bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell Detection Using Extremal Regions in a Semisupervised Learning Framework
Authors: Ramesh Nisha , Liu Ting , Tasdizen Tolga
Published: June 2017

This paper discusses an algorithm to build a semisupervised learning framework for detecting cells. The cell candidates are represented as extremal regions drawn from a hierarchical image representation. Training a classifier for cell detection using supervised approaches relies on a large amount of training data, which requires a lot of effort and time. We propose a semisupervised approach to reduce this burden. The set of extremal regions is generated using a maximally stable extremal region (MSER) detector. A subset of nonoverlapping regions with high similarity to the cells of interest is selected. Using the tree built from the MSER detector, we develop a novel differentiable unsupervised loss term that enforces the nonoverlapping constraint with the learned function. Our algorithm requires very few examples of cells with simple dot annotations for training. The supervised and unsupervised losses are embedded in a Bayesian framework for probabilistic learning.
Research on the Thermal Aging Behaviors of LDPE/TiO2 Nanocomposites
Authors: Liu Jun , Wang Youyuan , Xiao Kun , Zhang Zhanxi
Published: June 2017

The ability of antithermal aging of LDPE/TiO2 nanocomposites was investigated through SEM, FTIR, DSC, and dielectric properties in this paper. The results of SEM images showed that the thermal aging had a significant influence on the structure of Pure-LDPE and LDPE/TiO2 samples. The measurement of FTIR showed that the content of hydroxyl and carboxyl increased with thermal aging, but the time of emerging aging characteristic peaks for the LDPE/TiO2 samples was delayed. The DSC measurement indicated that filling TiO2 nanoparticles changed the crystallization behavior of LDPE, played a role of heterogeneous nucleation during the process of recrystallization, and improved the crystallinity of LDPE/TiO2. Similarly, the aged LDPE/TiO2 samples had lower permittivity and dissipation factor compared to the aged Pure-LDPE samples. All the results had indicated the LDPE/TiO2 samples had the significant ability of antithermal aging, especially the LDPE/TiO2-0.5 samples with good dispersion of nanoparticles. A new model was proposed to illustrate the antithermal aging behaviors of LDPE/TiO2 samples, which shows that the TiO2 nanoparticles play a role of “crosslinking points” between LDPE molecular chains, increasing the density of crystal structure and reducing oxygen diffusion into materials to break molecular structure.
An Experimental Study on Solute Transport in One-Dimensional Clay Soil Columns
Authors: Zaheer Muhammad , Wen Zhang , Zhan Hongbin , Chen Xiaolian , Jin Menggui
Published: June 2017

Solute transport in low-permeability media such as clay has not been studied carefully up to present, and we are often unclear what the proper governing law is for describing the transport process in such media. In this study, we composed and analyzed the breakthrough curve (BTC) data and the development of leaching in one-dimensional solute transport experiments in low-permeability homogeneous and saturated media at small scale, to identify key parameters controlling the transport process. Sodium chloride (NaCl) was chosen to be the tracer. A number of tracer tests were conducted to inspect the transport process under different conditions. The observed velocity-time behavior for different columns indicated the decline of soil permeability when switching from tracer introducing to tracer flushing. The modeling approaches considered were the Advection-Dispersion Equation (ADE), Two-Region Model (TRM), Continuous Time Random Walk (CTRW), and Fractional Advection-Dispersion Equation (FADE). It was found that all the models can fit the transport process very well; however, ADE and TRM were somewhat unable to characterize the transport behavior in leaching. The CTRW and FADE models were better in capturing the full evaluation of tracer-breakthrough curve and late-time tailing in leaching.
First Reported Case of Hemopericardium Related to Dabigatran Use Reversed by New Antidote Idarucizumab
Authors: Song Steven , Cook Joselle , Goulbourne Clive , Meade Matthew , Salciccioli Louis , Lazar Jason
Published: June 2017

Dabigatran, the first novel oral anticoagulant (NOAC) with a reversal agent, heralded a paradigm shift in the treatment of nonvalvular atrial fibrillation. The potential for life-threatening hemorrhagic events with the use of NOACs has been highly debated since the effectiveness of reversal agents such as idarucizumab is based primarily on pharmacologic data. It is known that cancer patients are at an increased risk of bleeding with anticoagulation, though specific studies demonstrating the risks or efficacy of NOACs in this population are lacking. We provide the first report of hemopericardium resulting in multiorgan failure related to dabigatran use that was successfully reversed by idarucizumab in a man with prostate cancer on chemotherapy.
Heme Oxygenase‐1, a Key Enzyme for the Cytoprotective Actions of Halophenols by Upregulating Nrf2 Expression via Activating Erk1/2 and PI3K/Akt in EA.hy926 Cells
Authors: Feng Xiu E. , Liang Tai Gang , Gao Jie , Kong De Peng , Ge Rui , Li Qing Shan
Published: June 2017

