bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with a bad functional prognosis in early inflammatory back pain: results from the DESIR cohort
Authors: Lukas C , Dougados M , Combe B
Published: February 2016

Background

Spondyloarthritis (SpA) is a heterogeneous disease with hardly predictable potential courses. We aimed at determining prognostic factors of bad functional outcome at 2 years in patients with early inflammatory back pain (IBP).

Methods

Data from patients included in the French multicentre devenir des spondylarthropathies indifférenciées récentes (DESIR) cohort, that is, suffering from IBP starting before 50 years of age and lasting for 3–36 months, were used. A bad functional outcome at 24 months was defined as an increase in bath ankylosing spondylitis functional index (BASFI), or BASFI at 2 years higher than the 75th centile in the cohort. Demographic, clinical, biological and radiological data collected at inclusion were compared in patients with bad functional outcome versus others, by χ2test, then by a multivariate logistic regression model with stepwise selection of relevant factors.

Results

513 patients (54.4% females, 72.2% fulfilling ASAS criteria) were assessed. Of those, 130 (25.3%) fulfilled the aforementioned criteria of a bad functional outcome (BASFI increase ≥4 units or ≥36 at 2 years). Multivariate analysis revealed that not fulfilling ASAS criteria, female sex, age >33 years, lower educational level, active smoking status and high disease activity according to bath ankylosing spondylitis disease activity index (BASDAI) at baseline were independently associated with a bad functional outcome at 24 months. Sensitivity analyses restricted to patients fulfilling ASAS criteria for SpA resulted in similar results.

Conclusion

We observed, in a large prospective cohort of patients with early IBP, formerly described bad prognostic factors, especially a low educational level, an older age and a high disease activity at onset, and revealed that active smoking status and female sex were also independently associated with a poor outcome. Fulfilment of ASAS criteria, on the other hand, was predictive of a better outcome, most likely due to the more consensual management of a defined disease.
The use of nutritional supplements in dressage and eventing horses
Authors: Agar C. , Gemmill R. , Hollands T. , Freeman S. L.
Published: February 2016

The aim of the study was to determine which types of nutritional supplements were used in dressage and eventing horses, and the reasons that owners used supplements. An online questionnaire was distributed through British Eventing and Dressage websites, to collect data on demographics of owners and their horses, supplements used and their opinion on health and performance problems. Data were evaluated using descriptive analysis, Sign and Fisher's exact tests for quantitative data, and categorisation of qualitative data. In total, 599 responses met the inclusion criteria (441 dressage and 158 eventing horse owners). Participants had 26.4 (3–60) (mean (range)) years of riding experience, owned 1.2 (0–10) horses and used 2 (0–12) supplements in their highest performing horse. The main health and performance issues identified for dressage were ‘energy/behaviour’, ‘lameness’ and ‘back and muscle problems’. The main issues for eventing were ‘stamina and fitness levels’,’ lameness’ and ‘energy/behaviour’. The main reasons for using supplements in their highest performing horse were ‘joints and mobility’, and ‘behaviour’ for dressage, and ‘electrolytes’, and ‘joints and mobility’ for eventing. Lameness and behavioural problems were significant concerns within both disciplines. There was incongruence between owners’ opinions of problems within their discipline and their reasons for using supplements.
What is the veterinary professional identity? Preliminary findings from web‐based continuing professional development in veterinary professionalism
Authors: Armitage‐Chan E. , Maddison J. , May S. A.
Published: February 2016

Professionalism and professional skills are increasingly being incorporated into veterinary curricula; however, lack of clarity in defining veterinary professionalism presents a potential challenge for directing course outcomes that are of benefit to the veterinary professional. An online continuing education course in veterinary professionalism was designed to address a deficit in postgraduate support in this area; as part of this course, delegates of varying practice backgrounds participated in online discussions reflecting on the implications of professional skills for their clinical practice. The discussions surrounding the role of the veterinary professional and reflecting on strengths and weaknesses in professional skills were analysed using narrative methodology, which provided an understanding of the defining skills and attributes of the veterinary professional, from the perspectives of those involved (i.e. how vets understood their own career identity). The veterinary surgeon was understood to be an interprofessional team member, who makes clinical decisions in the face of competing stakeholder needs and works in a complex environment comprising multiple and diverse challenges (stress, high emotions, financial issues, work–life balance). It was identified that strategies for accepting fallibility, and those necessary for establishing reasonable expectations of professional behaviour and clinical ability, are poorly developed.
Taurine supplementation attenuates delayed increase in exercise-induced arterial stiffness
Authors: Ra Song-Gyu , Choi Youngju , Akazawa Nobuhiko , Ohmori Hajime , Maeda Seiji
Published: February 2016

