bluuebunny/crossref_metadata_2025 huggingface dataset:
Native valve endocarditis caused byLactococcus garvieae: an emerging human pathogen
Authors: Lim Felicia H , Jenkins David R
Published: May 2017

A 57-year-old man presented with native mitral valve endocarditis caused byLactococcus garvieae, a known animal pathogen that is increasingly being reported as a cause of human infections. The organism was cultured in four sets of blood cultures and identification was initially made by matrix-assisted laser desorption/ionisation—time of flight mass spectrometry and confirmed by 16S rDNA PCR of the blood culture isolate. He was successfully treated with 6 weeks of both amoxicillin and gentamicin and underwent valve replacement surgery after 4 weeks of antimicrobial treatment. The removed valve was sterile butL. garvieaeDNA was detected on the valve using 16S rDNA PCR. The cause of theL. garvieaeinfection could not be ascertained but flexible sigmoidoscopy demonstrated colonic polyps, which have been linked to infection with this organism.
Update on cell therapy for stroke
Authors: Kenmuir Cynthia L , Wechsler Lawrence R
Published: May 2017

Ischaemic stroke remains a leading cause of death and disability. Current stroke treatment options aim to minimise the damage from a pending stroke during the acute stroke period using intravenous thrombolytics and endovascular thrombectomy; however, there are no currently approved treatment options for reversing neurological damage once a stroke is completed. Preclinical studies suggest that cell therapy may be safe and effective in improving functional outcomes. Several recent clinical trials have reported safety and some improvement in outcomes following cell therapy administration in ischaemic stroke, which are reviewed. Cell therapy may provide a promising new treatment for stroke reducing stroke-related disability. Further investigation is needed to determine specific effects of cell therapy and to optimise cell delivery methods, cell dosing, type of cells used, timing of delivery, infarct size and location of infarct that are likely to benefit from cell therapy.
Long-term application of organic matter based fertilisers: Advantages or risks for soil biota? A review
Authors: Hlava Jakub , Száková Jiřina , Vadlejch Jaroslav , Čadková Zuzana , Balík Jiří , Tlustoš Pavel
Published: May 2017

The addition of organic matter rich materials to agricultural soil is currently a common practice to improve its quality and fertility. However, the input of organic matter rich waste materials into soils significantly impacts ecosystem functions. The potential contamination of soil by various chemical compounds is one of the many risks that should be taken into account. Recent environmental studies have assessed the introduction of potentially hazardous compounds from pharmaceutical and personal care products, heavy metals, and other sources. This review summarizes knowledge concerning the influence of long-term soil fertilisation on soil biota, with special attention to soil nematodes. The interaction between fertilisers and soil organisms is highly complex. Nematode communities can be used as an ecosystem assessment tool to provide a holistic measure of the biotic and functional status of soils. However, extensive investigation of nematode interaction with the affected soil, and the physicochemical characteristics of the soil, should elucidate their role as one of the components in the feedback cycle controlling ecosystem processes.
Fine-tuning problems in quantum field theory and Lorentz invariance: A scalar-fermion model with a physical momentum cutoff
Authors: Cortés J. L. , López-Sarrión Justo
Published: May 2017

In this paper, we study the consistency of having Lorentz invariance as a low energy approximation within the quantum field theory framework. A model with a scalar and a fermion field is used to show how a Lorentz invariance violating high momentum scale, a physical cutoff rendering the quantum field theory finite, can be made compatible with a suppression of Lorentz invariance violations at low momenta. The fine tuning required to get this suppression and to have a light scalar particle in the spectrum are determined at one loop.
Numerical analysis on temperature field in single-wire flux-aided backing-submerged arc welding
Authors: Pu Juan , Wu Ming Fang , Pan Haichao
Published: May 2017

Single-wire flux-aided backing-submerged arc welding (FAB-SAW) technology has been widely used to weld thick steel plate due to its easy assembly and high heat input. The microstructure and property of welded joint are closely related to the thermal field of FAB-SAW process. In this research, the feature of thermal field for single-wire FAB-SAW was investigated. Based on the heat transfer mechanism, a three-dimensional transient model for thermal field was developed based on the influence of steel thickness, groove angle and ceramic backing. The temperature profile in single-wire FAB-SAW of D36 steel under different welding conditions was simulated by ANSYS. The characteristic of thermal field was analyzed and the influences of groove angle on temperature field for different plate thicknesses were discussed. The calculated geometries and dimensions of weld cross-section under different conditions show a good agreement with the experimental results. This newly built model can describe the thermal field accurately, which would be helpful to understanding the thermophysical mechanism of FAB-SAW and optimizing the welding process.
Deformed space–time transformations in Mercury
Authors: Cardone F. , Albertini G. , Bassani D. , Cherubini G. , Guerriero E. , Mignani R. , Monti M. , Petrucci A. , Ridolfi F. , Rosada A. , Rosetto F. , Sala V. , Santoro E. , Spera G.
Published: May 2017

A mole of Mercury was suitably treated by ultrasound in order to generate in it the same conditions of local Lorentz invariance violation that were generated in a sonicated cylindrical bar of AISI 304 steel and that are the cause of neutron emission during the sonication. After 3 min, part of the mercury turned into a solid material which turned out to contain isotopes having a different mass (higher and lower) with respect to the isotopes already present in the initial material (mercury). These transformations in the atomic weight without gamma production above the background are brought about during Deformed Space–Time reactions. We present the results of the analyses performed on samples taken from the transformation product. The analyses have been done in two groups, the first one using five different analytical techniques: ICP-OES, XRF, ESEM-EDS, ICP-MS, INAA. In the second group of analyses, we used only two techniques: INAA and ICP-MS. The second group of analyses confirmed the occurring of the transformations in mercury.
Time evolution of entropy for spherical self-gravitating systems
Authors: Sui Ning , He Ping
Published: May 2017

