bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporating User Expectations and Behavior into the Measurement of Search Effectiveness
Authors: Moffat Alistair , Bailey Peter , Scholer Falk , Thomas Paul
Published: June 2017

Information retrieval systems aim to help users satisfy information needs. We argue that the goal of the person using the system, and the pattern of behavior that they exhibit as they proceed to attain that goal, should be incorporated into the methods and techniques used to evaluate the effectiveness of IR systems, so that the resulting effectiveness scores have a useful interpretation that corresponds to the users’ search experience. In particular, we investigate the role of search task complexity, and show that it has a direct bearing on the number of relevant answer documents sought by users in response to an information need, suggesting that useful effectiveness metrics must be
goal sensitive
. We further suggest that user behavior while scanning results listings is affected by the rate at which their goal is being realized, and hence that appropriate effectiveness metrics must be
adaptive
to the presence (or not) of relevant documents in the ranking. In response to these two observations, we present a new effectiveness metric, INST, that has both of the desired properties: INST employs a parameter
T
, a direct measure of the user’s search goal that adjusts the top-weightedness of the evaluation score; moreover, as progress towards the target
T
is made, the modeled user behavior is adapted, to reflect the remaining expectations. INST is experimentally compared to previous effectiveness metrics, including Average Precision (AP), Normalized Discounted Cumulative Gain (NDCG), and Rank-Biased Precision (RBP), demonstrating our claims as to INST’s usefulness. Like RBP, INST is a weighted-precision metric, meaning that each score can be accompanied by a
residual
that quantifies the extent of the score uncertainty caused by unjudged documents. As part of our experimentation, we use crowd-sourced data and score residuals to demonstrate that a wide range of queries arise for even quite specific information needs, and that these variant queries introduce significant levels of residual uncertainty into typical experimental evaluations. These causes of variability have wide-reaching implications for experiment design, and for the construction of test collections.
Encoding Syntactic Knowledge in Neural Networks for Sentiment Classification
Authors: Huang Minlie , Qian Qiao , Zhu Xiaoyan
Published: June 2017

Phrase/Sentence representation is one of the most important problems in natural language processing. Many neural network models such as Convolutional Neural Network (CNN), Recursive Neural Network (RNN), and Long Short-Term Memory (LSTM) have been proposed to learn representations of phrase/sentence, however, rich syntactic knowledge has not been fully explored when composing a longer text from its shorter constituent words. In most traditional models, only word embeddings are utilized to compose phrase/sentence representations, while the syntactic information of words is yet to be explored. In this article, we discover that encoding syntactic knowledge (part-of-speech tag) in neural networks can enhance sentence/phrase representation. Specifically, we propose to learn tag-specific composition functions and tag embeddings in recursive neural networks, and propose to utilize POS tags to control the gates of tree-structured LSTM networks. We evaluate these models on two benchmark datasets for sentiment classification, and demonstrate that improvements can be obtained with such syntactic knowledge encoded.
Tritrophic Interactions: Microbe-Mediated Plant Effects on Insect Herbivores
Authors: Shikano Ikkei , Rosa Cristina , Tan Ching-Wen , Felton Gary W.
Published: June 2017

It is becoming abundantly clear that the microbes associated with plants and insects can profoundly influence plant-insect interactions. Here, we focus on recent findings and propose directions for future research that involve microbe-induced changes to plant defenses and nutritive quality as well as the consequences of these changes for the behavior and fitness of insect herbivores. Insect (herbivore and parasitoid)-associated microbes can favor or improve insect fitness by suppressing plant defenses and detoxifying defensive phytochemicals. Phytopathogens can influence or manipulate insect behavior and fitness by altering plant quality and defense. Plant-beneficial microbes can promote plant growth and influence plant nutritional and phytochemical composition that can positively or negatively influence insect fitness. Lastly, we suggest that entomopathogens have the potential to influence plant defenses directly as endophytes or indirectly by altering insect physiology.
CNS β3-adrenergic receptor activation regulates feeding behavior, white fat browning, and body weight
Authors: Richard Jennifer E. , López-Ferreras Lorena , Chanclón Belén , Eerola Kim , Micallef Peter , Skibicka Karolina P. , Wernstedt Asterholm Ingrid
Published: June 2017

Pharmacological β3-adrenergic receptor (β3AR) activation leads to increased mitochondrial biogenesis and activity in white adipose tissue (WAT), a process commonly referred to as “browning”, and transiently increased insulin release. These effects are associated with improved metabolic function and weight loss. It is assumed that this impact of β3AR agonists is mediated solely through activation of β3ARs in adipose tissue. However, β3ARs are also found in the brain, in areas such as the brain stem and the hypothalamus, which provide multisynaptic innervation to brown and white adipose depots. Thus, contrary to the current adipocentric view, the central nervous system (CNS) may also have the ability to regulate energy balance and metabolism through actions on central β3ARs. Therefore, this study aimed to elucidate whether CNS β3ARs can regulate browning of WAT and other aspects of metabolic regulation, such as food intake control and insulin release. We found that acute central injection of β3AR agonist potently reduced food intake, body weight, and increased hypothalamic neuronal activity in rats. Acute central β3AR stimulation was also accompanied by a transient increase in circulating insulin levels. Moreover, subchronic central β3AR agonist treatment led to a browning response in both inguinal (IWAT) and gonadal WAT (GWAT), along with reduced GWAT and increased BAT mass. In high-fat, high-sugar-fed rats, subchronic central β3AR stimulation reduced body weight, chow, lard, and sucrose water intake, in addition to increasing browning of IWAT and GWAT. Collectively, our results identify the brain as a new site of action for the anorexic and browning impact of β3AR activation.
Syk Plays a Critical Role in the Expression and Activation of IRAK1 in LPS-Treated Macrophages
Authors: Park Jae Gwang , Son Young-Jin , Yoo Byong Chul , Yang Woo Seok , Kim Ji Hye , Kim Jong-Hoon , Cho Jae Youl
Published: June 2017