There is a delayed increase in arterial stiffness after eccentric exercise that is possibly mediated by the concurrent delayed increase in circulating oxidative stress. Taurine has anti-oxidant action, and taurine supplementation may be able to attenuate the increase in oxidative stress after exercise. The purpose of the present study was to investigate whether taurine supplementation attenuates the delayed increase in arterial stiffness after eccentric exercise. In the present double-blind, randomized, and placebo-controlled trial, we divided 29 young, healthy men into 2 groups. Subjects received either 2.0 g of placebo (n = 14) or taurine (n = 15) 3 times per day for 14 days prior to the exercise, on the day of exercise, and the following 3 days. The exercise consisted of 2 sets of 20 maximal-effort eccentric repetitions with the nondominant arm only. On the morning of exercise and for 4 days thereafter, we measured serum malondialdehyde (MDA) and carotid–femoral pulse wave velocity (cfPWV) as indices of oxidative stress and arterial stiffness, respectively. On the third and fourth days after exercise, both MDA and cfPWV significantly increased in the placebo group. However, these elevations were significantly attenuated in the taurine group. The increase in MDA was associated with an increase in cfPWV from before exercise to 4 days after exercise (r = 0.597, p < 0.05) in the placebo group, but not in the taurine group. Our results suggest that delayed increase in arterial stiffness after eccentric exercise was probably affected by the exercise-induced oxidative stress and was attenuated by the taurine supplementation.
Morphological and histochemical characterization of the secretory sites of bioactive compounds in leaves of Lantana camara L. (Verbenaceae)
Authors: Silva Stefany Cristina de Melo , Tozin Luiz Ricardo dos Santos , Rodrigues Tatiane Maria
Published: February 2016

Lantana camara L. is a species of Verbenaceae known for its aromatic and medicinal properties. Compounds extracted from its leaves are used to treat infections of the respiratory tract and have demonstrated antimicrobial potential and repellent action to Aedes mosquitoes. Our aim was to identify and characterize the main production sites of the biologically active substances in the leaf blades of L. camara. Leaf samples were collected from plants living in the Brazilian Cerrado and processed according to standard techniques in plant anatomy and histochemistry as well as scanning and transmission electron microscopy. Six morphotypes of glandular trichomes (I–VI) were identified; they differ in shape and size, number of constituent cells, subcellular aspects, and form of accumulation, as well as release and composition of the secretion. Idioblasts producing hydrophilic and lipophilic substances were observed in the mesophyll and may be associated with protection of the plant against herbivores and pathogens and maintenance of the water potential of leaf tissues, complementing the action of glandular trichomes. Our results contribute to the understanding and knowledge of the sites responsible for the production of substances with ecological and medicinal value in Verbenaceae species, and may provide a foundation for future studies in different areas of science focusing on the manipulation of this production.
Extension and validation of the GLYCAM force field parameters for modeling glycosaminoglycans
Authors: Singh Arunima , Tessier Matthew B. , Pederson Kari , Wang Xiaocong , Venot Andre P. , Boons Geert-Jan , Prestegard James H. , Woods Robert J.
Published: February 2016

Glycosaminoglycans (GAGs) are an important class of carbohydrates that serve critical roles in blood clotting, tissue repair, cell migration and adhesion, and lubrication. The variable sulfation pattern and iduronate ring conformations in GAGs influence their polymeric structure and nature of interaction. This study characterizes several heparin-like GAG disaccharides and tetrasaccharides using NMR and molecular dynamics simulations to assist in the development of parameters for GAGs within the GLYCAM06 force field. The force field additions include parameters and charges for a transferable sulfate group for O- and N-sulfation, neutral (COOH) forms of iduronic and glucuronic acid, and Δ4,5-unsaturated uronate (ΔUA) residues. ΔUA residues frequently arise from the enzymatic digestion of heparin and heparin sulfate. Simulations of disaccharides containing ΔUA reveal that the presence of sulfation on this residue alters the relative populations of 1H2 and 2H1 ring conformations. Simulations of heparin tetrasaccharides containing N-sulfation in place of N-acetylation on glucosamine residues influence the ring conformations of adjacent iduronate residues.
Enhancement of fengycin production in Bacillus amyloliquefaciens by genome shuffling and relative gene expression analysis using RT-PCR
Authors: Zhao Junfeng , Zhang Chong , Lu Jing , Lu Zhaoxin
Published: February 2016

Genome shuffling is an efficient approach for the rapid engineering of microbial strains with desirable industrial phenotypes. In this study, we used genome shuffling in an attempt to improve fengycin production of the wild-type strain Bacillus amyloliquefaciens ES-2-4. After 2 rounds of genome shuffling, a high-yield recombinant F2-72 (FMB72) strain that exhibited 8.30-fold increases in fengycin production was obtained. Comparative analysis of synthetase gene (fenA) expression was conducted between the initial and shuffled strains using fluorescent quantitation RT-PCR. Delta CT (threshold cycle) relative quantitation analysis revealed that fengycin synthetase gene (fenA) expression at the transcriptional level in the FMB72 strain was 12.77-fold greater than in the ES-2-4 wild type. The shuffled strain has a potential application in food and pharmaceutical industries. At the same time, the analysis of improved phenotypes will provide more valuable data for inverse metabolic engineering.
The elastic wave motions for a photothermal medium of a dual-phase-lag model with an internal heat source and gravitational field
Authors: Lotfy Kh.
Published: February 2016