In this work, we investigate the dynamical evolution of spherical self-gravitating systems under their own gravity with [Formula: see text]-body simulations. For this purpose, we study the evolution of the generalized virialization relations, and particularly focus on the time evolution of the coarse-grained entropy of dark matter halos under various perturbations. First, we construct six single perturbation models under four initial conditions to mimic typical disturbances that a realistic gravitating system may encounter. With the simulation results, we show the time evolution of the entropy for the six perturbation models. In all these models, at first the entropy increases rapidly for a short period of time, slowly evolves for a longer period of time and then remains nearly unchanged in the subsequent evolution. The main dynamical mechanisms behind these evolutions should be violent relaxation and phase mixing. However, under repeated perturbations to the system, the evolution of entropy of self-gravitating systems manifests complete differences from that of the usual thermodynamical systems. We see that the entropy of the end states of every single perturbation, according to different repeated perturbation modes, either decreases or increases. We argue that the increasing or decreasing of the end-state entropy should be the reflection of the complexity of the thermodynamical states of self-gravitating systems. These conclusions are independent of the initial conditions. Besides, we demonstrate that the generalized virialization relations can reveal whether or not, or in which radius interval, the collisionless Boltzmann equation is suitable for description of a self-gravitating system, and can be used as good stability criteria of the system.
The Effect of FASB Statement No. 123R on Stock Repurchases: An Empirical Examination of Management Incentives
Authors: Hegemann Steven , Ismailescu Iuliana
Published: May 2017

This study examines management’s response to the change in accounting for stock option-based compensation imposed by SFAS No. 123R, whose implementation is expected to reduce reported income. To cope with this impact, management may be motivated to decrease the use of stock options as part of compensating employees and engage in stock repurchases in an attempt to increase the value of outstanding employee stock options. Our findings demonstrate a significant negative relation between stock options granted and shares repurchased in the aftermath of SFAS No. 123R, particularly for the S&P 500 firms known for their heavy use of employee stock options. Furthermore, evidence of a contemporaneous increase in repurchases and leverage in the post SFAS 123R period may suggest that some of the buybacks may have been funded with debt. Our findings are robust to the inclusion of traditional determinants of share repurchases.
Analysis and Optimal Design of Stress Wave Intensity Attenuation in Layered Structures
Authors: Rafiee-Dehkharghani R. , Bansal Dipanshu , Aref Amjad J. , Dargush Gary F.
Published: May 2017

Within the framework of linear two-dimensional elastodynamics, stress wave intensity attenuators are studied under material and boundary condition discontinuities collectively. The influence of various parameters on the efficiency of stress wave attenuators is investigated thoroughly and a comprehensive understanding of the response is developed under dynamic loadings for a wide range of frequencies. In particular, the effect of in-plane and out-of-plane dimensions, incident wave frequencies (wavelength), rigidity of the host structure, and impedance mismatch between different layers have been examined. The dependence of stress wave attenuator efficiency and robustness are found to be a complex function of all relevant parameters, and performance is observed to vary significantly for various combinations. To illustrate the significance of combined effects of various parameters on the potential efficiency of the stress wave intensity attenuators, an optimization problem is solved. An optimal material set-up of a 12-layered structure, subjected to transient loadings with varying durations and wide range of frequency contents, is presented. A coupled genetic algorithm-finite element methodology is developed specifically for the optimal design of layered structures. This methodology is highly suitable for investigating the solution space that is too large to be explored by an exhaustive parametric study. The results of the optimal designs evidently show that the efficiency of the stress wave attenuators depends significantly on the duration of transient loading, and high efficiency can be attained for short durations.
In vivosilymarin’s antioxidant and anti-apoptotic effects on photodynamic therapy’s responsiveness
Authors: Dionisie Vlad , Clichici Simona , Ion Rodica M. , Danila Oana O. , Moldovan Remus , Decea Nicoleta , Gheban Dan , Olteanu Florin Catalin , Filip Gabriela A.
Published: May 2017

Several studies have shown that some anti-oxidant natural compounds in combination with photodynamic therapy (PDT) can enhance the effectiveness of treatment. The aim of this study is to evaluate the effect of silymarin (SIL) in combination with 5,10,15,20-tetra-sulphonato-phenyl-porphyrin (TSPP) based photodynamic therapy, on experimental tumors. 30 Wistar rats with Walker carcinosarcoma, were divided into 6 groups: group 0 (control) — control, untreated group; group 1 (TSPP) — one dose of TSPP; group 2 (SIL) — silymarin; group 3 (PDT) — TSPP and irradiation 24 h after; group 4 (SIL[Formula: see text]PDT) — silymarin, TSPP and irradiation 24 h after; group 5 (SIL[Formula: see text]IR) and group 6 (IR) — irradiation and in addition, group 5 received SIL. Silymarin administered before photodynamic therapy decreased the lipid peroxidation ([Formula: see text] < 0.05) and modulated the antioxidant defense in tumor treated with PDT and silymarin suggesting that silymarin administration along with photodynamic therapy has an anti-oxidant effect. The caspase — 8 level and -3 activity increased in PDT and PDT [Formula: see text] SIL groups compared to the control; between the two groups there was a significant difference in term of apoptosis in favor to PDT. In conclusion, silymarin administration inhibited the reactive oxygen species generation and reduced the tumoral cells’ apoptosis, suggesting that natural compound administered before photodynamic therapy did not improve the therapy’s effect.
POLOCALC: A Novel Method to Measure the Absolute Polarization Orientation of the Cosmic Microwave Background
Authors: Nati Federico , Devlin Mark J. , Gerbino Martina , Johnson Bradley R. , Keating Brian , Pagano Luca , Teply Grant
Published: May 2017