To address how interleukin-1 receptor-associated kinase 1 (IRAK1) is controlled by other enzymes activated by toll-like receptor (TLR) 4, we investigated the possibility that spleen tyrosine kinase (Syk), a protein tyrosine kinase that is activated at an earlier stage during TLR4 activation, plays a central role in regulating the functional activation of IRAK1. Indeed, we found that overexpression of myeloid differentiation primary response gene 88 (MyD88), an adaptor molecule that drives TLR signaling, induced IRAK1 expression and that piceatannol, a Syk inhibitor, successfully suppressed the MyD88-dependent upregulation of IRAK1 under LPS treatment conditions. Interestingly, in Syk-knockout RAW264.7 cells, IRAK1 activity was almost completely blocked after LPS treatment, while providing a Syk-recovery gene to the knockout cells successfully restored IRAK1 expression. According to our measurements of IRAK1 mRNA levels, the transcriptional upregulation of IRAK1 was induced by LPS treatment between 4 and 60 min, and this can be suppressed in Syk knockout cells, providing an effect similar that that seen under piceatannol treatment. The overexpression of Syk reverses this effect and leads to a significantly higher IRAK1 mRNA level. Collectively, our results strongly suggest that Syk plays a critical role in regulating both the activity and transcriptional level of IRAK1.
Validation of a Liquid Chromatography-Tandem Mass Spectrometric Assay for Quantitative Analysis of Lenvatinib in Human Plasma
Authors: Ogawa-Morita Tomoko , Sano Yoshiyuki , Okano Tomoka , Fujii Hirofumi , Tahara Makoto , Yamaguchi Masakazu , Minami Hironobu
Published: June 2017

Toward conducting clinical pharmacokinetic studies of an antineoplastic agent, lenvatinib, we developed a liquid chromatography-tandem mass spectrometric assay for its quantitative analysis in human plasma. Analyte (lenvatinib) and internal standard (IS, propranolol) in the plasma were extracted by using acetonitrile and chromatographically separated by using a XTerra MS C18 column with 0.2 mL/min flow and mobile phase starting with 0.1% formic acid in water, followed by increasing percentage of acetonitrile. Detection was performed by using combined reversed-phase liquid chromatography-tandem mass spectrometry (LC/MS-MS) with positive ion electrospray ionization. MS-MS ion transitions used were 427.602>371.000 for lenvatinib and 260.064>116.005 for IS. This study was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification, recovery, and matrix effect according to the Guideline on Bioanalytical Method Validation in Pharmaceutical Development in Japan. Calibration curve was plotted by using lenvatinib concentrations ranging within 9.6–200 ng/mL, and correlation coefficients (r2) were in excess of 0.997. Intra- and interday accuracy ranged within 95.8–108.3% with mean recoveries of 66.8% for lenvatinib, and precision was <6.7% at all quality control concentration levels. Matrix effect analysis showed extraction efficiency of 15.7% for lenvatinib. Collectively, these findings demonstrate the feasibility of this method to evaluate kinetic disposition of lenvatinib.
Fibered Confocal Fluorescence Microscopy for the Noninvasive Imaging of Langerhans Cells in Macaques
Authors: Todorova Biliana , Salabert Nina , Tricot Sabine , Boisgard Raphaël , Rathaux Mélanie , Le Grand Roger , Chapon Catherine
Published: June 2017

Purpose. We developed a new approach to visualize skin Langerhans cells by in vivo fluorescence imaging in nonhuman primates. Procedures. Macaques were intradermally injected with a monoclonal, fluorescently labeled antibody against HLA-DR molecule and were imaged for up to 5 days by fibered confocal microscopy (FCFM). Results. The network of skin Langerhans cells was visualized by in vivo fibered confocal fluorescence microscopy. Quantification of Langerhans cells revealed no changes to cell density with time. Ex vivo experiments confirmed that injected fluorescent HLA-DR antibody specifically targeted Langerhans cells in the epidermis. Conclusions. This study demonstrates the feasibility of single-cell, in vivo imaging as a noninvasive technique to track Langerhans cells in nontransgenic animals.
Add‐On Therapy with Traditional Chinese Medicine Improves Outcomes and Reduces Adverse Events in Hepatocellular Carcinoma: A Meta‐Analysis of Randomized Controlled Trials
Authors: Yang Zongguo , Liao Xian , Lu Yunfei , Xu Qingnian , Tang Bozong , Chen Xiaorong , Yu Yongchun
Published: June 2017