In this work, the dual-phase-lag (DPL) heat transfer model is introduced to study the problem of an isotropic generalized thermoelastic medium with an internal heat source that is moving with a constant speed. Thermal loading at the free surface of a semi-infinite semiconconducting medium coupled plasma waves with the effect of mechanical force during a photothermal process to study the effect of a gravity field. Harmonic wave analysis is used to obtain exact expressions for the considered variables, also the carrier density coefficients were obtained analytically. The variations of the considered variables through the horizontal distance are illustrated graphically under the effects of several parameters based on the DPL model. The results are discussed and depicted graphically.
The social, economic, and environmental importance of inland fish and fisheries
Authors: Lynch Abigail J. , Cooke Steven J. , Deines Andrew M. , Bower Shannon D. , Bunnell David B. , Cowx Ian G. , Nguyen Vivian M. , Nohner Joel , Phouthavong Kaviphone , Riley Betsy , Rogers Mark W. , Taylor William W. , Woelmer Whitney , Youn So-Jung , Beard T. Douglas
Published: February 2016

Though reported capture fisheries are dominated by marine production, inland fish and fisheries make substantial contributions to meeting the challenges faced by individuals, society, and the environment in a changing global landscape. Inland capture fisheries and aquaculture contribute over 40% to the world’s reported finfish production from less than 0.01% of the total volume of water on earth. These fisheries provide food for billions and livelihoods for millions of people worldwide. Herein, using supporting evidence from the literature, we review 10 reasons why inland fish and fisheries are important to the individual (food security, economic security, empowerment), to society (cultural services, recreational services, human health and well-being, knowledge transfer and capacity building), and to the environment (ecosystem function and biodiversity, as aquatic “canaries”, the “green food” movement). However, the current limitations to valuing the services provided by inland fish and fisheries make comparison with other water resource users extremely difficult. This list can serve to demonstrate the importance of inland fish and fisheries, a necessary first step to better incorporating them into agriculture, land-use, and water resource planning, where they are currently often underappreciated or ignored.
Regional scale hydrogeochemical mapping of the northern Yilgarn Craton, Western Australia: a new technology for exploration in arid Australia
Authors: Gray David J. , Noble Ryan R.P. , Reid Nathan , Sutton Gordon J. , Pirlo Mark C.
Published: February 2016

The northern Yilgarn Craton, with an extensive mineral exploration history and relatively fresh and neutral groundwaters, was selected to test the utility of regional hydrogeochemical mapping in Australia. The assembled data of 2509 groundwater samples (generally at 4–8 km spacing) are relatively unbiased, allowing robust statistical analysis such as testing sample types (flowing v. ‘stagnant’), contamination, and lithological controls on groundwater characteristics. Lithological indicators were developed to map underlying bedrock through cover. Areas with discrepancies between groundwater results and previous geological mapping were identified. Where these are areas previously discounted as prospective for mineral commodities, they may now be re-considered on this basis. Even in well explored parts of this region, this study identified new areas which may have prospective rocks overlain with a thin (<50 m) veneer of granitic material. A large background data set was produced that has significant benefits for lithological discrimination, mineral exploration, guiding human and livestock drinking water supplies and environmental management (e.g. mine closure).

Groundwater chemistry can effectively map large-scale lithological changes in these semi-arid environments, and in turn can reduce uncertainly about the prospectivity of areas within the northern Yilgarn Craton. This should reduce the drilling and associated costs required to delineate a target. The methods and interpretation developed in this study will enhance mineral exploration into covered environments as much of the northern two thirds of Australia has similar groundwater environments. This methodology can be expanded into covered arid terrains worldwide. Additionally, this can be used as background to improve interpretation of other small scale studies. Improving the exploration potential of other more difficult regions of Australia will encourage industry exploration in Australia, and provide potential future economic gains.
Fatty Acids Analysis, Antioxidant and Biological Activity of Fixed Oil ofAnnona muricataL. Seeds
Authors: Elagbar Zaha A. , Naik Rajashri R. , Shakya Ashok K. , Bardaweel Sanaa K.
Published: February 2016

The total oil yield and the fatty acid composition were determined in theAnnona muricataL. fixed oil using organic solvent extraction and GC-FID. The seeds were found to contain about ~21.5% of crude fixed oil on a dry weight basis. The crude oil containing fatty acid was converted into methyl esters and analysed by GC-FID. Fourteen fatty acids were identified using GC-FID. The major monounsaturated and saturated fatty acids were oleic acid (39.2%) and palmitic acid (19.1–19.2%), respectively, whereas theα-linolenic acid (1.2%) and linoleic acid (34.9%) were polyunsaturated fatty acid. The other saturated acids were stearic acid (3.3%), arachidic acid (0.4%), myristic acid (0.1%), heptadecanoic acid (0.1%), behenic acid (0.1%), and lignoceric acid (0.1%). Some of the fatty acids have not been reported earlier from the oil ofAnnona muricataL. Fixed oil exhibited significant free radical scavenging activity which was measured using DPPH and is also known to inhibit the gastrointestinal motility significantly.
Cubic Trigonometric Nonuniform Spline Curves and Surfaces
Authors: Yan Lanlan
Published: February 2016

A class of cubic trigonometric nonuniform spline basis functions with a local shape parameter is constructed. Their totally positive property is proved. The associated spline curves inherit most properties of usual polynomialB-spline curves and enjoy some other advantageous properties for engineering design. They haveC2continuity at single knots. For equidistant knots, they haveC3continuity andC5continuity for particular choice of shape parameter. They can express freeform curves as well as ellipses. The associated spline surfaces can exactly represent the surfaces of revolution. Thus the curve and surface representation scheme unifies the representation of freeform shape and some analytical shapes, which is popular in engineering.
Energy Modulated Photon Radiotherapy: A Monte Carlo Feasibility Study
Authors: Zhang Ying , Feng Yuanming , Ming Xin , Deng Jun
Published: February 2016