Increasing evidence has demonstrated that heme oxygenase‐1 (HO‐1) is a key enzyme triggered by cellular stress, exhibiting cytoprotective, antioxidant, and anti‐inflammatory abilities. Previously, we prepared a series of novel active halophenols possessing strong antioxidant activities in vitro and in vivo. In the present study, we demonstrated that these halophenols exhibited significant protective effects against H2O2‐induced injury in EA.hy926 cells by inhibition of apoptosis and ROS and TNF‐α production, as well as induction of the upregulation of HO‐1, the magnitude of which correlated with their cytoprotective actions. Further experiments which aimed to determine the mechanistic basis of these actions indicated that the halophenols induced the activation of Nrf2, Erk1/2, and PI3K/Akt without obvious effects on the phosphorylation of p38, JNK, or the expression of PKC‐δ. This was validated with the use of PD98059 and Wortmannin, specific inhibitors of Erk1/2 and PI3K, respectively. Overall, our study is the first to demonstrate that the cytoprotective actions of halophenols involve their antiapoptotic, antioxidant, and anti‐inflammatory abilities, which are mediated by the upregulation of Nrf2‐dependent HO‐1 expression and reductions in ROS and TNF‐α generation via the activation of Erk1/2 and PI3K/Akt in EA.hy926 cells. HO‐1 may thus be an important potential target for further research into the cytoprotective actions of halophenols.
Privacy Preserved Self-Awareness on the Community via Crowd Sensing
Authors: Fan Huiting , Xing Kai , Tan Lei , Rui Weikang , Xu Zhonghu , Zhang Shuo , Xu Jing
Published: June 2017

In social activities, people are interested in some statistical data, such as purchase records, monthly consumption, and health data, which are usually utilized in recommendation systems. And it is seductive for them to acquire the ranking of these data among friends or other communities. In the meantime, they want their privacy data to be confidential. Therefore, a strategy is presented to allow users to obtain the result of calculating their privacy data while preserving these data. In this method, firstly a polynomial approximation function model is set up for each user. Afterwards, “fragment” the coefficients of each model into pieces. Eventually “blend” all scraps to build the global model of all users. Users can use the global model to gain their corresponding ranking results after a special computing. Security analyses of three aspects elaborate the validity of proposed privacy method, even if some spiteful attackers try to steal private data of users, no matter who they are (users or someone outside the community). Experiments results manifest that the global model competently fits all users data and all privacy data are protected.
Study of Train-Side Passive Magnetic Measurements with Applications to Train Localization
Authors: Heirich Oliver , Siebler Benjamin , Hedberg Erik
Published: June 2017

Passive magnetic sensors measure the magnetic field density in three axes and are often integrated on a single chip. These low-cost sensors are widely used in car navigation as well as in battery powered navigation equipment such as smartphones as part of an electronic compass. We focus on a train localization application with multiple, exclusively onboard sensors and a track map. This approach is considered as a base technology for future railway applications such as collision avoidance systems or autonomous train driving. In this paper, we address the following question: how beneficial are passive magnetic measurements for train localization? We present and analyze measurements of two different magnetometers recorded on a regional train at regular passenger service. We show promising correlations of the measurements with the track positions and the traveled switch way. The processed data reveals that the railway environment has repeatable, location-dependent magnetic signatures. This is considered as a novel approach to train localization, as the use of these magnetic signals at first view is not obvious. The proposed methods based on passive magnetic measurements show a high potential to be integrated in new and existing train localization approaches.
Update on Diagnosis and Treatment of Diabetic Retinopathy: A Consensus Guideline of the Working Group of Ocular Health (Spanish Society of Diabetes and Spanish Vitreous and Retina Society)
Authors: Corcóstegui Borja , Durán Santiago , González-Albarrán María Olga , Hernández Cristina , Ruiz-Moreno José María , Salvador Javier , Udaondo Patricia , Simó Rafael
Published: June 2017

A group of members of the Spanish Retina and Vitreous Society (SERV) and of the Working Group of Ocular Health of the Spanish Society of Diabetes (SED) updated knowledge regarding the diagnosis and treatment of diabetic retinopathy (DR) based on recent evidence reported in the literature. A synthesis of this consensus forms the basis of the present review, which is intended to inform clinicians on current advances in the field of DR and their clinical applicability to patients with this disease. Aspects presented in this article include screening procedures of DR, new technologies in the early diagnosis of DR, control of risk factors in the different stages of the disease, indications of panretinal laser photocoagulation, efficacy of intravitreal antiangiogenic agents and steroids, and surgical options for treating DR-related complications. Practical information regarding periodicity of screening procedures in patients with type 1 and type 2 diabetes, ophthalmological controls according to the stage of retinopathy and complications, and criteria and degree of urgency for referral of a DR patient to the ophthalmologist are also presented.
Physical Trauma among Refugees: Comparison between Refugees and Local Population Who Were Admitted to Emergency Department—Experience of a State Hospital in Syrian Border District
Authors: Duzkoylu Yigit , Basceken Salim Ilksen , Kesilmez Emrullah Cem
Published: June 2017

Background. Hundreds of thousands of people have fled to Turkey since the civil war started in Syria in 2011. Refugees and local residents have been facing various challenges such as sociocultural and economic ones and access to health services. Trauma exposure is one of the most important and underestimated health problems of refugees settling in camps. Aims. We aimed to evaluate refugee admissions to emergency department because of trauma in means of demographics of patients and mechanism of trauma and compare the results with the local population. Methods. Retrospective evaluation of results and comparison with the results of local population. Results. We determined that the ratio of emergency admission of refugee patients because of trauma was significantly higher than the local population for most types of trauma. Conclusion. Further studies with more refugee participants are needed to fully understand the underlying reasons for this high ratio to protect refugees as well as for planning to take caution to attenuate the burden on healthcare systems.
A Study of Charged Cylindrical Gravitational Collapse with Dissipative Fluid
Authors: Chakraborty Sanjukta , Chakraborty Subenoy
Published: June 2017