Background and Aims. Traditional Chinese medicine (TCM) therapy for hepatocellular carcinoma remains controversial. This study aimed to evaluate the efficacy and safety of TCM regimens in HCC treatment. Methods. Randomized controlled trials (RCTs) up to June 1, 2016, of the TCM treatment for hepatocellular carcinoma were systematically identified in PubMed, CNKI, Ovid, Embase, Web of Science, Wanfang, VIP, CBM, AMED, and Cochrane Library databases. Results. A total of 1010 and 931 patients in 20 RCTs were randomly treated with add‐on TCM therapy and conventional therapy, respectively. The additional use of TCM significantly improved six‐month, one‐year, two‐year, and three‐year overall survival rates in HCC cases (RR = 1.3, P = 0.01; RR = 1.38, P = 0.0008; RR = 1.44, P < 0.0001; RR = 1.31, P = 0.02, resp.). Add‐on TCM therapy significantly increased PR rate and total response rate (tRR) and reduced PD rate compared to those in control group (34.4% versus 26.3%, RR = 1.30, P = 0.002; 41.6% versus 31.0%, RR = 1.30, P < 0.0001; and 16.6% versus 26.5%, RR = 0.64, P < 0.0001, resp.). Additionally, TCM combination therapy significantly increased the quality of life (QOL) improvement rate and reduced adverse events including leukopenia, thrombocytopenia, anemia or erythropenia, liver injury, and gastrointestinal discomfort in HCC patients (all P < 0.05). Conclusion. Add‐on therapy with TCM could improve overall survival, increase clinical tumor responses, lead to better QOL, and reduce adverse events in hepatocellular carcinoma.
Small Incision Lenticule Extraction for Correction of Myopia and Myopic Astigmatism: First 24-Hour Outcomes
Authors: Liu Taixiang , Dan Tingting , Luo Yan
Published: June 2017

Purpose. To observe the first 24-hour (h) outcomes of the small incision lenticule extraction procedure (SMILE) for myopia and myopic astigmatism.Methods. Fifty-three eyes (27 patients) scheduled for SMILE were followed immediately (0 h), 2, 4, 6, and 24 h after SMILE. Uncorrected visual acuity (UCVA), conjunctival congestion, pain level, and corneal edema, thickness, and densitometry were recorded.Results. At 2 h after SMILE, 15.1% of eyes had ≤0.1 LogMAR UCVA; this increased to 62.3%, 98.1%, and 100% at 4, 6, and 24 h, respectively. Some eyes (33.96%) had mild corneal edema immediately after surgery. No 6 h postoperative edema was observed. In the first 24 h after SMILE, corneal thickness gradually decreased. Postoperative corneal densitometry values were significantly higher than preoperative values but gradually decreased during the first postoperative 24 h.Conclusions. In the first postoperative 24 h, UCVA and corneal status (edema and densitometry) improved quickly.
miR‐Let7A Controls the Cell Death and Tight Junction Density of Brain Endothelial Cells under High Glucose Condition
Authors: Song Juhyun , Yoon So Ra , Kim Oh Yoen
Published: June 2017

Hyperglycemia‐induced stress in the brain of patients with diabetes triggers the disruption of blood‐brain barrier (BBB), leading to diverse neurological diseases including stroke and dementia. Recently, the role of microRNA becomes an interest in the research for deciphering the mechanism of brain endothelial cell damage under hyperglycemia. Therefore, we investigated whether mircoRNA Let7A (miR‐Let7A) controls the damage of brain endothelial (bEnd.3) cells against high glucose condition. Cell viability, cell death marker expressions (p‐53, Bax, and cleaved poly ADP‐ribose polymerase), the loss of tight junction proteins (ZO‐1 and claudin‐5), proinflammatory response (interleukin‐6, tumor necrosis factor‐α), inducible nitric oxide synthase, and nitrite production were confirmed using MTT, reverse transcription‐PCR, quantitative‐PCR, Western blotting, immunofluorescence, and Griess reagent assay. miR‐Let7A overexpression significantly prevented cell death and loss of tight junction proteins and attenuated proinflammatory response and nitrite production in the bEnd.3 cells under high glucose condition. Taken together, we suggest that miR‐Let7A may attenuate brain endothelial cell damage by controlling cell death signaling, loss of tight junction proteins, and proinflammatory response against high glucose stress. In the future, the manipulation of miR‐Let7A may be a novel solution in controlling BBB disruption which leads to the central nervous system diseases.
Lymphangiogenesis in Oral Squamous Cell Carcinoma: Correlation with VEGF-C Expression and Lymph Node Metastasis
Authors: Abdul-Aziz Manar A. , Amin Amina K. , El-Rouby Dalia H. , Shaker Olfat G.
Published: June 2017

Background.Oral squamous cell carcinoma (OSCC) is the most common oral malignancy that preferentially spreads to the cervical lymph node which, when involved, complicates the anticancer therapy and threatens the patient life. It was suggested that lymph node metastasis may be facilitated by lymphangiogenesis. VEGF-C is one of the most important lymphangiogenic inducers that promotes the lymphatic vessels growth and supports the survival of adult lymphatic endothelial cells.Methods. Lymphatic vessels density (LVD) and LV morphometry were digitally evaluated using D2-40. The expression of VEGF-C was also assessed using immunohistochemistry and real-time polymerase chain reaction in 6 normal oral mucosa cases and 72 cases of OSCC. The correlation between LVD and LV morphometry, VEGF-C, and lymph node metastasis was statistically assessed.Results. A positive cytoplasmic expression of VEGF-C was detected in both epithelial and connective tissue cells in 97% of OSCC, while all normal tissues reacted negatively. A greater expression of VEGF-C was associated with larger and more dilated LV and lymph node metastasis but not with LVD.Conclusion. VEGF-C is actively involved in the invasion and metastasis of OSCC via inducing morphological changes in LV. VEGF-C may be a promising target for anticancer therapy.
Improving the Fine-Tuning of Metaheuristics: An Approach Combining Design of Experiments and Racing Algorithms
Authors: Barbosa Eduardo Batista de Moraes , Senne Edson Luiz França
Published: June 2017