A novel treatment modality termed energy modulated photon radiotherapy (EMXRT) was investigated. The first step of EMXRT was to determine beam energy for each gantry angle/anatomy configuration from a pool of photon energy beams (2 to 10 MV) with a newly developed energy selector. An inverse planning system using gradient search algorithm was then employed to optimize photon beam intensity of various beam energies based on presimulated Monte Carlo pencil beam dose distributions in patient anatomy. Finally, 3D dose distributions in six patients of different tumor sites were simulated with Monte Carlo method and compared between EMXRT plans and clinical IMRT plans. Compared to current IMRT technique, the proposed EMXRT method could offer a better paradigm for the radiotherapy of lung cancers and pediatric brain tumors in terms of normal tissue sparing and integral dose. For prostate, head and neck, spine, and thyroid lesions, the EMXRT plans were generally comparable to the IMRT plans. Our feasibility study indicated that lower energy (<6 MV) photon beams could be considered in modern radiotherapy treatment planning to achieve a more personalized care for individual patient with dosimetric gains.
Rapid and Efficient Synthesis ofω-Alkylenediphosphoric Acids from Phosphorus Oxychloride
Authors: Meziane Dalila , Elias Abdelhamid , Guénin Erwann
Published: February 2016

The aim of this investigation was to develop an efficient, rapid, and selective method for the synthesis ofω-alkylenediphosphoric acids (HO)2(O)P-O-CH2n-O-P(O)(OH)2from reaction of several diols with phosphorus oxychloride. The reaction was investigated using three methodologies: (i) presence of a base, (ii) classical heating, and (iii) use of microwave irradiation. Influence of reaction temperature and molar ratio of reagents, as well as the nature of the solvent, was studied using these three different methods.
Description of the Magnetic Field and Divergence of Multisolenoid Aharonov-Bohm Potential
Authors: Aliev Araz R. , Eyvazov Elshad H. , Ibrahim Said F. M. , Zedan Hassan A.
Published: February 2016

Explicit formulas for the magnetic field and divergence of multisolenoid Aharonov-Bohm potential are obtained; the mathematical essence of this potential is explained. It is shown that the magnetic field and divergence of this potential are very singular generalized functions concentrated at a finite number of thin solenoids. Deficiency index is found for the minimal operator generated by the Aharonov-Bohm differential expression.
Effects of Duct Cross Section Camber and Thickness on the Performance of Ducted Propulsion Systems for Aeronautical Applications
Authors: Bontempo Rodolfo , Manna Marcello
Published: February 2016

The axisymmetric flow field around a ducted rotor is thoroughly analysed by means of a nonlinear and semi-analytical model which is able to deal with some crucial aspects of shrouded systems like the interaction between the rotor and the duct, and the slipstream contraction and rotation. Not disregarding the more advanced CFD based methods, the proposed procedure is characterised by a very low computational cost that makes it very appealing as analysis tool in the preliminary steps of a design procedure of hierarchical type. The work focuses on the analysis of the effects of the camber and thickness of the duct cross section onto the performance of the device. It has been found that an augmentation of both camber and thickness of the duct leads to an increase of the propulsive ideal efficiency.
Fault Diagnosis of Rotating Machinery Based on Adaptive Stochastic Resonance and AMD-EEMD
Authors: Shi Peiming , Su Cuijiao , Han Dongying
Published: February 2016

An adaptive stochastic resonance and analytical mode decomposition-ensemble empirical mode decomposition (AMD-EEMD) method is proposed for fault diagnosis of rotating machinery in this paper. Firstly, the stochastic resonance system is optimized by particle swarm optimization (PSO), and the best structure parameters are obtained. Then, the signal with noise is put into the stochastic resonance system and denoising and enhancing the signal. Secondly, the signal output from the stochastic resonance system is extracted by analytical mode decomposition (AMD) method. Finally, the signal is decomposed by ensemble empirical mode decomposition (EEMD) method. The simulation results show that the optimal stochastic resonance system can effectively improve the signal-to-noise ratio, and the number of effective components of EEMD decomposition is significantly reduced after using AMD, thus improving the decomposition results of EEMD and enhancing the amplitude of components frequency. Through the extraction of the rolling bearing fault signal feature proved that the method has a good effect.
A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver
Authors: Im Hwi-Jin , Kim Hyeong-Geug , Lee Jin-Seok , Kim Hyo-Seon , Cho Jung-Hyo , Jo Il-Joo , Park Sung-Joo , Son Chang-Gue
Published: February 2016

Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8+ T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698–704. ©2016 AACR.
Distinct Subtypes of Gastric Cancer Defined by Molecular Characterization Include Novel Mutational Signatures with Prognostic Capability
Authors: Li Xiangchun , Wu William K.K. , Xing Rui , Wong Sunny H. , Liu Yuexin , Fang Xiaodong , Zhang Yanlin , Wang Mengyao , Wang Jiaqian , Li Lin , Zhou Yong , Tang Senwei , Peng Shaoliang , Qiu Kunlong , Chen Longyun , Chen Kexin , Yang Huanming , Zhang Wei , Chan Matthew T.V. , Lu Youyong , Sung Joseph J.Y. , Yu Jun
Published: February 2016