The present works deals with gravitational collapse of cylindrical viscous heat conducting anisotropic fluid following the work of Misner and Sharp. Using Darmois matching conditions, the dynamical equations are derived and the effects of charge and dissipative quantities over the cylindrical collapse are analyzed. Finally, using the Miller-Israel-Steward causal thermodynamic theory, the transport equation for heat flux is derived and its influence on collapsing system has been studied.
Present Status of Ganges River DolphinsPlatanista gangetica gangetica(Roxburgh, 1801) in the Turag River, Dhaka, Bangladesh
Authors: Baki Mohammad Abdul , Bhouiyan Naser Ahmed , Islam Md. Saiful , Alam Shayer Mahmood Ibney , Shil Shibananda , Hossain Md. Muzammel
Published: June 2017

Freshwater ecosystem degradation in the Turag River basin is increasing due to rising human settlement, reduced water flow during the dry season, new large land development projects, and toxic emissions caused by brick kilns. The population of river dolphins was estimated through surveys carried out from December 2012 to November 2013. Surveys were conducted on a fortnightly basis. The dolphins were counted within an 18.4 km stretch (known to be the most polluted stretch) of the 75 km long river. A total of 62 dolphin sightings were recorded, both as individual sightings and as groups. The highest monthly count was in August. The best-high-low estimates of 9-11-7 individuals were recorded in August 2013 in river ecology. Seasonal changes in spatial distribution were observed. The survey revealed that rising floodwater stimulated an increase in the dolphin population in the study area from July to October. The maximum encounter rate was also 0.49 sightings km−1for the month of August. The sightings and encounter rates of dolphins were lower from December to July (dry and premonsoon period) likely due to reduced water flow and adverse water quality of this river.
Modeling and Analysis of Truck Mounted Concrete Pump Boom by Virtual Prototyping
Authors: Ren Wu , Li Zhongwei , Bi Yanping , Zhao Shan , Peng Bo , Zhou Liming
Published: June 2017

By far there is lack of research on different working conditions between rigid and flexible dynamics of truck mounted concrete pump booms. First a 3D model has been established by using virtual prototyping technology of a 37 m long boom in Pro/Engineering software. Then the rigid body simulation model has been built. Next modal superimposition method is adopted to change the 4 rigid body booms into flexible ones. Kinematics law and dynamic characteristics of 4 common working conditions had been studied then. Next tip displacement and the first boom hydraulic cylinder force of the 4 working conditions between rigid and flexible models have been researched. Furthermore the first natural frequencies of the structure have been calculated. The results show that the frequency of the horizontal condition has the lowest of all and the roof condition has the largest of all. Besides the cylinder forces of the flexible model are larger than the corresponding rigid ones because of the flexible boom vibration. Finally an experiment has been done on a boom test rig which proved that the established simulation model is reasonable and the frequency results are correct. All of these provide design reference to mechanical manipulator as well as reducing product development cost of such mechanism.
Autocrine BMP-4 Signaling Is a Therapeutic Target in Colorectal Cancer
Authors: Yokoyama Yuichiro , Watanabe Toshiaki , Tamura Yusuke , Hashizume Yoshinobu , Miyazono Kohei , Ehata Shogo
Published: June 2017

Poor prognoses for colorectal cancer patients with metastatic lesions have driven demand for the development of novel targeted therapies. Here, we demonstrate that expression of bone morphogenetic protein 4 (BMP-4) is universally upregulated in human colorectal cancer cells and tissues, resulting in activated BMP signaling. Inhibition of endogenous BMP signaling by the BMP type I receptor inhibitor LDN-193189 elevated expression of the phosphatase DUSP5 in colorectal cancer cells, inducing apoptosis via dephosphorylation of Erk MAPK. Administering LDN-193189 to mice diminished tumor formation of colorectal cancer cells. Our findings suggest inhibition of autocrine BMP-4 as a candidate treatment strategy for colorectal cancer. Cancer Res; 77(15); 4026–38. ©2017 AACR.
Treatment of Pancreatic Cancer Patient–Derived Xenograft Panel with Metabolic Inhibitors Reveals Efficacy of Phenformin
Authors: Rajeshkumar N.V. , Yabuuchi Shinichi , Pai Shweta G. , De Oliveira Elizabeth , Kamphorst Jurre J. , Rabinowitz Joshua D. , Tejero Héctor , Al-Shahrour Fátima , Hidalgo Manuel , Maitra Anirban , Dang Chi V.
Published: June 2017

Purpose: To identify effective metabolic inhibitors to suppress the aggressive growth of pancreatic ductal adenocarcinoma (PDAC), we explored the in vivo antitumor efficacy of metabolic inhibitors, as single agents, in a panel of patient-derived PDAC xenograft models (PDX) and investigated whether genomic alterations of tumors correlate with the sensitivity to metabolic inhibitors.

Experimental Design: Mice with established PDAC tumors from 6 to 13 individual PDXs were randomized and treated, once daily for 4 weeks, with either sterile PBS (vehicle) or the glutaminase inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES), transaminase inhibitor aminooxyacetate (AOA), pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA), autophagy inhibitor chloroquine (CQ), and mitochondrial complex I inhibitor phenformin/metformin.

Results: Among the agents tested, phenformin showed significant tumor growth inhibition (>30% compared with vehicle) in 5 of 12 individual PDXs. Metformin, at a fivefold higher dose, displayed significant tumor growth inhibition in 3 of 12 PDXs similar to BPTES (2/8 PDXs) and DCA (2/6 PDXs). AOA and CQ had the lowest response rates. Gene set enrichment analysis conducted using the baseline gene expression profile of pancreatic tumors identified a gene expression signature that inversely correlated with phenformin sensitivity, which is in agreement with the phenformin gene expression signature of NIH Library of Integrated Network-based Cellular Signatures (LINCS). The PDXs that were more sensitive to phenformin showed a baseline reduction in amino acids and elevation in oxidized glutathione. There was no correlation between phenformin response and genetic alterations in KRAS, TP53, SMAD4, or PTEN.