Usually, metaheuristic algorithms are adapted to a large set of problems by applying few modifications on parameters for each specific case. However, this flexibility demands a huge effort to correctly tune such parameters. Therefore, the tuning of metaheuristics arises as one of the most important challenges in the context of research of these algorithms. Thus, this paper aims to present a methodology combining Statistical and Artificial Intelligence methods in the fine-tuning of metaheuristics. The key idea is a heuristic method, called Heuristic Oriented Racing Algorithm (HORA), which explores a search space of parameters looking for candidate configurations close to a promising alternative. To confirm the validity of this approach, we present a case study for fine-tuning two distinct metaheuristics: Simulated Annealing (SA) and Genetic Algorithm (GA), in order to solve the classical traveling salesman problem. The results are compared considering the same metaheuristics tuned through a racing method. Broadly, the proposed approach proved to be effective in terms of the overall time of the tuning process. Our results reveal that metaheuristics tuned by means of HORA achieve, with much less computational effort, similar results compared to the case when they are tuned by the other fine-tuning approach.
Mitochondrial Nucleoid: Shield and Switch of the Mitochondrial Genome
Authors: Lee Sung Ryul , Han Jin
Published: June 2017

Mitochondria preserve very complex and distinctively unique machinery to maintain and express the content of mitochondrial DNA (mtDNA). Similar to chromosomes, mtDNA is packaged into discrete mtDNA‐protein complexes referred to as a nucleoid. In addition to its role as a mtDNA shield, over 50 nucleoid‐associated proteins play roles in mtDNA maintenance and gene expression through either temporary or permanent association with mtDNA or other nucleoid‐associated proteins. The number of mtDNA(s) contained within a single nucleoid is a fundamental question but remains a somewhat controversial issue. Disturbance in nucleoid components and mutations in mtDNA were identified as significant in various diseases, including carcinogenesis. Significant interest in the nucleoid structure and its regulation has been stimulated in relation to mitochondrial diseases, which encompass diseases in multicellular organisms and are associated with accumulation of numerous mutations in mtDNA. In this review, mitochondrial nucleoid structure, nucleoid‐associated proteins, and their regulatory roles in mitochondrial metabolism are briefly addressed to provide an overview of the emerging research field involving mitochondrial biology.
Roles of Cells from the Arterial Vessel Wall in Atherosclerosis
Authors: Wang Di , Wang Zhiyan , Zhang Lili , Wang Yi
Published: June 2017

Atherosclerosis has been identified as a chronic inflammatory disease of the arterial vessel wall. Accumulating evidence indicates that different cells from the tunica intima, media, adventitia, and perivascular adipose tissue not only comprise the intact and normal arterial vessel wall but also participate all in the inflammatory response of atherosclerosis via multiple intricate pathways. For instance, endothelial dysfunction has historically been considered to be the initiator of the development of atherosclerosis. The migration and proliferation of smooth muscle cells also play a pivotal role in the progression of atherosclerosis. Additionally, the fibroblasts from the adventitia and adipocytes from perivascular adipose tissue have received considerable attention given their special functions that contribute to atherosclerosis. In addition, numerous types of cytokines produced by different cells from the arterial vessel wall, including endothelium-derived relaxing factors, endothelium-derived contracting factors, tumor necrosis factors, interleukin, adhesion molecules, interferon, and adventitium-derived relaxing factors, have been implicated in atherosclerosis. Herein, we summarize the possible roles of different cells from the entire arterial vessel wall in the pathogenesis of atherosclerosis.
Gas Sensing Properties of NiSb2O6 Micro- and Nanoparticles in Propane and Carbon Monoxide Atmospheres
Authors: Rodríguez-Betancourtt Verónica-M. , Bonilla Héctor Guillén , Flores Martínez Martín , Guillén Bonilla Alex , Moran Lazaro J. P. , Bonilla José Trinidad Guillen , González M. A. , de la Luz Olvera Amador María
Published: June 2017

Micro- and nanoparticles of NiSb2O6 were synthesized by the microwave-assisted colloidal method. Nickel nitrate, antimony chloride, ethylenediamine, and ethyl alcohol were used. The oxide was obtained at 600°C and was analyzed by X-ray diffraction (XRD) and Raman spectroscopy, showing a trirutile-type structure with cell parameters a = 4.641 Å, c = 9.223 Å, and a space group P42/mnm (136). Average crystal size was estimated at ~31.19 nm, according to the XRD-peaks. The microstructure was scrutinized by scanning electron microscopy (SEM), observing microrods measuring ~3.32 μm long and ~2.71 μm wide, and microspheres with an average diameter of ~8 μm; the size of the particles shaping the microspheres was measured in the range of ~0.22 to 1.8 μm. Transmission electron microscopy (TEM) revealed that nanoparticles were obtained with sizes in the range of 2 to 20 nm (~10.7 nm on average). Pellets made of oxide’s powders were tested in propane (C3H8) and carbon monoxide (CO) atmospheres at different concentrations and temperatures. The response of the material increased significantly as the temperature and the concentration of the test gases rose. These results show that NiSb2O6 may be a good candidate for gas sensing applications.
Experimental Study on Structural Performance of RC Exterior Beam-Column Joints Retrofitted by Steel Jacketing and Haunch Element under Cyclic Loading Simulating Earthquake Excitation
Authors: Dang Cong-Thuat , Dinh Ngoc-Hieu
Published: June 2017

Several retrofitting methods for reinforced concrete (RC) beam-column joints in old buildings without seismic details were developed. Four half-scale RC exterior beam-column joints were fabricated and tested under cyclic loading simulating earthquake excitation. The control specimen was designed to fail in joint shear. Two practical retrofitting strategies were applied to the control specimen which consider the architectural characteristic in real buildings, including steel jacketing and haunch retrofit solution. The structural performance of the test specimens was investigated in terms of various factors including damage and failure, load-drift relationship, ductility, dissipated energy, and strain profiles of longitudinal reinforcement. Experimental results confirmed that the proposed retrofit methods were shown to enhance the seismic capacity of the joints in terms of the strength, deformation capacity, and energy dissipation capacity while the shear deformation in the panel zone significantly reduced in comparison with the control specimen.
Association between Aqueous Cytokines and Diabetic Retinopathy Stage
Authors: Wu Hailiang , Hwang De-Kuang , Song Xudong , Tao Yong
Published: June 2017