We describe a novel method to measure the absolute orientation of the polarization plane of the Cosmic Microwave Background (CMB) photons with arcsecond accuracy, enabling unprecedented measurements for cosmology and fundamental physics. Existing and planned CMB polarization instruments looking for primordial B-mode signals need an independent, experimental method for systematics control on the absolute polarization orientation. The lack of such a method limits the accuracy of the detection of inflationary gravitational waves, the constraining power on the neutrino sector through measurements of gravitational lensing of the CMB, the possibility of detecting Cosmic Birefringence (CB), and the ability to measure primordial magnetic fields. Sky signals used for calibration and direct measurements of the detector orientation cannot provide an accuracy better than 1[Formula: see text]. Self-calibration methods provide better accuracy, but may be affected by foreground signals and rely heavily on model assumptions, losing constraining power on fundamental processes, like CB, Faraday Rotation and chiral gravity models. The POLarization Orientation CALibrator for Cosmology, POLOCALC, will dramatically improve instrumental accuracy by means of an artificial calibration source flying on high-altitude balloons and aerial drones. Polarization angle calibration requires observation of a well-characterized distant source at high elevation angles. A balloon-borne calibrator will provide a source in the far field of larger telescopes, while an aerial drone can be used for tests and smaller polarimeters. POLOCALC will also allow a unique method to measure the telescopes’ polarized beam. Even a two-hour balloon flight will allow enough time to perform polarization angle calibration and polarized beam function measurements. The source will make use of both narrow and broadband microwave emitters between 40[Formula: see text]GHz and 150[Formula: see text]GHz coupled to precise polarizing filters. The orientation of the source polarization plane will be registered to absolute celestial coordinates by star cameras and gyroscopes with arcsecond accuracy. This project can become a rung in the calibration ladder for the field: any existing or future CMB polarization experiment observing our novel polarization calibrator will enable measurements of the polarization angle for each detector with respect to absolute sky coordinates.
Suprascapular Nerve Entrapment Caused by Protrusion of an Intraosseous Ganglion of the Glenoid into the Spinoglenoid Notch: A Rare Cause of Posterior Shoulder Pain
Authors: Ishimaru Daichi , Nagano Akihito , Terabayashi Nobuo , Nishimoto Yutaka , Akiyama Haruhiko
Published: May 2017

We describe a case of suprascapular nerve entrapment caused by protrusion of an intraosseous ganglion of the glenoid into the spinoglenoid notch. A 47-year-old man with left shoulder pain developed an intraosseous cyst in the left glenoid, which came into contact with the suprascapular nerve. The area at which the patient experienced spontaneous shoulder pain was innervated by the suprascapular nerve, and 1% xylocaine injection into the spinoglenoid notch under ultrasonographic guidance relieved the pain. Therefore, we concluded that the protrusion of an intraosseous cyst of the glenoid into the spinoglenoid notch was a cause of the pain, and performed curettage. Consequently, the shoulder pain was resolved promptly without suprascapular nerve complications, and the cyst was histologically diagnosed as an intraosseous ganglion. This case demonstrated that the intraosseous ganglion of the glenoid was a benign lesion but could be a cause of suprascapular nerve entrapment syndrome. Curettage is a useful treatment option for a ganglion inside bone and very close to the suprascapular nerve.
Unusual Case of Extraction of Maxillary Lateral Incisors and Mandibular Central Incisors
Authors: Yañez-Vico Rosa-María , Cadenas de Llano-Perula Maria , Solano-Reina Enrique
Published: May 2017

Introduction. This article’s purpose is to report a case where maxillary lateral incisors and mandibular central incisors are extracted and a canine substitution was performed as the best therapeutic option in order to obtain symmetry in a malocclusion with an upper lateral incisor with poor prognostic, solve moderate crowding, get enough space for the permanent dentition, and provide stability to the results.Case Report. An 11-year-old boy with straight profile with acute-to-normal nasolabial angle and protruded lips, mixed dentition, lower and upper severe crowding, and a bilateral molar angle Class I. The left maxillary lateral incisor failed endodontic treatment secondary to an intrusive traumatic lesion in the primary and permanent dentition. The treatment of choice was the extraction of both upper lateral incisors and both central lower incisors. The patient finished with molar and canine angle Class I and coincident midlines and was functionally stable; both lateral and protrusive jaw movements were effectively made by the first premolars and central incisors and canines without improper contacts of the rest of the teeth. Overbite of one-third and correct overjet were also achieved, and the esthetic outcome was satisfactory due to the composed material restorations of both the central and lateral incisors, as well as recontouring of the first maxillary premolars.
A Coupled 1D-2D Hydrodynamic Model for Urban Flood Inundation
Authors: Fan Yuyan , Ao Tianqi , Yu Haijun , Huang Guoru , Li Xiaodong
Published: May 2017