Gastric cancer is not a single disease, and its subtype classification is still evolving. Next-generation sequencing studies have identified novel genetic drivers of gastric cancer, but their use as molecular classifiers or prognostic markers of disease outcome has yet to be established. In this study, we integrated somatic mutational profiles and clinicopathologic information from 544 gastric cancer patients from previous genomic studies to identify significantly mutated genes (SMG) with prognostic relevance. Gastric cancer patients were classified into regular (86.8%) and hypermutated (13.2%) subtypes based on mutation burden. Notably, TpCpW mutations occurred significantly more frequently in regular, but not hypermutated, gastric cancers, where they were associated with APOBEC expression. In the former group, six previously unreported (XIRP2, NBEA, COL14A1, CNBD1, ITGAV, and AKAP6) and 12 recurrent mutated genes exhibited high mutation prevalence (≥3.0%) and an unexpectedly higher incidence of nonsynonymous mutations. We also identified two molecular subtypes of regular-mutated gastric cancer that were associated with distinct prognostic outcomes, independently of disease staging, as confirmed in a distinct patient cohort by targeted capture sequencing. Finally, in diffuse-type gastric cancer, CDH1 mutation was found to be associated with shortened patient survival, independently of disease staging. Overall, our work identified previously unreported SMGs and a mutation signature predictive of patient survival in newly classified subtypes of gastric cancer, offering opportunities to stratify patients into optimal treatment plans based on molecular subtyping. Cancer Res; 76(7); 1724–32. ©2016 AACR.
HDAC Inhibition Induces MicroRNA-182, which Targets RAD51 and Impairs HR Repair to Sensitize Cells to Sapacitabine in Acute Myelogenous Leukemia
Authors: Lai Tsung-Huei , Ewald Brett , Zecevic Alma , Liu Chaomei , Sulda Melanie , Papaioannou Dimitrios , Garzon Ramiro , Blachly James S. , Plunkett William , Sampath Deepa
Published: February 2016

Purpose: The double-strand breaks elicited by sapacitabine, a clinically active nucleoside analogue prodrug, are repaired by RAD51 and the homologous recombination repair (HR) pathway, which could potentially limit its toxicity. We investigated the mechanism by which histone deacetylase (HDAC) inhibitors targeted RAD51 and HR to sensitize acute myelogenous leukemia (AML) cells to sapacitabine.

Experimental Design: Chromatin immunoprecipitation identified the role of HDACs in silencing miR-182 in AML. Immunoblotting, gene expression, overexpression, or inhibition of miR-182 and luciferase assays established that miR-182 directly targeted RAD51. HR reporter assays, apoptotic assays, and colony-forming assays established that the miR-182, as well as the HDAC inhibition–mediated decreases in RAD51 inhibited HR repair and sensitized cells to sapacitabine.

Results: The gene repressors, HDAC1 and HDAC2, became recruited to the promoter of miR-182 to silence its expression in AML. HDAC inhibition induced miR-182 in AML cell lines and primary AML blasts. miR-182 targeted RAD51 protein both in luciferase assays and in AML cells. Overexpression of miR-182, as well as HDAC inhibition–mediated induction of miR-182 were linked to time- and dose-dependent decreases in the levels of RAD51, an inhibition of HR, increased levels of residual damage, and decreased survival after exposure to double-strand damage-inducing agents.

Conclusions: Our findings define the mechanism by which HDAC inhibition induces miR-182 to target RAD51 and highlights a novel pharmacologic strategy that compromises the ability of AML cells to conduct HR, thereby sensitizing AML cells to DNA-damaging agents that activate HR as a repair and potential resistance mechanism. Clin Cancer Res; 22(14); 3537–49. ©2016 AACR.
Integrative Genomic Analyses Yield Cell-Cycle Regulatory Programs with Prognostic Value
Authors: Cheng Chao , Lou Shaoke , Andrews Erik H. , Ung Matthew H. , Varn Frederick S.
Published: February 2016

Liposarcoma is the second most common form of sarcoma, which has been categorized into four molecular subtypes, which are associated with differential prognosis of patients. However, the transcriptional regulatory programs associated with distinct histologic and molecular subtypes of liposarcoma have not been investigated. This study uses integrative analyses to systematically define the transcriptional regulatory programs associated with liposarcoma. Likewise, computational methods are used to identify regulatory programs associated with different liposarcoma subtypes, as well as programs that are predictive of prognosis. Further analysis of curated gene sets was used to identify prognostic gene signatures. The integration of data from a variety of sources, including gene expression profiles, transcription factor–binding data from ChIP-Seq experiments, curated gene sets, and clinical information of patients, indicated discrete regulatory programs (e.g., controlled by E2F1 and E2F4), with significantly different regulatory activity in one or multiple subtypes of liposarcoma with respect to normal adipose tissue. These programs were also shown to be prognostic, wherein liposarcoma patients with higher E2F4 or E2F1 activity associated with unfavorable prognosis. A total of 259 gene sets were significantly associated with patient survival in liposarcoma, among which >50% are involved in cell cycle and proliferation.