Purpose.To measure the concentrations of various cytokines in the aqueous humor from patients with different stages of diabetic retinopathy.Methods.All selected cataract patients were categorized into 4 groups: the control group (patients without diabetes), nonretinopathy (NDR) group (diabetic patients without retinopathy), nonproliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. The aqueous concentrations of interleukin- (IL-) 1β, IL-2, IL-4, IL-5, IL-6, IL-10, interferon-γ, tumor necrosis factor-α, and vascular endothelial growth factor (VEGF) from patients were measured using the cytometric bead array technique.Results.In this study, 10, 22, 15, and 14 patients were included in the control, NDR, NPDR, and PDR groups, respectively. No difference was observed in the aqueous concentrations of all cytokines between the control group and the NDR group. By contrast, comparison of these groups revealed that the aqueous concentrations of most inflammatory cytokines were significantly higher in the PDR and NPDR groups. In addition, the concentrations of IL-2, IL-5, and VEGF were higher in the PDR group than those in the NPDR group.Conclusions.Aqueous concentrations of various cytokines increased with the severity of patients’ diabetic retinopathy. This finding implies that these cytokines might play a role in the progression of diabetic retinopathy.
Video-Assisted Anal Fistula Treatment: Pros and Cons of This Minimally Invasive Method for Treatment of Perianal Fistulas
Authors: Romaniszyn Michal , Walega Piotr
Published: June 2017

Purpose. The purpose of this paper is to present results of a single-center, nonrandomized, prospective study of the video-assisted anal fistula treatment (VAAFT). Methods. 68 consecutive patients with perianal fistulas were operated on using the VAAFT technique. 30 of the patients had simple fistulas, and 38 had complex fistulas. The mean follow-up time was 31 months. Results. The overall healing rate was 54.41% (37 of the 68 patients healed with no recurrence during the follow-up period). The results varied depending on the type of fistula. The success rate for the group with simple fistulas was 73.3%, whereas it was only 39.47% for the group with complex fistulas. Female patients achieved higher healing rates for both simple (81.82% versus 68.42%) and complex fistulas (77.78% versus 27.59%). There were no major complications. Conclusions. The results of VAAFT vary greatly depending on the type of fistula. The procedure has some drawbacks due to the rigid construction of the fistuloscope and the diameter of the shaft. The electrocautery of the fistula tract from the inside can be insufficient to close wide tracts. However, low risk of complications permits repetition of the treatment until success is achieved. Careful selection of patients is advised.
Exosome-Derived miR-25-3p and miR-92a-3p Stimulate Liposarcoma Progression
Authors: Casadei Lucia , Calore Federica , Creighton Chad J. , Guescini Michele , Batte Kara , Iwenofu O. Hans , Zewdu Abeba , Braggio Danielle A. , Bill Kate Lynn , Fadda Paolo , Lovat Francesca , Lopez Gonzalo , Gasparini Pierluigi , Chen James L. , Kladney Raleigh D. , Leone Gustavo , Lev Dina , Croce Carlo M. , Pollock Raphael E.
Published: June 2017

Despite the development of combined modality treatments against liposarcoma in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by liposarcoma cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25-3p and miR-92a-3p stimulated secretion of proinflammatory cytokine IL6 from tumor-associated macrophages in a TLR7/8-dependent manner, which in turn promoted liposarcoma cell proliferation, invasion, and metastasis via this interaction with the surrounding microenvironment. Our findings provide novel and previously unreported insight into liposarcoma progression, identifying communication between liposarcoma cells and their microenvironment as a process critically involved in liposarcoma progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy. Cancer Res; 77(14); 3846–56. ©2017 AACR.
The “Fetal Reserve Index”: Re-Engineering the Interpretation and Responses to Fetal Heart Rate Patterns
Authors: Eden Robert D. , Evans Mark I. , Evans Shara M. , Schifrin Barry S.
Published: June 2017

Objective: Electronic fetal monitoring (EFM) correlates poorly with neonatal outcome. We present a new metric: the “Fetal Reserve Index” (FRI), formally incorporating EFM with maternal, obstetrical, fetal risk factors, and excessive uterine activity for assessment of risk for cerebral palsy (CP). Methods: We performed a retrospective, case-control series of 50 term CP cases with apparent intrapartum neurological injury and 200 controls. All were deemed neurologically normal on admission. We compared the FRI against ACOG Category (I-III) system and long-term outcome parameters against ACOG monograph (NEACP) requirements for labor-induced fetal neurological injury. Results: Abnormal FRI's identified 100% of CP cases and did so hours before injury. ACOG Category III identified only 44% and much later. Retrospective ACOG monograph criteria were found in at most 30% of intrapartum-acquired CP patients; only 27% had umbilical or neonatal pH <7.0. Conclusions: In this initial, retrospective trial, an abnormal FRI identified all cases of labor-related neurological injury more reliably and earlier than Category III, which may allow fetal therapy by intrauterine resuscitation. The combination of traditional EFM with maternal, obstetrical, and fetal risk factors creating the FRI performed much better as a screening test than EFM alone. Our quantified screening system needs further evaluation in prospective trials.
Physical Activity in End-Stage Renal Disease Patients: The Effects of Starting Dialysis in the First 6 Months after the Transition Period
Authors: Broers Natascha J.H. , Martens Remy J.H. , Cornelis Tom , van der Sande Frank M. , Diederen Nanda M.P. , Hermans Marc M.H. , Wirtz Joris J.J.M. , Stifft Frank , Konings Constantijn J.A.M. , Dejagere Tom , Canaud Bernard , Wabel Peter , Leunissen Karel M.L. , Kooman Jeroen P.
Published: June 2017