Conclusions: Phenformin treatment showed relatively higher antitumor efficacy against established PDAC tumors, compared with the efficacy of other metabolic inhibitors and metformin. Phenformin treatment significantly diminished PDAC tumor progression and prolonged tumor doubling time. Overall, our results serve as a foundation for further evaluation of phenformin as a therapeutic agent in pancreatic cancer. Clin Cancer Res; 23(18); 5639–47. ©2017 AACR.
Wnt/β-catenin Signaling Contributes to Tumor Malignancy and Is Targetable in Gastrointestinal Stromal Tumor
Authors: Zeng Shan , Seifert Adrian M. , Zhang Jennifer Q. , Cavnar Michael J. , Kim Teresa S. , Balachandran Vinod P. , Santamaria-Barria Juan A. , Cohen Noah A. , Beckman Michael J. , Medina Benjamin D. , Rossi Ferdinand , Crawley Megan H. , Loo Jennifer K. , Maltbaek Joanna H. , Besmer Peter , Antonescu Cristina R. , DeMatteo Ronald P.
Published: June 2017

Gastrointestinal stromal tumor (GIST) is the most common type of sarcoma and usually harbors either a KIT or PDGFRA mutation. However, the molecular basis for tumor malignancy is not well defined. Although the Wnt/β-catenin signaling pathway is important in a variety of cancers, its role in GIST is uncertain. Through analysis of nearly 150 human GIST specimens, we found that some human GISTs expressed β-catenin and contained active, dephosphorylated nuclear β-catenin. Furthermore, advanced human GISTs expressed reduced levels of the Wnt antagonist DKK4. Accordingly, in human GIST T1 cells, Wnt stimulation increased β-catenin–mediated transcriptional activity in a reporter assay as well as transcription of the downstream target genes Axin2 and CCND1. In contrast, DKK4 overexpression in GIST T1 cells reduced Wnt/β-catenin signaling. In addition, we showed that nuclear β-catenin stability was partially regulated by the E3 ligase COP1, as demonstrated with coimmunoprecipitation and COP1 knockdown. Three molecular inhibitors of the Wnt/β-catenin pathway demonstrated antitumor efficacy in various GIST models, both in vitro and in vivo. Notably, the tankyrase inhibitor G007-LK alone had substantial activity against tumors of genetically engineered KitV558Δ/+ mice, and the effect was increased by the addition of the Kit inhibitor imatinib mesylate. Collectively, our findings demonstrate that Wnt/β-catenin signaling is a novel therapeutic target for selected untreated or imatinib-resistant GISTs. Mol Cancer Ther; 16(9); 1954–66. ©2017 AACR.
Cisplatin Increases Sensitivity to FGFR Inhibition in Patient-Derived Xenograft Models of Lung Squamous Cell Carcinoma
Authors: Weeden Clare E. , Holik Aliaksei Z. , Young Richard J. , Ma Stephen B. , Garnier Jean-Marc , Fox Stephen B. , Antippa Phillip , Irving Louis B. , Steinfort Daniel P. , Wright Gavin M. , Russell Prudence A. , Ritchie Matthew E. , Burns Christopher J. , Solomon Benjamin , Asselin-Labat Marie-Liesse
Published: June 2017

Lung squamous cell carcinoma (SqCC) is a molecularly complex and genomically unstable disease. No targeted therapy is currently approved for lung SqCC, although potential oncogenic drivers of SqCC have been identified, including amplification of the fibroblast growth factor receptor 1 (FGFR1). Reports from a recently completed clinical trial indicate low response rates in patients treated with FGFR tyrosine kinase inhibitors, suggesting inadequacy of FGFR1 amplification as a biomarker of response, or the need for combination treatment. We aimed to develop accurate models of lung SqCC and determine improved targeted therapies for these tumors. We show that detection of FGFR1 mRNA by RNA in situ hybridization is a better predictor of response to FGFR inhibition than FGFR1 gene amplification using clinically relevant patient-derived xenograft (PDX) models of lung SqCC. FGFR1-overexpressing tumors were observed in all histologic subtypes of non–small cell lung cancers (NSCLC) as assessed on a tissue microarray, indicating a broader range of tumors that may respond to FGFR inhibitors. In FGFR1-overexpressing PDX tumors, we observed increased differentiation and reduced proliferation following FGFR inhibition. Combination therapy with cisplatin was able to increase tumor cell death, and dramatically prolonged animal survival compared to single-agent treatment. Our data suggest that FGFR tyrosine kinase inhibitors can benefit NSCLC patients with FGFR1-overexpressing tumors and provides a rationale for clinical trials combining cisplatin with FGFR inhibitors. Mol Cancer Ther; 16(8); 1610–22. ©2017 AACR.
Intermittent Dosing with Sulindac Provides Effective Colorectal Cancer Chemoprevention in the Azoxymethane-Treated Mouse Model
Authors: Chandra Swati , Nymeyer Ariel C. , Rice Photini Faith , Gerner Eugene W. , Barton Jennifer K.
Published: June 2017

