 268). The initial treatment included 32 sessions of CBASP or SP over 48 weeks. The primary outcome was the rate of “well weeks” (Longitudinal Interval Follow-Up Evaluation; no/minimal symptoms) after 1 year and 2 years. The secondary outcomes were, among others, clinician- and self-rated depressive symptoms, response/remission rates, and quality of life. Results: Of the 268 randomized patients, 207 (77%) participated in the follow-up. In the intention-to-treat analysis, there was no statistically significant difference between CBASP and SP patients in experiencing well weeks (CBASP: mean [SD] of 48.6 [36.9] weeks; SP: 39.0 [34.8]; rate ratio 1.26, 95% CI 0.99–1.59, p = 0.057, d = 0.18) and in remission rates (CBASP: 1 year 40%, 2 years 40.2%; SP: 1 year 28.9%, 2 years 33%) in the 2 years after treatment. Statistically significant effects were found in favor of CBASP 1 year after treatment termination regarding the rate of well weeks, self-rated depressive symptoms, and depression-related quality of life. Conclusions: CBASP lost its superiority over SP at some point between the first and the second year. This suggests the necessity of maintenance treatment for early-onset chronically depressed patients remitted with CBASP during the acute therapy phase, as well as the sequential integration of other treatment strategies, including medication for those who did not reach remission.
Management of Traumatic Lower-Eyelid Avulsion and Complete Loss of the Lacrimal Canaliculus: A Case Report
Authors: Hawlina Gregor , Vergot Katarina
Published: May 2019

Eyelid injuries commonly occur as a result of blunt or sharp periocular trauma. When the medial canthal region is affected, injury can be associated with canalicular laceration or avulsion. Complete loss of the lacrimal canaliculus associated with epiphora is a challenging condition, and reconstruction often leads to poor and disappointing results. Surgical treatment of a patient following blunt facial trauma that resulted in medial avulsion of the lower eyelid with tissue loss is presented. A 72-year-old male patient presented with avulsion of the medial 2/3 of the left lower eyelid together with complete loss of the inferior canaliculus. Eyelid tissue was not preserved. The inferior canaliculus was reconstructed using a Mini Monoka (FCI Ophthalmics), which was sutured under the caruncle and was enveloped with surrounding tissue. Loss of the lower eyelid tissue was substituted with a medially shifted Hughes flap and free skin transplant from the ipsilateral upper eyelid. The Hughes flap was divided after 2 weeks, while the Mini Monoka extruded spontaneously approximately 3 months after the injury. Ten months after the injury, the opening of the reconstructed lower canaliculus was positioned under the caruncle and was patent on probing and syringing. The patient is without epiphora and is satisfied with the functional and aesthetic result. In eyelid injuries we follow certain rules of reconstruction, but each case is unique and requires some inventiveness. The idea of inferior canalicular reconstruction following lower-eyelid avulsion with tissue loss is presented.