Objectives: Physical inactivity in end-stage renal disease (ESRD) patients is associated with increased mortality, and might be related to abnormalities in body composition (BC) and physical performance. It is uncertain to what extent starting dialysis influences the effects of ESRD on physical activity (PA). This study aimed to compare PA and physical performance between stage 5 chronic kidney disease (CKD-5) non-dialysis and dialysis patients, and healthy controls, to assess alterations in PA during the transition from CKD-5 non-dialysis to dialysis, and to relate PA to BC. Methods: For the cross-sectional analyses 44 CKD-5 non-dialysis patients, 29 dialysis patients, and 20 healthy controls were included. PA was measured by the SenseWear™ pro3. Also, the walking speed and handgrip strength (HGS) were measured. BC was measured by the Body Composition Monitor©. Longitudinally, these parameters were assessed in 42 CKD-5 non-dialysis patients (who were also part of the cross-sectional analysis), before the start of dialysis and 6 months thereafter. Results: PA was significantly lower in CKD-5 non-dialysis patients as compared to that in healthy controls but not as compared to that in dialysis patients. HGS was significantly lower in dialysis patients as compared to that in healthy controls. Walking speed was significantly lower in CKD-5 non-dialysis patients as compared to that in healthy controls but not as compared to that in dialysis patients. Six months after starting dialysis, activity related energy expenditure (AEE) and walking speed significantly increased. Conclusions: PA is already lower in CKD-5 non-dialysis patients as compared to that in healthy controls and does not differ from that of dialysis patients. However, the transition phase from CKD-5 non-dialysis to dialysis is associated only with a modest improvement in AEE.
A Novel Homozygous Missense FSHR Variant Associated with Hypergonadotropic Hypogonadism in Two Siblings from a Brazilian Family
Authors: França Monica M. , Lerario Antonio M. , Funari Mariana F.A. , Nishi Mirian Y. , Narcizo Amanda M. , de Mello Maricilda P. , Guerra-Junior Gil , Maciel-Guerra Andrea T. , Mendonça Berenice B.
Published: June 2017

Hypergonadotropic hypogonadism (HH) is defined by increased gonadotropin levels in men and women. Primary ovarian failure (POF) is a form of female infertility characterized by amenorrhea, hypoestrogenism, and elevated gonadotropin levels in women under the age of 40 years. Although several genes have been associated with POF, its causative genes remain to be identified. Here, we used whole-exome sequencing (WES) to study a consanguineous family with a 46,XX girl and a 46,XY man affected by HH. All exons of both siblings and their parents were captured and massively sequenced by WES, and the candidate variant was confirmed by Sanger sequencing. A novel c.1298C>A;p.Ala433Asp missense variant of the follicle-stimulating hormone receptor (FSHR) gene was found in both affected siblings in a homozygous state and in their parents in a heterozygous state. This FSHR variant is not present in available databases (1000 Genomes and NHLBI/EVS) and Brazilian exome controls. Moreover, it is highly conserved and predicted as deleterious in all prediction sites analyzed. In conclusion, the novel homozygous FSHR variant observed in 2 siblings with HH can expand the spectrum of FSHR mutations in humans.
Prognostic Accuracy of Mild Cognitive Impairment Subtypes at Different Cut-Off Levels
Authors: Göthlin Mattias , Eckerström Marie , Rolstad Sindre , Wallin Anders , Nordlund Arto
Published: June 2017

Background/Aims: The prognostic accuracy of mild cognitive impairment (MCI) in clinical settings is debated, variable across criteria, cut-offs, subtypes, and follow-up time. We aimed to estimate the prognostic accuracy of MCI and the MCI subtypes for dementia using three different cut-off levels. Methods: Memory clinic patients were followed for 2 (n = 317, age 63.7 ± 7.8) and 4-6 (n = 168, age 62.6 ± 7.4) years. We used 2.0, 1.5, and 1.0 standard deviations (SD) below the mean of normal controls (n = 120, age 64.1 ± 6.6) to categorize MCI and the MCI subtypes. Prognostic accuracy for dementia syndrome at follow-up was estimated. Results: Amnestic multi-domain MCI (aMCI-md) significantly predicted dementia under all conditions, most markedly when speed/attention, language, or executive function was impaired alongside memory. For aMCI-md, sensitivity increased and specificity decreased when the cut-off was lowered from 2.0 to 1.5 and 1.0 SD. Non-subtyped MCI had a high sensitivity and a low specificity. Conclusion: Our results suggest that aMCI-md is the only viable subtype for predicting dementia for both follow-up times. Lowering the cut-off decreases the positive predictive value and increases the negative predictive value of aMCI-md. The results are important for understanding the clinical prognostic utility of MCI, and MCI as a non-progressive disorder.
Booktrailers: novas formas de consumir livros e micronarrativas que capturam o leitor
Authors: Carvalho Dora
Published: June 2017

Os booktrailers são hoje uma das estratégias de divulgação de lançamentos literários no mercado, a fim de atrair o leitor para as tramas apresentadas nas novas obras. A partir de conceitos como bricolagem, ready-made, gêneros discursivos da publicidade, narrativas e memória, este estudo propõe uma discussão sobre as formas utilizadas pelos publicitários para persuadir o leitor a consumir novos livros. Os autores que nos ajudam nesta análise são João Anzanello Carrascoza, José Ortega y Gasset, John Thompson, Colin Campbell, Lluís Duch, Albert Chillón y Fredric Jameson.
Selos e Apelos: Fabricação da Imagem de Açúcar “Verde” e Agendamento
Authors: Paganotti Ivan , Marchesi Mariana De Toledo
Published: June 2017