Sulindac is an NSAID that can provide effective chemoprevention for colorectal cancer. In this study, alternative dosing regimens of sulindac were evaluated for their chemoprevention effectiveness in the azoxymethane-treated A/J mouse model of colorectal cancer. High-resolution endoscopic optical coherence tomography was utilized to time-serially measure tumor number and tumor burden in the distal colon as the biological endpoints. Four treatment groups were studied: (i) daily for 20 weeks (sulindac-daily); (ii) for 2 weeks, then no sulindac for 2 weeks, cycle repeated 5 times (sulindac-2); (iii) for 10 weeks (“on”), then no sulindac for 10 weeks (“off”; sulindac-10); and (iv) no sulindac (sulindac-none). Sulindac-2 and sulindac-daily had statistically significantly lower final tumor counts and slopes (change in number of tumors per week) when compared with sulindac-none (P < 0.0001). All of the treatment groups had statistically significantly lower final tumor burdens and slopes when compared with sulindac-none (P < 0.001). There was a prolonged latency period in the sulindac-10 group, with no significant difference between the “off” portion of this treatment and sulindac-none. These results suggest that, although daily doses of sulindac provide the most optimal effects, intermittent doses of sulindac in a 50% duty cycle with an overall 4-week period (sulindac-2 model) can provide highly effective chemoprevention of colorectal cancer in this model. After cessation of sulindac treatment (sulindac-10 “off”), there is no evidence of either a persistent chemopreventive effect or a rebound effect. Cancer Prev Res; 10(8); 459–66. ©2017 AACR.
Expression of TLR2, NOD1, and NOD2 and the NLRP3 Inflammasome in Renal Tubular Epithelial Cells of Male versus Female Mice
Authors: DeWolf Sean E. , Shigeoka Alana A. , Scheinok Andrew , Kasimsetty Sashi G. , Welch Alexander K. , McKay Dianne B.
Published: June 2017

Background: Gender-biased outcomes are associated with acute kidney injury (AKI) and human and animal studies have shown that females are preferentially protected from renal ischemia. However, the reason for this is not known. One clue might lie with pattern recognition receptors (PRRs), which are triggers of ischemic injury when ligated by molecules in the ischemic milieu. Several PRR families are expressed by renal tubular epithelial cells (RTEs) and incite cell death signaling and production of pro-inflammatory molecules. Blockade of specific PRRs (e.g., TLR2, NOD1, NOD2, and NLRP3) provides highly significant protection from ischemic RTE injury. As a first step to understand gender-biased outcomes of AKI, we tested whether constitutive gender-based differences exist in expression of these PRRS in RTEs. Methods: To determine whether PRR expression differences exist, primary RTEs isolated from male and female WT kidneys were examined by FACS, qPCR, and Western Blot for expression of TLR2, NOD1, NOD2, and NLRP3 inflammasome components. Results: No RTE gender-based differences in TLR2, NOD1, NOD2, NLRP3, or ASC were found. RTEs from female kidneys had approximately half the mRNA, but the same protein concentration of pro-caspase-1 compared to RTEs isolated from male kidneys. Conclusions: Our findings indicate that intrinsic gender differences in RTE expression of TLR2, NOD1, NOD2, NLRP3, and ASC are not responsible for the gender-biased outcomes observed in ischemia/reperfusion injury. The lower caspase-1 mRNA expression in RTEs from females warrants further exploration of additional upstream signals that might differentially regulate caspase-1 in male vs. female RTEs.
Shifting Focus: From Hydration for Performance to Hydration for Health
Authors: Perrier Erica T.
Published: June 2017

Over the past 10 years, literature on hydration biomarkers has evolved considerably - from (de)hydration assessment towards a more global definition of biomarkers of hydration in daily life. This shift in thinking about hydration markers was largely driven by investigating the differences that existed between otherwise healthy individuals whose habitual, ad-libitum drinking habits differ, and by identifying physiological changes in low-volume drinkers who subsequently increase their water intake. Aside from obvious differences in urinary volume and concentration, a growing body of evidence is emerging that links differences in fluid intake with small, but biologically significant, differences in vasopressin (copeptin), glomerular filtration rate, and markers of metabolic dysfunction or disease. Taken together, these pieces of the puzzle begin to form a picture of how much water intake should be considered adequate for health, and represent a shifting focus from hydration for performance, toward hydration for health outcomes. This narrative review outlines the key areas of research in which the global hydration process - including water intake, urinary hydration markers, and vasopressin - has been associated with health outcomes, focusing on kidney and metabolic endpoints. It will also provide a commentary on how various hydration biomarkers may be used in hydration for health assessment. Finally, if adequate water intake can play a role in maintaining health, how might we tell if we are drinking enough? Urine output is easily measured, and can take into account differences in daily physical activity, climate, dietary solute load, and other factors that influence daily water needs. Today, targets have been proposed for urine osmolality, specific gravity, and color that may be used by researchers, clinicians, and individuals as simple indicators of optimal hydration. However, there remain a large number of incomplete or unanswered research questions regarding the relationships between water intake, hydration, vasopressin, and health outcomes. Thus, this emerging field represents an excellent opportunity, particularly for young researchers, to develop relevant and novel lines of research.
Monitoring Body Water Balance in Pregnant and Nursing Women: The Validity of Urine Color
Authors: McKenzie Amy L. , Armstrong Lawrence E.
Published: June 2017