Hydrodynamic models were commonly used for flood risk management in urban area. This paper presents initial efforts in developing an urban flood inundation model by coupling a one-dimensional (1D) model with a two-dimensional (2D) model to overcome the drawbacks of each individual modelling approach, and an additional module is used to simulate the rainfall-runoff process in study areas. For the 1D model, the finite difference method is used to discretize the Saint-Venant equations. An implicit dual time-stepping method (DTS) is then applied to a 2D finite volume model for an inundation simulation to improve computational efficiency. A total of four test cases are applied to validate the proposed model; its performance is demonstrated by a comparison with an explicit scheme and previously published results (an extensive physical experiment benchmark case, a vertical linking example, and two real drainage cases with actual topography). Results demonstrate that the proposed model is accurate and efficient in simulating urban floods for practical applications.
Measuring Hydrometeors with a Precipitation Microphysical Characteristics Sensor: Calibration and Field Measurements
Authors: Hu Yuntao , Liu Xichuan , Gao Taichang , Shu Xiaojian
Published: May 2017

Aiming at the simultaneous measurement of the size, shape, and fall velocity of precipitation particles in the natural environment, we present here a new ground-based precipitation microphysical characteristics sensor (PMCS) based on the particle imaging velocimetry technology. The PMCS can capture autocorrelated images of precipitation particles by double-exposure in one frame, by which the size, axis ratio, and fall velocity of precipitation particles can be calculated. The PMCS is calibrated by a series of glass balls with certain diameters under varying light conditions, and a self-adaptive threshold method is proposed. The shape, axis ratio, and fall velocity of raindrops were calculated and discussed based on the field measurement results of PMCS. The typical shape of large raindrop is an oblate ellipsoid, the axis ratio of raindrops decreases linearly with the diameter, the fall velocity of raindrops approaches its asymptote, and the above observed results are in good agreement with the empirical models; the synchronous observation of a PMCS, an OTT PARSIVEL disdrometer, and a rain gauge shows that the PMCS is able to measure the rain intensity, accumulated rainfall, and drop size distribution with high accuracy. These results have validated the performance of PMCS.
Highly Sensitive Colorimetric Assay for Determining Fe3+Based on Gold Nanoparticles Conjugated with Glycol Chitosan
Authors: Kim Kyungmin , Nam Yun-Sik , Lee Yeonhee , Lee Kang-Bong
Published: May 2017

A highly sensitive and simple colorimetric assay for the detection of Fe3+ions was developed using gold nanoparticles (AuNPs) conjugated with glycol chitosan (GC). The Fe3+ion coordinates with the oxygen atoms of GC in a hexadentate manner (O-Fe3+-O), decreasing the interparticle distance and inducing aggregation. Time-of-flight secondary ion mass spectrometry showed that the bound Fe3+was coordinated to the oxygen atoms of the ethylene glycol in GC, which resulted in a significant color change from light red to dark midnight blue due to aggregation. Using this GC-AuNP probe, the quantitative determination of Fe3+in biological, environmental, and pharmaceutical samples could be achieved by the naked eye and spectrophotometric methods. Sensitive response and pronounced color change of the GC-AuNPs in the presence of Fe3+were optimized at pH 6, 70°C, and 300 mM NaCl concentration. The absorption intensity ratio (A700/A510) linearly correlated to the Fe3+concentration in the linear range of 0–180 μM. The limits of detection were 11.3, 29.2, and 46.0 nM for tap water, pond water, and iron supplement tablets, respectively. Owing to its facile and sensitive nature, this assay method for Fe3+ions can be applied to the analysis of drinking water and pharmaceutical samples.
Evidence of Divergent Amino Acid Usage in Comparative Analyses of R5- and X4-Associated HIV-1 Vpr Sequences
Authors: Antell Gregory C. , Dampier Will , Aiamkitsumrit Benjamas , Nonnemacher Michael R. , Pirrone Vanessa , Zhong Wen , Kercher Katherine , Passic Shendra , Williams Jean , Liu Yucheng , James Tony , Jacobson Jeffrey M. , Szep Zsofia , Wigdahl Brian , Krebs Fred C.
Published: May 2017

Vpr is an HIV-1 accessory protein that plays numerous roles during viral replication, and some of which are cell type dependent. To test the hypothesis that HIV-1 tropism extends beyond the envelope into thevprgene, studies were performed to identify the associations between coreceptor usage and Vpr variation in HIV-1-infected patients. Colinear HIV-1 Env-V3 and Vpr amino acid sequences were obtained from the LANL HIV-1 sequence database and from well-suppressed patients in the Drexel/Temple Medicine CNS AIDS Research and Eradication Study (CARES) Cohort. Genotypic classification of Env-V3 sequences as X4 (CXCR4-utilizing) or R5 (CCR5-utilizing) was used to group colinear Vpr sequences. To reveal the sequences associated with a specific coreceptor usage genotype, Vpr amino acid sequences were assessed for amino acid diversity and Jensen-Shannon divergence between the two groups. Five amino acid alphabets were used to comprehensively examine the impact of amino acid substitutions involving side chains with similar physiochemical properties. Positions 36, 37, 41, 89, and 96 of Vpr were characterized by statistically significant divergence across multiple alphabets when X4 and R5 sequence groups were compared. In addition, consensus amino acid switches were found at positions 37 and 41 in comparisons of the R5 and X4 sequence populations. These results suggest an evolutionary link between Vpr and gp120 in HIV-1-infected patients.
Tubulin Beta‐3 Chain as a New Candidate Protein Biomarker of Human Skin Aging: A Preliminary Study
Authors: Lehmann Sylvia G. , Bourgoin-Voillard Sandrine , Seve Michel , Rachidi Walid
Published: May 2017