Este artigo analisa a construção da imagem de marcas sustentáveis de açúcar a partir das informações e representações imagéticas utilizadas nas embalagens para o consumidor. A representação da consciência socioambiental diverge entre as empresas avaliadas: União, Native e Guarani, que se baseiam em estratégias diferentes de agendamento dos comportamentos dos consumidores, e só as duas primeiras fundamentam sua imagem em selos e certificados de instituições que avaliam a gestão sustentável dos produtos.
Accelerometer-Measured Daily Activity in Heart Failure With Preserved Ejection Fraction
Authors: Snipelisky David , Kelly Jacob , Levine James A. , Koepp Gabriel A. , Anstrom Kevin J. , McNulty Steven E. , Zakeri Rosita , Felker G. Michael , Hernandez Adrian F. , Braunwald Eugene , Redfield Margaret M.
Published: June 2017

Background—

Daily physical activity assessed by accelerometers represents a novel method to assess the impact of interventions on heart failure (HF) patients’ functional status. We hypothesized that daily activity varies by patient characteristics and correlates with established measures of HF severity in HF with preserved ejection fraction.

Methods and Results—

In this ancillary study of the NEAT-HFpEF trial (Nitrate’s Effects on Activity Tolerance in HF With Preserved Ejection Fraction), average daily accelerometer units (ADAU) and hours active per day were assessed during a 14-day period before starting isosorbide mononitrate or placebo (n=110). Baseline ADAU was negatively associated with age, female sex, height, and body mass index, and these variables accounted for 28% of the variability in ADAU (
P
<0.007 for all). Adjusting for these factors, patients with lower ADAU were more likely to have had an HF hospitalization, orthopnea, diabetes mellitus and anemia, be treated with β-blockers, have higher ejection fraction, relative wall thickness and left atrial volume, and worse New York Heart Association class, HF-specific quality of life scores, 6-minute walk distance, and NT-proBNP (N-terminal pro-B-type natriuretic peptide;
P
<0.05 for all). Associations between hours active per day and clinical characteristics were similar. Relative to baseline, there were no significant associations between changes in ADAU or hours active per day and changes in standard functional assessments (New York Heart Association, quality of life, 6-minute walk distance, and NT-proBNP) with isosorbide mononitrate.

Conclusions—

Daily activity is a measure of HF-related and global functional status in HF with preserved ejection fraction. As compared with intermittently assessed standard HF assessments, change in daily activity may provide unique information about the impact of HF interventions on functional status.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov/
. Unique identifier: NCT02053493
Associations of Abdominal Obesity and New‐Onset Atrial Fibrillation in the General Population
Authors: Baek Yong‐Soo , Yang Pil‐Sung , Kim Tae‐Hoon , Uhm Jae‐Sun , Park Junbeom , Pak Hui‐Nam , Lee Moon‐Hyoung , Joung Boyoung
Published: June 2017

Background

Higher height and weight are known to be associated with higher risk of atrial fibrillation (
AF
); however, whether the risk of
AF
is related to abdominal obesity is unclear.

Methods and Results

We studied 501 690 adults (mean age: 47.6±14.3 years; 250 664 women [50.0%]) without baseline
AF
in the National Sample Cohort released by the National Health Insurance Service in Korea. Body mass index (underweight defined as <18.5; normal, 18.5 to <25.0; overweight, 25.0 to <30.0; and obese, ≥30.0) and waist circumference (abdominal obesity defined as ≥90 cm for men and ≥80 cm for women) were evaluated. During a mean follow‐up of 3.9±1.3 years, 3443 participants (1432 women [41.6%]) developed
AF
. In multivariable models adjusted for clinical variables, the AF risk of underweight, overweight, and obese individuals increased by 21% (95% confidence interval, 1.01–1.45,
P
=0.043), 14% (95% confidence interval, 1.06–1.23,
P
<0.001), and 52% (95% confidence interval, 1.30–1.78,
P
<0.001), respectively, compared with those with normal body mass index.
AF
risk with confounder‐adjusted hazards for abdominal obesity was 18% (95% confidence interval, 1.10–1.27,
P
<0.001). The increased
AF
risk was present in abdominally obese individuals regardless of body mass index except for the obese group. In subgroup analysis, abdominal obesity by waist circumference conferred increased risk of new‐onset
AF
, particularly in participants without comorbidities.

Conclusions

Abdominal obesity is an important, potentially modifiable risk factor for
AF
in nonobese Asian persons. These data suggest that interventions to decrease abdominal obesity may reduce the population burden of
AF
.
Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus
Authors: Lee Chi Ho , Woo Yu Cho , Chow Wing Sun , Cheung Chloe Yu Yan , Fong Carol Ho Yi , Yuen Michele Mae Ann , Xu Aimin , Tse Hung Fat , Lam Karen Siu Ling
Published: June 2017

Background

Fibroblast growth factor 21 (
FGF
21) has demonstrated beneficial effects on lipid and carbohydrate metabolism. In cross‐sectional studies, an association of raised circulating
FGF
21 levels with coronary heart disease (
CHD
) was found in some but not all studies. Here we investigated prospectively whether baseline serum
FGF
21 levels could predict incident
CHD
in subjects with type 2 diabetes mellitus and no known cardiovascular diseases.