Implications: These integrative analyses provide a general framework that can be applied to investigate the mechanism and predict prognosis of different cancer types. Mol Cancer Res; 14(4); 332–43. ©2016 AACR.
Gender Differences in Verbal and Visuospatial Working Memory Performance and Networks
Authors: Zilles David , Lewandowski Mirjana , Vieker Henning , Henseler Ilona , Diekhof Esther , Melcher Tobias , Keil Maria , Gruber Oliver
Published: February 2016

Background: Working memory (WM) has been a matter of intensive basic and clinical research for some decades now. The investigation of WM function and dysfunction may facilitate the understanding of both physiological and pathological processes in the human brain. Though WM paradigms are widely used in neuroscientific and psychiatric research, conclusive knowledge about potential moderating variables such as gender is still missing. Methods: We used functional magnetic resonance imaging to investigate the effects of gender on verbal and visuospatial WM maintenance tasks in a large and homogeneous sample of young healthy subjects. Results: We found significant gender effects on both the behavioral and neurofunctional level. Females exhibited disadvantages with a small effect size in both WM domains accompanied by stronger activations in a set of brain regions (including bilateral substantia nigra/ventral tegmental area and right Broca's area) independent of WM modality. As load and task difficulty effects have been shown for some of these regions, the stronger activations may reflect a slightly lower capacity of both WM domains in females. Males showed stronger bilateral intraparietal activations next to the precuneus which were specific for the visuospatial WM task. Activity in this specific region may be associated with visuospatial short-term memory capacity. Conclusion: These findings provide evidence for a slightly lower capacity in both WM modalities in females.
Binasal Prong versus Nasal Mask for Applying CPAP to Preterm Infants: A Randomized Controlled Trial
Authors: Say Birgul , Kanmaz Kutman Hayriye Gozde , Oguz Serife Suna , Oncel Mehmet Yekta , Arayici Sema , Canpolat Fuat Emre , Uras Nurdan , Karahan Sevilay
Published: February 2016

Background: Nasal continuous positive airway pressure (NCPAP) is being widely used for the treatment of respiratory distress syndrome (RDS) in preterm infants. However, there are only a few studies which compare different interfaces of NCPAP delivery and their effects on respiratory outcomes. Objective: We aimed to determine whether NCPAP applied with binasal prongs compared to that with a nasal mask (NM) reduces the rate of moderate/severe bronchopulmonary dysplasia (BPD) in preterm infants. Methods: Infants between 26 and 32 weeks' gestation who suffered from RDS and were treated with NCPAP were assessed. Parallel randomization was performed to eligible infants to receive NCPAP either via binasal prongs or NM. Infants were intubated if they fulfilled the predefined failure criteria. Data were collected by using the intention-to-treat principle. Results: One hundred and sixty infants were screened and 149 were randomized. Seventy-five infants in the binasal prong (NP) group and 74 in the NM group were analyzed. Mean gestational ages were 29.3 ± 1.6 vs. 29.1 ± 2.0 weeks (p = 0.55), and birth weights were 1,225 ± 257 vs. 1,282 ± 312 g (p = 0.22) in the NP and NM groups, respectively. The frequency of NCPAP failure within 24 h of life was higher in the NP than the NM group (8 vs. 0%; p = 0.09). The median duration of NCPAP was significantly higher in the NP group [median 4 (1-5) vs. 2 (1-3) h, p < 0.01]. The rate of moderate and severe BPD was significantly lower in the NM (n = 2, 2.7%) when compared with the NP group (n = 11, 14.6%; p < 0.01). The BPD/death rates were not different between the 2 groups (NM group: n = 18 or 24.3%; NP group: n = 19 or 25.3%; p = 0.51). Conclusions: The NM was successfully used for delivering NCPAP in preterm infants, and no NCPAP failure was observed within the first 24 h. These data show that applying NCPAP by NM yielded a shorter duration of NCPAP and statistically reduced the rates of moderate and severe BPD.
Stromal Cell-Derived Factor-1-3′A Polymorphism Favors HIV-1 Infection in Mexican Women
Authors: Velarde-Félix Jesús Salvador , Cázarez-Salazar Silvestre Guadalupe , Díaz-Camacho Sylvia Páz , Osuna-Ramírez Ignacio , Ochoa-Ramírez Luis Antonio , Sánchez-Zazueta Jorge Guillermo , Ramírez Martín
Published: February 2016

Objective: To evaluate the association of the stromal cell-derived factor-1 (SDF1)-3′A polymorphism to HIV-1 infection, CD4+ T-lymphocyte counts, and viral load levels in a northwestern Mexican population. Methods: We investigated allele and genotype frequencies of the SDF1-3′A polymorphism in 634 mestizo individuals from Northwest Mexico (204 HIV-1 infected persons, 256 uninfected blood donors, and 174 uninfected female sex workers) by the PCR- RFLP method and compared them using a χ2 test. We also searched for correlations between the polymorphism and CD4+ T lymphocyte and viral load counts. Results: No differences were observed in the frequencies of alleles and genotypes between patients and controls. However, in female patients we found a significantly increased prevalence of both the A allele and GA heterozygous genotype compared to male patients, female blood donors, and female sex workers. Conclusion: Here we describe the association of the SDF1-3′A polymorphism with HIV-1 infection only in women, but not to CD4+ T-lymphocyte categories, viral load levels in patients with HIV-1/AIDS, or to exposure levels in female sex workers.
Anti-HER2 Therapy Beyond Second-Line for HER2- Positive Metastatic Breast Cancer: A Short Review and Recommendations for Several Clinical Scenarios from a Spanish Expert Panel
Authors: Martínez-Jañez Noelia , Chacón Ignacio , de Juan Ana , Cruz-Merino Luis , del Barco Sònia , Fernández Isaura , García-Teijido Paula , Gómez-Bernal Amalia , Plazaola Arrate , Ponce José , Servitja Sonia , Zamora Pilar
Published: February 2016