Background: Urine osmolality (UOSM) reflects the renal regulation of excess fluid or deficit fluid, and therefore, serves as a marker of hydration status. Little is known about monitoring hydration in pregnant and lactating women despite significant physiological challenges to body water balance during that time. Therefore, we designed a study to assess if urine color (UCOL), an inexpensive and practical method, was a valid means of assessing urine concentration. Twenty-four hour UCOL was significantly correlated with 24 h UOSM in all women: pregnant, lactating, and control (r = 0.61-0.84, all p < 0.001). Utilizing a receiver operating characteristic statistical analysis, we found that 24 h and single sample UCOL had excellent diagnostic accuracy for identifying UOSM ≥500 mOsm·kg-1 in all women (area under the curve = 0.68-0.95, p < 0.001-0.46), and the UCOL that reflected this cut off was ≥4 on the UCOL chart. Summary: Therefore, UCOL is a valid marker of urine concentration and ultimately hydration status in pregnant, lactating, and non-pregnant, non-lactating women. For pregnant, lactating, and control women, the UCOL chart is a valid tool that can be used to monitor urine concentration in a single sample or over the course of the day via a 24 h sample. Key Message: Women who present with a UCOL of 4 or more likely have a UOSM ≥500 mOsm·kg-1. Given the positive health benefits associated with UOSM <500 mOsm·kg-1, women should aim for a 1, 2, or 3 on the UCOL chart. If a UCOL of ≥4 is observed, women should consider increasing fluid consumption to improve hydration status.
Osteoprotegerin Is the Strongest Predictor for Progression of Arterial Calcification in Peritoneal Dialysis Patients
Authors: Avila Marcela , Mora Carmen , Prado María del Carmen , Zavala Miriam , Paniagua Ramón ,   Mexican Collaborative Group
Published: June 2017

Background: Arterial calcification (AC) is frequent in patients with end stage renal disease and is also considered a risk factor for later morbidity and mortality. However, long-term factors associated with the process are not well known. We analyzed the trends over time of biomarkers related with development and progression of AC in incident patients on peritoneal dialysis (PD). Methods: We performed a prospective study with 186 patients on PD followed up for 1 year. We analyzed the progression of AC in the abdominal aorta and pelvic vessels by calcification score (CaSc), using16-cut computerized multidetector tomography at baseline and 1 year. Variables related with PD treatment, inflammation, and mineral metabolism were measured at baseline, 6, and 12 months of follow-up. Changes in biochemical variables were analyzed for their relationship with changes in AC. Results: Over 1 year, the number of patients with AC increased from 47 to 56%, and CaSc from 355 (interquartile range [IQR] 75-792) to 529 (IQR 185-1632). A total of 43.5% of patients remained free of calcification, 11.7% had new calcifications, and 44.8% had progression of calcification. Older age, diabetes, high systolic blood pressure, body mass index, cholesterol, and osteoprotegerin (OPG), as well as lower levels of albumin, serum creatinine, and osteocalcin, were associated with development of new, and rapid progression of, calcification. In multivariate logistic analysis, OPG remained the most significant (OR 1.27, 95% CI 1.11-1.47, p < 0.001). Conclusion: OPG was the strongest risk factor associated with new development and rapid progression of AC in incident PD patients.
Adult Ventricular Myocytes Segregate KCNQ1 and KCNE1 to Keep the
I
Ks
Amplitude in Check Until When Larger
I
Ks
Is Needed
Authors: Jiang Min , Wang Yuhong , Tseng Gea-Ny
Published: June 2017

Background—

KCNQ1 and KCNE1 assemble to form the slow delayed rectifier (
I
Ks
) channel critical for shortening ventricular action potentials during high β-adrenergic tone. However, too much
I
Ks
under basal conditions poses an arrhythmogenic risk. Our objective is to understand how adult ventricular myocytes regulate the
I
Ks
amplitudes under basal conditions and in response to stress.

Methods and Results—

We express fluorescently tagged KCNQ1 and KCNE1 in adult ventricular myocytes and follow their biogenesis and trafficking paths. We also study the distribution patterns of native KCNQ1 and KCNE1, and their relationship to
I
Ks
amplitudes, in chronically stressed ventricular myocytes, and use COS-7 cell expression to probe the underlying mechanism. We show that KCNQ1 and KCNE1 are both translated in the perinuclear region but traffic by different routes, independent of each other, to their separate subcellular locations. KCNQ1 mainly resides in the jSR (junctional sarcoplasmic reticulum), whereas KCNE1 resides on the cell surface. Under basal conditions, only a small portion of KCNQ1 reaches the cell surface to support the
I
Ks
function. However, in response to chronic stress, KCNQ1 traffics from jSR to the cell surface to boost the
I
Ks
amplitude in a process depending on Ca binding to CaM (calmodulin).

Conclusions—

In adult ventricular myocytes, KCNE1 maintains a stable presence on the cell surface, whereas KCNQ1 is dynamic in its localization. KCNQ1 is largely in an intracellular reservoir under basal conditions but can traffic to the cell surface and boost the
I
Ks
amplitude in response to stress.
Patient-Reported Health-Related Quality of Life Is a Predictor of Outcomes in Ambulatory Heart Failure Patients Treated With Left Ventricular Assist Device Compared With Medical Management
Authors: Stehlik Josef , Estep Jerry D. , Selzman Craig H. , Rogers Joseph G. , Spertus John A. , Shah Keyur B. , Chuang Joyce , Farrar David J. , Starling Randall C.
Published: June 2017

Background—

The prospective observational ROADMAP study (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management) demonstrated that ambulatory advanced heart failure patients selected for left ventricular assist device (LVAD) were more likely to be alive at 1 year on original therapy with ≥75-m improvement in 6-minute walk distance compared with patients assigned to optimal medical management. Whether baseline health-related quality of life (hrQoL) resulted in a heterogeneity of this treatment benefit is unknown.