Methods and Results

Baseline serum
FGF
21 levels were measured in 3528 Chinese subjects with type 2 diabetes mellitus recruited from the Hong Kong West Diabetes Registry. The role of baseline serum
FGF
21 levels in predicting incident
CHD
over a median follow‐up of 3.8 years was analyzed using Cox regression analysis. Among 3528 recruited subjects without known cardiovascular diseases, 147 (4.2%) developed
CHD
over a mean follow‐up of 4 years. Baseline serum log‐transformed
FGF
21 levels were significantly higher in those who had incident
CHD
than those who did not (222.7 pg/mL [92.8–438.4] versus 151.1 pg/mL [75.6–274.6];
P
<0.001). On multivariable Cox regression analysis, baseline serum
FGF
21 levels, using an optimal cutoff of 206.22 pg/mL derived from our study, independently predicted incident
CHD
(hazard ratio, 1.55; 95% CI, 1.10–2.19;
P
=0.013) and significantly improved net reclassification index and integrated discrimination improvement after adjustment for conventional cardiovascular risk factors.

Conclusions

We have demonstrated, for the first time, that serum
FGF
21 level is an independent predictor of incident
CHD
and might be usefully utilized as a biomarker for identifying type 2 diabetes mellitus subjects with raised
CHD
risk, for primary prevention.
Associations Between Cardiac Troponin, Mechanism of Myocardial Injury, and Long‐Term Mortality After Noncardiac Vascular Surgery
Authors: Reed Grant W. , Horr Samuel , Young Laura , Clevenger Joshua , Malik Umair , Ellis Stephen G. , Lincoff A. Michael , Nissen Steven E. , Menon Venu
Published: June 2017

Background

The time‐sensitive hazard of perioperative cardiac troponin T (cTnT) elevation and whether long‐term mortality differs by mechanism of myocardial injury are poorly understood.

Methods and Results

In this observational study of 12 882 patients who underwent noncardiac vascular surgery, patients were assessed for cTnT sampling within 96 hours postoperatively. Mortality out to 5‐years was stratified by cTnT level and mechanism of myocardial injury. During a median follow‐up of 26.9 months, there were 2149 (16.7%) deaths. By multivariable Cox proportional hazards analysis, there was a graded increase in mortality with any detectable cTnT compared to <0.01 ng/mL; cTnT 0.01 to 0.029 ng/mL hazard ratio (HR) 1.54 (95% CI 1.18–2.00,
P
=0.002), 0.03 to 0.099 ng/mL HR 1.86 (95% CI 1.49–2.31,
P
<0.001), 0.10 to 0.399 ng/mL HR 1.83 (95% CI 1.46–2.31,
P
<0.001), ≥0.40 ng/mL HR 2.62 (95% CI 2.06–3.32,
P
<0.001). Mortality for each mechanism of injury was greater than for patients with normal cTnT; baseline cTnT elevation HR 1.71 (95% CI 1.31–2.24;
P
<0.001), Type 2 myocardial infarction HR 1.88 (95% CI 1.57–2.24;
P
<0.001), Type 1 MI HR 2.56 (95% CI 2.56, 1.82–3.60;
P
<0.001). On Kaplan–Meier analysis, long‐term survival did not differ between mechanisms. The hazard of mortality was greatest within the first 10 months postsurgery. Consistent results were obtained in confirmatory propensity‐score matched analyses.

Conclusions

Any detectable cTnT ≥0.01 ng/mL is associated with increased long‐term mortality after vascular surgery. This risk is greatest within the first 10 months postoperatively. While short‐term mortality is greatest with Type 1 myocardial infarction, long‐term mortality appears independent of the mechanism of injury.
Stunning and Right Ventricular Dysfunction Is Induced by Coronary Balloon Occlusion and Rapid Pacing in Humans: Insights From Right Ventricular Conductance Catheter Studies
Authors: Axell Richard G. , Giblett Joel P. , White Paul A. , Klein Andrew , Hampton‐Til James , O'Sullivan Michael , Braganza Denise , Davies William R. , West Nick E. J. , Densem Cameron G. , Hoole Stephen P.
Published: June 2017

Background

We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [
BO
]) and supply/demand ischemia (induced by rapid pacing [
RP
] during transcatheter aortic valve replacement) in humans.

Methods and Results

Ten subjects with single‐vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the
BO
group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the
RP
group. In both, a conductance catheter was placed into the right ventricle, and pressure volume loops were recorded at baseline and for intervals over 15 minutes after a low‐pressure
BO
for 1 minute or a cumulative duration of
RP
for up to 1 minute. Ischemia‐induced diastolic dysfunction was seen 1 minute after
RP
(end‐diastolic pressure [mm Hg]: 8.1±4.2 versus 12.1±4.1,
P
<0.001) and
BO
(end‐diastolic pressure [mm Hg]: 8.1
±
4.0 versus 8.7±4.0,
P
=0.03). Impairment of systolic and diastolic function after
BO
remained at 15‐minutes recovery (ejection fraction [%]: 55.7±9.0 versus 47.8±6.3,
P
<0.01; end‐diastolic pressure [mm Hg]: 8.1±4.0 versus 9.2±3.9,
P
<0.01). Persistent diastolic dysfunction was also evident in the
RP
group at 15‐minutes recovery (end‐diastolic pressure [mm Hg]: 8.1±4.1 versus 9.9±4.4,
P
=0.03) and there was also sustained impairment of load‐independent indices of systolic function at 15 minutes after
RP
(end‐systolic elastance and ventriculo‐arterial coupling [mm Hg/mL]: 1.25±0.31 versus 0.85±0.43,
P
<0.01).

Conclusions

RP and right coronary artery balloon occlusion both cause ischemic right ventricular dysfunction with stunning observed later during the procedure. This may have intraoperative implications in patients without right ventricular functional reserve.