Background: The aim of this project was to provide an expert opinion regarding anti-human epidermal growth factor receptor 2 (HER2) therapy beyond second-line treatment of metastatic breast cancer (mBC). Methods: A group of experts discussed specific issues concerning anti-HER2 therapy in late-line settings in mBC. Results: Trastuzumab emtansine (T-DM1) or dual HER2 blockade appeared to be good options for HER2-positive mBC after ≥ 2 HER2-targeted therapies. Once an objective response has been achieved with anti-HER2-containing therapy, the anti-HER2 agent can be continued until progression of the disease, unacceptable toxicity or patient decision. mBC treated with ≥ 3 consecutive lines of anti-HER therapy, ≥ 1 being a dual HER2 blockade and with early progression of disease during a fourth or later-line treatment, are clinically resistant to anti-HER therapy. For progression of metastasis in the brain after anti-HER2 therapy, lapatinib and chemotherapy appear to be a good alternative after best local treatment. Conclusions: Further clinical trials are needed to provide valuable knowledge about the best treatment options in the later settings of mBC.
Hygiene: The Looming Achilles Heel in Endoscopy
Authors: Jung Michael , Beilenhoff Ulrike
Published: February 2016

Background: Since the late 1970s there have been sporadic reports of nosocomial infections linked to endoscopic procedures. Infections by multidrug-resistant organisms (MDRO) have an increasing impact on healthcare systems worldwide. Since 2010 outbreaks involving MDRO have been reported as a result of endoscopic retrograde cholangiopancreatography (ERCP) from the USA, France, Germany and the Netherlands. Methods: This article evaluates the recent outbreaks and developments and demonstrates a structural approach to how to prevent future infections. Current national and international guidelines were used as a basis for discussions. Results: In some cases insufficient cleaning or drying supported the outbreak. In the majority of cases, outbreaks occurred despite the apparently appropriate reprocessing protocols being in use. Microlesions were identified on a number of endoscopes, which supported the growth of bacteria and represented a vehicle for the transmission of infectious material. National official bodies responded with warnings. Manufacturers informed their customers accordingly. Separate, purpose-designed reprocessing rooms and a sufficient number of competent staff provide the structural quality for a safe reprocessing. The process quality includes a thorough cleaning of all endoscope channels and crucial instrument components, followed by an automated and validated reprocessing procedure. Strict adherence to manufacturers' recommendations is essential. The outcome quality should be evaluated by regular audits, validation of reprocessing procedures and microbiological surveillance. If outbreaks occur, a close co-operation with official bodies and manufacturers is essential. Conclusion: Health care professionals and manufacturers should be aware of their responsibility to ensure patient safety. A structural approach is key in prevention of endoscopy-associated infections.
Angiotensin II and Anti Diuretic Hormone Exert Synergistic Effects on Thick Ascending Limb Transport in Spontaneously Hypertensive Rats
Authors: Silva Guillermo B. , Juncos Luis I. , Garcia Néstor H.
Published: February 2016

Background: Sodium reabsorption is increased in the thick ascending limb (TAL) of Henle in several hypertensive models. In this segment, while transport is increased by ADH via cAMP, sodium reabsorption results from Ang II-induced superoxide (O2-) production. Surprisingly, it is unknown whether these mechanisms overlap in hypertension. We hypothesized that Ang II and ADH have accumulative effects on TAL's transport during hypertension. Methods: The effect of ADH/Ang II in TALs from spontaneously hypertensive rats (SHR) on oxygen consumption (QO2), cAMP and O2- was measured. Results: Basal QO2 was 113.3 ± 14.2 nmol O2/min/mg protein. Addition of ADH (1 nM) increased QO2 by 198%. In the presence of ADH, Ang II (1 nM) elicited a QO2 transient response and then rose to 321.5 ± 28.3 (p = 0.003 vs. ADH). These accumulative effects could be due to nitric oxide synthase (NOS) uncoupling, lower Ang II ability to decrease cAMP or increased O2-. We first measured QO2 using a NOS inhibitor. Pretreatment with L-NAME did not block the observed interaction (p = 0.001 Ang II vs. ADH). Also, Ang II blocked the ADH-stimulated cAMP accumulation in TAL of SHRs. In the presence of ADH, Ang II increased O2- production in TALs from SHR by 309% (p = 0.015 vs. basal). The O2- scavenger tempol blocked the Ang II effects on QO2. In the presence of the NADPH oxidase inhibitor apocynin, the accumulative effects of ADH and Ang II were abolished. We conclude that (1) in SHR, Ang II has accumulative effects on ADH-stimulated transport; (2) this effect is mediated by AT1 receptors, and increased O2- production.
Tolerability and Healthcare Utilization in Maintenance Hemodialysis Patients Undergoing Treatment for Tuberculosis-Related Conditions
Authors: Hamadah Abdurrahman M. , Beaulieu Lynn M. , Wilson John W. , Aksamit Timothy R. , Gregoire James R. , Williams Amy W. , Dillon John J. , Albright Robert C. , Onuigbo Macaulay , Iyer Venkateshwaran K. , Hickson LaTonya J.
Published: February 2016