Methods and Results—

Patient-reported hrQoL was assessed with EuroQol questionnaire and visual analogue scale (VAS). We aimed to identify predictors of event-free survival and survival with acceptable hrQoL (VAS≥60). LVAD patients had significant improvement in 3 of 5 EuroQol dimensions (
P
<0.05), but no significant changes were observed with optimal medical management. Among patients with baseline VAS<55, survival on original treatment was lower for optimal medical management patients compared with those assigned to LVAD (58±7% versus 82±5%;
P
=0.004). No such difference was seen if baseline VAS was ≥55 (70±7% versus 75±9%;
P
=0.79). Survival on original therapy with acceptable quality of life was also more likely with LVAD versus optimal medical management if baseline VAS was <55, whereas outcomes in patients with higher baseline VAS scores were similar regardless of treatment assignment (
P
=0.046 for treatment arm and baseline VAS interaction).

Conclusions—

LVAD therapy resulted in improvement of patient health status in heart failure patients with low self-reported hrQoL, but not in patients with acceptable quality of life at the time of LVAD implantation. Patient-reported hrQoL should be integrated into decision making concerning the use and timing of LVAD therapy in heart failure patients who are symptom limited but remain ambulatory.

Clinical Trial Registration—

URL:
http://www.ClinicalTrials.gov
. Unique identifier: NCT01452802.
Learning a Comorbidity-Driven Taxonomy of Pediatric Pulmonary Hypertension
Authors: Ong Mei-Sing , Mullen Mary P. , Austin Eric D. , Szolovits Peter , Natter Marc D. , Geva Alon , Cai Tianxi , Kong Sek Won , Mandl Kenneth D.
Published: June 2017

Rationale:

Pediatric pulmonary hypertension (PH) is a heterogeneous condition with varying natural history and therapeutic response. Precise classification of PH subtypes is, therefore, crucial for individualizing care. However, gaps remain in our understanding of the spectrum of PH in children.

Objective:

We seek to study the manifestations of PH in children and to assess the feasibility of applying a network-based approach to discern disease subtypes from comorbidity data recorded in longitudinal data sets.

Methods and Results:

A retrospective cohort study comprising 6 943 263 children (<18 years of age) enrolled in a commercial health insurance plan in the United States, between January 2010 and May 2013. A total of 1583 (0.02%) children met the criteria for PH. We identified comorbidities significantly associated with PH compared with the general population of children without PH. A Bayesian comorbidity network was constructed to model the interdependencies of these comorbidities, and network-clustering analysis was applied to derive disease subtypes comprising subgraphs of highly connected comorbid conditions. A total of 186 comorbidities were found to be significantly associated with PH. Network analysis of comorbidity patterns captured most of the major PH subtypes with known pathological basis defined by the World Health Organization and Panama classifications. The analysis further identified many subtypes documented in only a few case studies, including rare subtypes associated with several well-described genetic syndromes.

Conclusions:

Application of network science to model comorbidity patterns recorded in longitudinal data sets can facilitate the discovery of disease subtypes. Our analysis relearned established subtypes, thus validating the approach, and identified rare subtypes that are difficult to discern through clinical observations, providing impetus for deeper investigation of the disease subtypes that will enrich current disease classifications.
Inhibition of MicroRNA-146a and Overexpression of Its Target Dihydrolipoyl Succinyltransferase Protect Against Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction
Authors: Heggermont Ward A. , Papageorgiou Anna-Pia , Quaegebeur Annelies , Deckx Sophie , Carai Paolo , Verhesen Wouter , Eelen Guy , Schoors Sandra , van Leeuwen Rick , Alekseev Sergey , Elzenaar Ies , Vinckier Stefan , Pokreisz Peter , Walravens Ann-Sophie , Gijsbers Rik , Van Den Haute Chris , Nickel Alexander , Schroen Blanche , van Bilsen Marc , Janssens Stefan , Maack Christoph , Pinto Yigal , Carmeliet Peter , Heymans Stephane
Published: June 2017

Background:

Cardiovascular diseases remain the predominant cause of death worldwide, with the prevalence of heart failure continuing to increase. Despite increased knowledge of the metabolic alterations that occur in heart failure, novel therapies to treat the observed metabolic disturbances are still lacking.

Methods:

Mice were subjected to pressure overload by means of angiotensin-II infusion or transversal aortic constriction. MicroRNA-146a was either genetically or pharmacologically knocked out or genetically overexpressed in cardiomyocytes. Furthermore, overexpression of dihydrolipoyl succinyltransferase (DLST) in the murine heart was performed by means of an adeno-associated virus.

Results:

MicroRNA-146a was upregulated in whole heart tissue in multiple murine pressure overload models. Also, microRNA-146a levels were moderately increased in left ventricular biopsies of patients with aortic stenosis. Overexpression of microRNA-146a in cardiomyocytes provoked cardiac hypertrophy and left ventricular dysfunction in vivo, whereas genetic knockdown or pharmacological blockade of microRNA-146a blunted the hypertrophic response and attenuated cardiac dysfunction in vivo. Mechanistically, microRNA-146a reduced its target DLST—the E2 subcomponent of the α-ketoglutarate dehydrogenase complex, a rate-controlling tricarboxylic acid cycle enzyme. DLST protein levels significantly decreased on pressure overload in wild-type mice, paralleling a decreased oxidative metabolism, whereas DLST protein levels and hence oxidative metabolism were partially maintained in microRNA-146a knockout mice. Moreover, overexpression of DLST in wild-type mice protected against cardiac hypertrophy and dysfunction in vivo.