Skin aging is a complex process, and a lot of efforts have been made to identify new and specific targets that could help to diagnose, prevent, and treat skin aging. Several studies concerning skin aging have analyzed the changes in gene expression, and very few investigations have been performed at the protein level. Moreover, none of these proteomic studies has used a global quantitative labeled proteomic offgel approach that allows a more accurate description of aging phenotype. We applied such an approach on human primary keratinocytes obtained from sun‐nonexposed skin biopsies of young and elderly women. A total of 517 unique proteins were identified, and 58 proteins were significantly differentially expressed with 40 that were downregulated and 18 upregulated with aging. Gene ontology and pathway analysis performed on these 58 putative biomarkers of skin aging evidenced that these dysregulated proteins were mostly involved in metabolism and cellular processes such as cell cycle and signaling pathways. Change of expression of tubulin beta‐3 chain was confirmed by western blot on samples originated from several donors. Thus, this study suggested the tubulin beta‐3 chain has a promising biomarker in skin aging.
Impact of Obesity on Serum Levels of Thyroid Hormones among Euthyroid Saudi Adults
Authors: Al-Musa Hassan M.
Published: May 2017

Aim of Study. To assess serum thyroid hormones levels among Saudi adults and to correlate participants’ serum levels with their grades of body mass index (BMI).Methodology. A total of 278 adult subjects were recruited. Participants were categorized according to their BMI grades into normal weight (BMI < 25 kg/m2), overweight (BMI 25–29.9 kg/m2), or obese (BMI≥30 kg/m2). Serum thyroid hormones levels were assessed at the central laboratory of Aseer Central Hospital, Abha City, by chemiluminescence immunoassay.Results. More than three-fourths of participants were either overweight (31.3%) or obese (44.6%). Mean TSH serum levels showed a significantly increasing trend with increasing BMI (p<0.001). A negative trend was observed regarding participants’ mean serum levels of fT4 with their BMI, but there were no significant differences in mean serum fT4 levels according to BMI. Moreover, no significant differences were observed in serum fT3 levels according to BMI.Conclusions. Mean TSH serum levels increase with BMI increase. Further largescale multicentric and longitudinal studies are necessary to prove the association between serum levels of thyroid hormones and BMI of euthyroid adults.
A Discussion of High-Risk HPV in a 6-Year-Old Female Survivor of Child Sexual Abuse
Authors: Cao Connie D. , Merjanian Lena , Pierre Joelle , Balica Adrian
Published: May 2017

Background. Human papilloma viruses (HPVs) cause a variety of clinical manifestations in children including skin warts, laryngeal papillomas, and condyloma acuminatum. Whereas the mode of transmission is well understood and management of HPV infection is clearly defined by guidelines in adults, less is known about the mode of transmission, natural history of disease, and appropriate management of high-risk anogenital HPV infections in children. Case. The patient is a previously healthy 6-year-old female who presented with multiple vaginal lesions causing pain and discomfort and was diagnosed with HPV 18 positive CIN I. Summary and Conclusion. Children infected with high-risk HPV subtypes remain a vulnerable patient population, and there is minimal literature on the natural history of disease and effects of overtreatment. Based on a literature review, conservative management, HPV vaccination, and consideration of the cervical cancer screening guidelines for adolescent females are an appropriate treatment course until more studies are reported on cervical cancer screening in survivors of child sexual abuse.
Histopathological and Reproductive Evaluation in Male Rats Fed Jatropha curcas Seed Cake with or without Alkaline Hydrolysis and Subjected to Heat Treatment
Authors: Teixeira Sousa Moura Laiane , Palomaris Mariano Souza Domenica , Mendonça Simone , de Aquino Ribeiro José Antônio , Fernandes Sousa Luciano , Tony Ramos Adriano , Maiorka Paulo César , de Araújo Vera Lúcia , Mayumi Maruo Viviane
Published: May 2017

Jatropha curcas cake, a by-product of biodiesel production, is rich in protein and has potential to be used in livestock feed; however, the presence of antinutritional factors and phorbol esters limits its use. Thus, this study investigated toxicological and reproductive effects in male Wistar rats after subchronic exposure to J. curcas cake subjected to detoxification procedures. Rats were divided into seven groups (n=10) and treated for 60 days. The control group received commercial feed, while experimental groups received a diet containing 5% J. curcas cake nonhydrolyzed or hydrolyzed with 5 M NaOH. The cakes were unwashed or washed with ethanol or water and were autoclaved at 121°C for 30 minutes. Alkaline hydrolysis combined with ethanol washing decreased the phorbol ester concentration in the cake by 98%. Histopathological findings included diffuse degeneration of the liver and edema around the pulmonary vessels in the nonhydrolyzed groups. In addition, nontreated females mated with males of nonhydrolyzed unwashed group showed a decreased number of live fetuses and an increased placental weight. There were no signs of toxicity in rats given hydrolyzed cakes washed and unwashed, indicating that alkaline hydrolysis associated with heat treatment is an efficient method for detoxification of the J. curcas cake.
Estimating Bus Loads and OD Flows Using Location-Stamped Farebox and Wi-Fi Signal Data
Authors: Ji Yuxiong , Zhao Jizhou , Zhang Zhiming , Du Yuchuan
Published: May 2017