Background: The incidence of tuberculosis (TB) in end-stage renal disease is significantly higher than that in the general population. Among those with kidney dysfunction, anti-TB treatment is associated with increased side effects, but the effect on healthcare utilization is unknown. Methods/Aim: To assess patient-reported symptoms, adverse effects and describe changes in healthcare utilization patterns during treatment for TB, we conducted a case series (n = 12) of patients receiving maintenance hemodialysis (HD) from Mayo Clinic Dialysis Services and concurrent drug therapy for TB from January 2002 through May 2014. Healthcare utilization (hospitalizations and emergency department (ED) visits independent of hospital admission) was compared before and during treatment. Results: Patients were treated for latent (n = 7) or active (n = 5) TB. The majority of patients with latent disease were treated with isoniazid (n = 5, 71%), while active-disease patients received a 4-drug regimen. Adverse effects were reported in 83% of patients. Compared to measurements prior to drug initiation, serum albumin and dialysis weights were similar at 3 months. Commonly reported anti-TB drug toxicities were described. More than half (58%) of the patients were hospitalized at least once. No ED or hospital admissions occurred in the period prior to drug therapy, but healthcare utilization increased during treatment in the latent disease group (hospitalization rate per person-month: pre 0 vs. post 1). Conclusions: Among HD patients, anti-TB therapy is associated with frequently reported symptoms and increased healthcare utilization. Among this subset, patients receiving treatment for latent disease may be those with greatest increase in healthcare use. Careful monitoring and early complication detection may help optimize medication adherence and minimize hospitalizations.
Targeted Therapy of HER2-Negative Breast Cancer
Authors: Schütz Florian , Domschke Christoph , Schneeweiss Andreas
Published: February 2016

Personalized and targeted treatments are the most discussed topics in oncology. However, how much personalized medicine is standard of care nowadays and how much is part of our hope for a better future? So far, only a few targeted therapies are available in daily practice for the treatment of human epidermal growth factor receptor 2 (HER2)-negative breast cancer. And even for these few targeted agents - besides those targeting the estrogen receptor (ER) for endocrine treatment - thus far, predictive factors are missing. There are many new drugs and strategies under evaluation but, unfortunately, they are being developed without any cross-comparison. What drug will we choose for which patient in the future? Without answering this question oncologists will not be able to individualize treatment. Predictive factors for every new splendid drug are eagerly needed before it comes to an approval.
Durable Benefits of Cellular Postconditioning: Long‐Term Effects of Allogeneic Cardiosphere‐Derived Cells Infused After Reperfusion in Pigs with Acute Myocardial Infarction
Authors: Kanazawa Hideaki , Tseliou Eleni , Dawkins James F. , De Couto Geoffrey , Gallet Romain , Malliaras Konstantinos , Yee Kristine , Kreke Michelle , Valle Ileana , Smith Rachel R. , Middleton Ryan C. , Ho Chak‐Sum , Dharmakumar Rohan , Li Debiao , Makkar Raj R. , Fukuda Keiichi , Marbán Linda , Marbán Eduardo
Published: February 2016

Background

Infusion of allogeneic cardiosphere‐derived cells (allo‐
CDC
s) postreperfusion elicits cardioprotective cellular postconditioning in pigs with acute myocardial infarction. However, the long‐term effects of allo‐
CDC
s have not been assessed. We performed a placebo‐controlled pivotal study for long‐term evaluation, as well as shorter‐term mechanistic studies.

Methods and Results

Minipigs underwent 1.5‐hour mid‐left anterior descending balloon occlusion followed by reperfusion and were randomized to receive intracoronary allo‐
CDC
s or vehicle 30 minutes postreperfusion. Left ventriculography (
LVG
) demonstrated preserved ejection fraction (
EF
) and attenuation of
LV
remodeling in
CDC
‐treated pigs. Pigs underwent cardiac magnetic resonance imaging (
MRI
) and
LVG
1 hour and 8 weeks after therapy to evaluate efficacy.
MRI
showed improvement of
EF
and attenuation of
LV
remodeling immediately after allo‐
CDC
infusion. In addition, allo‐
CDC
s improved regional function and decreased hypertrophy 2 months post‐treatment. Histological analysis revealed increased myocardial salvage index, enhanced vascularity, sustained reductions in infarct size/area at risk and scar transmurality, and attenuation of collagen deposition in the infarct zone of allo‐
CDC
‐treated pigs at 2 months. Allo‐
CDC
s did not evoke lymphohistiocytic infiltration or systemic humoral memory response. Short‐term experiments designed to probe mechanism revealed antiapoptotic effects of allo‐
CDC
s on cardiomyocytes and increases in cytoprotective macrophages, but no increase in overall inflammatory cell infiltration 2 hours after cell therapy.

Conclusions

Allo‐
CDC
infusion postreperfusion is safe, improves cardiac function, and attenuates scar size and remodeling. The favorable effects persist for at least 2 months after therapy. Thus, cellular postconditioning confers not only acute cardioprotection, but also lasting structural and functional benefits.