Conclusions:

Altogether we show that the microRNA-146a and its target DLST are important metabolic players in left ventricular dysfunction.
Federalism, Paradiplomacy and Foreign Policy: A Case of Mutual Neglect
Authors: Lequesne Christian , Paquin Stéphane
Published: June 2017

Paradiplomacy, federalism and international negotiation are increasingly prevalent phenomena that require more theoretical attention. Successful mobilization of non-central governments has increased their relevance on the international stage. The rise of paradiplomacy complicates conditions for both international negotiation and the formulation of foreign policy in federal regimes. Westphalian state diplomacy is finding it increasingly difficult to cope with the proliferation of ad hoc and informal arrangements that bind non-central governments. The international arena is inhabited by an ever larger number of players that sometimes have significant autonomy from the central state.
A new species of Amaurobius C.L. Koch, 1837 (Araneae: Amaurobiidae) from Apennine Mountains (Italy) with the description of the male of A. pavesii Pesarini, 1991
Authors: BALLARIN FRANCESCO , PANTINI PAOLO
Published: June 2017

A new species of the genus Amaurobius C.L. Koch, 1837, Amaurobius pesarinii sp. n., from the Apennine Mountains (Italy) is described on the basis of both sexes. The male of A. pavesii Pesarini, 1991, previously unknown, is also described. Females of A. pavesii and both sexes of the similar A. scopolii Thorell, 1871 are re-described. Detailed description of morphological characters allow clear separation between these species and the closely related A. ferox (Walckenaer, 1820). Their phylogenetic relationships among the most common Italian Amaurobius species are discussed on the basis of molecular data (partial fragments of the genes COI, 16S and H3), together with their distribution across the Italian Peninsula. This is the first contribution to a multi-locus phylogenetic tree of European Amaurobius species. The synonymy of A. sciakyi Pesarini, 1991 with A. ruffoi Thaler, 1990 is proposed based on morphological characters.
A comprehensive and integrative re-description of Synchaeta tremula (Müller, 1786) and the newly rediscovered Synchaeta tremuloida Pourriot, 1965 (Rotifera: Synchaetidae)
Authors: WILKE TANJA , AHLRICHS WILKO H. , BININDA-EMONDS OLAF R.P.
Published: June 2017

In this paper, we focus on the two morphologically similar species Synchaeta tremula (Müller, 1786) and Synchaeta tremuloida Pourriot, 1965. This study records one of the first detections of the latter species since its initial description and clarifies its uncertain taxonomic status. Using an integrative approach combining morphological data (from light and scanning electron microscopy) with molecular and ecological data, we present re-descriptions of S. tremula and S. tremuloida and confirm their status as separate species. Finally, we also provide a unique character set that can be readily applied to unambiguously identify each species using easily observable features.
Stalking Victimization Among College Students: The Role of Disability Within a Lifestyle-Routine Activity Framework
Authors: Reyns Bradford W. , Scherer Heidi
Published: June 2017

This study utilized the routine activity perspective and incorporated measures of disability to examine the underexplored relationship between disability status and stalking victimization. Survey data from approximately 43,000 college students from across the United States were examined to explore these relationships. Results indicated that disability was a significant risk factor for victimization. Consistent with theoretical expectations, several measures of lifestyles and routine activities also were found to increase risk of stalking victimization, including volunteering, employment, and risk-taking behaviors such as alcohol and drug use. Collectively, the results suggest that measures of disability should be incorporated into future research testing the routine activities perspective for interpersonal victimization.
Challenges of Political Development in Afghanistan: Mass, Elite and Institutional Dimensions
Authors: Maley William
Published: June 2017

The transition in Afghanistan is manifestly beset by multiple challenges, yet behind obvious issues such as insecurity and corruption lie a range of deeper problems related to the way in which the Afghan political system has developed. Trust deficits, real conflicts of interest, and parallel and potentially conflicting systems of authority, have affected both the mass population—many of whom feel disconnected and disenfranchised—and political elites, which remain severely divided. The combination of a presidential system with a highly centralized formal state structure had fostered patrimonialism at the expense of institutional development. Unless and until these problems are addressed, the likelihood that any Afghan government will be able to take the lead in confronting the country’s problems remains low.
Enhancing Accessibility for Students With Decoding Difficulties on Large-Scale Reading Assessments
Authors: Gandhi Allison Gruner , Ogut Burhan , Stein Laura , Bzura Robin , Danielson Louis
Published: June 2017

This study reports findings from studies examining potential read-aloud accommodations on standardized reading comprehension assessments for students with decoding difficulties. Three types of accommodations were evaluated: question stems and answer options read aloud; question stems, answer options, and proper nouns read aloud; and full read-aloud. Drawing from a sample of 207 fourth-grade students with and without decoding difficulties, we used 3-level hierarchical linear modeling to assess whether there were significant differences between students with and without decoding difficulties in the effect of each accommodation relative to no accommodation. Analyses showed that, for the students with decoding difficulties, all 3 read-aloud accommodations had significant effects when compared with no accommodation at all, and these effects were significantly larger than for average readers (effect sizes: 0.49, 0.55, and 0.50, respectively). When non–individualized education program students were excluded from the group of students with decoding difficulties, the effect sizes became notably larger.