Electronic fareboxes integrated with Automatic Vehicle Location (AVL) systems can provide location-stamped records to infer passenger boarding at individual stops. However, bus loads and Origin-Destination (OD) flows, which are useful for route planning, design, and real-time controls, cannot be derived directly from farebox data. Recently, Wi-Fi sensors have been used to collect passenger OD flow information. But the data are insufficient to capture the variation of passenger demand across bus trips. In this study, we propose a hierarchical Bayesian model to estimate trip-level OD flow matrices and a period-level OD flow matrix using sampled OD flow data collected by Wi-Fi sensors and boarding data provided by fareboxes. Bus loads on each bus trip are derived directly from the estimated trip-level OD flow matrices. The proposed method is evaluated empirically on an operational bus route and the results demonstrate that it provides good and detailed transit route-level passenger demand information by combining farebox and Wi-Fi signal data.
Effects of (1E,4E)-2-Methyl-1,5-bis(4-nitrophenyl)penta-1,4-dien-3-one onTrypanosoma cruziand Its Combinational Effect with Benznidazole, Ketoconazole, or Fluconazole
Authors: Peron Francieli , Lazarin-Bidóia Danielle , Ud Din Zia , Rodrigues-Filho Edson , Ueda-Nakamura Tânia , Silva Sueli de Oliveira , Nakamura Celso Vataru
Published: May 2017

This study reports the activity induced by (1E,4E)-2-methyl-1,5-bis(4-nitrophenyl)penta-1,4-dien-3-one(A3K2A3)againstTrypanosoma cruzi.This compound showed trypanocidal activity against the multiplicative epimastigote and amastigote forms of this protozoan, with IC50values of1.99±0.17and1.20±0.16 μM, respectively, and EC50value of15.57±0.34 μM against trypomastigotes. The combination ofA3K2A3with benznidazole or ketoconazole demonstrated strong synergism, increasing effectiveness against trypomastigotes or epimastigotes ofT. cruzi. In addition, the drug combination ofA3K2A3with benznidazole or ketoconazole on LLCMK2cells demonstrated an antagonist effect, which resulted in greater protection of the cells from drug damage. The combination of the compound with fluconazole was not effective. Transmission and scanning electron micrographs showed changes on parasites, mainly in the cytoplasmatic membrane, nucleus, mitochondrion, and Golgi complex, and a large increase in the number of autophagosome-like structures and lipid-storage bodies, accompanied by volume reduction and rounding of the parasite.A3K2A3might be a promising compound againstT. cruzi.
Differences in Multidisciplinary and Interdisciplinary Treatment Programs for Fibromyalgia: A Mapping Review
Authors: Giusti Emanuele Maria , Castelnuovo Gianluca , Molinari Enrico
Published: May 2017

Fibromyalgia is a multifaceted chronic pain syndrome and the integration of different health disciplines is strongly recommended for its care. The interventions based on this principle are very heterogeneous and the difference across their structures has not been extensively studied, leading to incorrect conclusions when their outcomes are pooled. The objective of this mapping review was to summarize the characteristics of these programs, with particular focus on the integration of their components. We performed a search of the literature about treatments for fibromyalgia involving multiple disciplines on PubMed and Scopus. Starting from 560 articles, we included 22 noncontrolled studies, 10 controlled studies, and 17 RCTs evaluating the effects of 38 multidisciplinary or interdisciplinary interventions. The average quality of the studies was low. Their outcomes were usually pain intensity, quality of life, and psychological variables. We created a map of the programs based on the degree of integration of the included disciplines, which ranged from a juxtaposition of few components to a complex harmonization of different perspectives obtained through teamwork strategies. The rehabilitation programs were then thoroughly described with regard to the duration, setting, therapeutic components, and professionals included. The implications for future quantitative reviews are discussed.
NGAL as an Early Predictive Marker of Diabetic Nephropathy in Children and Young Adults with Type 1 Diabetes Mellitus
Authors: Papadopoulou-Marketou Nektaria , Margeli Alexandra , Papassotiriou Ioannis , Chrousos George P. , Kanaka-Gantenbein Christina , Wahlberg Jeanette
Published: May 2017

Aims. Type 1 diabetes (T1D) is often associated with early microvascular complications. Previous studies demonstrated that increased systolic (SAP) and diastolic arterial blood pressures (DAP) are linked to microvascular morbidity in T1D. The aim of the study was to investigate the predictive role of neutrophil gelatinase-associated lipocalin (NGAL) in unravelling early cardio-renal dysfunction in T1D. Methods. Two T1D patient groups participating in two-centre prospective cohorts were studied. Group A consisted of 57 participants aged 13.9 years (SD: 3.1) and group B consisted of 59 patients aged 28.0 years (SD: 4.4). Forty-nine healthy children [age: 10.5 years (SD: 6.6)] and 18 healthy adults [age 27.7 years (SD: 4.2)] served as controls. Serum concentrations of NGAL (ELISA) were determined, and SAP and DAP were examined (SAP and DAP also expressed as z-scores in the younger group). Results. NGAL correlated positively with SAP in both patient groups (P=0.020 and P=0.031, resp.) and SAP z-score (P=0.009) (group A) and negatively with eGFR in both groups (P<0.001 and P<0.001, resp.). Conclusions. NGAL may be proposed as a biomarker of early renal dysfunction even in nonalbuminuric T1D patients, since it was strongly associated with renal function decline and increasing systolic arterial pressure even at prehypertensive range in people with T1D, in a broad age range.
Propionibacterium acnes Is an Unusual Cause of Acute Scrotal Abscess in a Preterm Infant
Authors: Nishizaki Naoto , Okazaki Tadaharu , Adachi Yu , Obinata Kaoru , Shoji Hiromichi , Shimizu Toshiaki
Published: May 2017

Acute scrotal abscess is an extremely rare condition in neonates and may mimic testicular torsion. Most of these abscesses have reportedly been due to Staphylococcus and Salmonella spp. infections. We herein report a unilateral acute scrotal abscess in a preterm infant born at 26 weeks in whom Propionibacterium acnes was isolated from the collected scrotal fluid culture. To our knowledge, this is the first case report implicating P. acnes as a causative agent of neonatal scrotal abscess. Based on such findings, P. acnes infection should be considered in differential diagnosis of acute scrotal abscess in neonates, particularly in preterm infants.
Fungal Dimorphism and Virulence: Molecular Mechanisms for Temperature Adaptation, Immune Evasion, and In Vivo Survival
Authors: Gauthier Gregory M.
Published: May 2017

The thermally dimorphic fungi are a unique group of fungi within the Ascomycota phylum that respond to shifts in temperature by converting between hyphae (22–25°C) and yeast (37°C). This morphologic switch, known as the phase transition, defines the biology and lifestyle of these fungi. The conversion to yeast within healthy and immunocompromised mammalian hosts is essential for virulence. In the yeast phase, the thermally dimorphic fungi upregulate genes involved with subverting host immune defenses. This review highlights the molecular mechanisms governing the phase transition and recent advances in how the phase transition promotes infection.
Generation of Recombinant Antibodies against the beta-(1,6)-Branched beta-(1,3)-D-Glucan Schizophyllan from Immunized Mice via Phage Display
Authors: Josewski Jörn , Buchmeier Sabine , Frenzel André , Tinnefeld Philip , Dübel Stefan , Rau Udo
Published: May 2017

beta-(1,6)-Branched beta-(1,3)-D-glucans like schizophyllan from the basidiomycete Schizophyllum commune excite various immunostimulatory effects and have been clinically tested as adjuvants. Some of the glucans are also applicable in food or petrol industry due to their viscosity and temperature stability in aqueous solution. Antibodies against these glucans could be used as tool for analysis of glucan preparations or for further research of its bioactivity. Therefore, an immune phage display library was constructed from mice immunized with schizophyllan. Three recombinant monoclonal antibodies were isolated from this library by affinity selection (panning) on schizophyllan. The half-maximal effective concentration (EC50) values for those antibodies varied between 16.4 ng mL−1 and 21.3 ng mL−1. The clones showed binding specificity not only for schizophyllan but also for other beta-(1,6)-branched beta-(1,3)-D-glucans of similar macromolecular structure. Denaturation of the secondary structure led to a reduced antibody binding, indicating an epitope requiring the correct conformation of the triple helical structure of the glucans.
Primary Renal Carcinoid with Bilateral Multiple Clear Cell Papillary Renal Cell Carcinomas
Authors: Anderson Daniel A. , Tretiakova Maria S.
Published: May 2017

Clear cell papillary renal cell carcinoma (CCPRCC) is a newly recognized entity in the 2016 WHO classification and usually presents as a small, circumscribed, solitary mass of indolent nature. CCPRCCs could seldom occur in conjunction with other synchronous or metachronous kidney tumors and even less frequently as bilateral masses. To our knowledge, multiple bilateral CCPRCCs have never been described with the existence of a synchronous well-differentiated neuroendocrine tumor of the kidney and hence reported here as a unique case. This case report highlights the importance in considering this entity and its unusual presentation in the differential diagnosis as a possible mimicker of Von Hippel-Lindau syndrome.
Akt Signaling Is Sustained by a CD44 Splice Isoform–Mediated Positive Feedback Loop
Authors: Liu Sali , Cheng Chonghui
Published: May 2017

Tumor cells nearly invariably evolve sustained PI3K/Akt signaling as an effective means to circumvent apoptosis and maintain survival. However, for those tumor cells that do not acquire PI3K/Akt mutations to achieve this end, the underlying mechanisms have remained obscure. Here, we describe the discovery of a splice isoform–dependent positive feedback loop that is essential to sustain PI3K/Akt signaling in breast cancer. Splice isoform CD44s promoted expression of the hyaluronan synthase HAS2 by activating the Akt signaling cascade. The HAS2 product hyaluronan further stimulated CD44s-mediated Akt signaling, creating a feed-forward signaling circuit that promoted tumor cell survival. Mechanistically, we identified FOXO1 as a bona fide transcriptional repressor of HAS2. Akt-mediated phosphorylation of FOXO1 relieved its suppression of HAS2 transcription, with FOXO1 phosphorylation status maintained by operation of the positive feedback loop. In clinical specimens of breast cancer, we established that the expression of CD44s and HAS2 was positively correlated. Our results establish a positive feedback mechanism that sustains PI3K/Akt signaling in tumor cells, further illuminating the nearly universal role of this pathway in cancer cell survival. Cancer Res; 77(14); 3791–801. ©2017 AACR.
MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR+/HER2− Metastatic Breast Cancer
Authors: Dickler Maura N. , Tolaney Sara M. , Rugo Hope S. , Cortés Javier , Diéras Véronique , Patt Debra , Wildiers Hans , Hudis Clifford A. , O'Shaughnessy Joyce , Zamora Esther , Yardley Denise A. , Frenzel Martin , Koustenis Andrew , Baselga José
Published: May 2017

Purpose: The phase II MONARCH 1 study was designed to evaluate the single-agent activity and adverse event (AE) profile of abemaciclib, a selective inhibitor of CDK4 and CDK6, in women with refractory hormone receptor–positive (HR+), HER2− metastatic breast cancer (MBC).

Experimental Design: MONARCH 1 was a phase II single-arm open-label study. Women with HR+/HER2− MBC who had progressed on or after prior endocrine therapy and had 1 or 2 chemotherapy regimens in the metastatic setting were eligible. Abemaciclib 200 mg was administered orally on a continuous schedule every 12 hours until disease progression or unacceptable toxicity. The primary objective of MONARCH 1 was investigator-assessed objective response rate (ORR). Other endpoints included clinical benefit rate, progression-free survival (PFS), and overall survival (OS).

Results: Patients (n = 132) had a median of 3 (range, 1–8) lines of prior systemic therapy in the metastatic setting, 90.2% had visceral disease, and 50.8% had ≥3 metastatic sites. At the 12-month final analysis, the primary objective of confirmed objective response rate was 19.7% (95% CI, 13.3–27.5; 15% not excluded); clinical benefit rate (CR+PR+SD≥6 months) was 42.4%, median progression-free survival was 6.0 months, and median overall survival was 17.7 months. The most common treatment-emergent AEs of any grade were diarrhea, fatigue, and nausea; discontinuations due to AEs were infrequent (7.6%).

Conclusions: In this poor-prognosis, heavily pretreated population with refractory HR+/HER2− metastatic breast cancer, continuous dosing of single-agent abemaciciclib was well tolerated and exhibited promising clinical activity. Clin Cancer Res; 23(17); 5218–24. ©2017 AACR.
Metformin Synergizes with BCL-XL/BCL-2 Inhibitor ABT-263 to Induce Apoptosis Specifically in p53-Defective Cancer Cells
Authors: Li Xinzhe , Li Bo , Ni Zhenhong , Zhou Peng , Wang Bin , He Jintao , Xiong Haojun , Yang Fan , Wu Yaran , Lyu Xilin , Zhang Yan , Zeng Yijun , Lian Jiqin , He Fengtian
Published: May 2017

p53 deficiency, a frequent event in multiple kinds of malignancies, decreases the sensitivity of diverse targeted chemotherapeutics including the BCL-XL/BCL-2 inhibitor ABT-263. Loss of p53 function can activate mTOR complex 1 (mTORC1), which may make it a vulnerable target. Metformin has shown anti-neoplastic efficiency partially through suppressing mTORC1. However, it remains unknown whether mTORC1 activation confers ABT-263 resistance and whether metformin can overcome it in the p53-defective contexts. In this study, we for the first time demonstrated that metformin and ABT-263 synergistically elicited remarkable apoptosis through orchestrating the proapoptotic machineries in various p53-defective cancer cells. Mechanistic studies revealed that metformin sensitized ABT-263 via attenuating mTORC1-mediated cap-dependent translation of MCL-1 and survivin and weakening internal ribosome entry site (IRES)-dependent translation of XIAP. Meanwhile, ABT-263 sensitized metformin through disrupting the BCL-XL/BIM complex. However, metformin and ABT-263 had no synergistic killing effect in p53 wild-type (p53-WT) cancer cells because the cotreatment dramatically induced the senescence-associated secretory phenotype (SASP) in the presence of wild type p53, and SASP could aberrantly activate the AKT/ERK–mTORC1–4EBP1–MCL-1/survivin signaling axis. Blocking the axis using corresponding kinase inhibitors or neutralizing antibodies against different SASP components sensitized the cotreatment effect of metformin and ABT-263 in p53-WT cancer cells. The in vivo experiments showed that metformin and ABT-263 synergistically inhibited the growth of p53-defective (but not p53-WT) cancer cells in tumor xenograft nude mice. These results suggest that the combination of metformin and ABT-263 may be a novel targeted therapeutic strategy for p53-defective cancers. Mol Cancer Ther; 16(9); 1806–18. ©2017 AACR.
Enzymatic Inactivation of Endogenous IgG by IdeS Enhances Therapeutic Antibody Efficacy
Authors: Järnum Sofia , Runström Anna , Bockermann Robert , Winstedt Lena , Crispin Max , Kjellman Christian
Published: May 2017

Endogenous plasma IgG sets an immunologic threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation of cellular antibody receptors by endogenous antibody limits antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Here, we show how enzymatic cleavage of IgG using the bacterial enzyme IdeS can be utilized to empty both high and low affinity Fcγ-receptors and clear the entire endogenous antibody pool. Using in vitro models, tumor animal models as well as ex vivo analysis of sera collected during a previous clinical trial with IdeS, we show how clearing of competing plasma antibody levels with IdeS unblocks cellular antibody receptors. We show that therapeutic antibodies against breast cancer (trastuzumab), colon cancer (cetuximab), and lymphomas (rituximab and alemtuzumab) can be potentiated when endogenous IgG is removed. Overall, IdeS is shown to be a potent tool to reboot the human antibody repertoire and to generate a window to preferentially load therapeutic antibodies onto effector cells and thereby create an armada of dedicated tumor-seeking immune cells. Mol Cancer Ther; 16(9); 1887–97. ©2017 AACR.