bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relaxin‐3 innervation of the intergeniculate leaflet of the rat thalamus – neuronal tract‐tracing and in vitro electrophysiological studies
Authors: Blasiak Anna , Blasiak Tomasz , Lewandowski Marian H. , Hossain Mohammed Akhter , Wade John D. , Gundlach Andrew L. 
Published: February 2013

AbstractBehavioural state is controlled by a range of neural systems that are sensitive to internal and external stimuli. The relaxin‐3 and relaxin family peptide receptor 3 (RXFP3) system has emerged as a putative ascending arousal network with putative involvement in regulation of stress responses, neuroendocrine control, feeding and metabolism, circadian activity and cognition. Relaxin‐3/γ‐aminobutyric acid neuron populations have been identified in the nucleus incertus, pontine raphe nucleus, periaqueductal grey (PAG) and an area dorsal to the substantia nigra. Relaxin‐3‐positive fibres/terminals densely innervate arousal‐related structures in the brainstem, hypothalamus and limbic forebrain, but the functional significance of the heterogeneous relaxin‐3 neuron distribution and its inputs to specific brain areas are unclear. Therefore, in this study, we used neuronal tract‐tracing and immunofluorescence staining to explore the source of the dense relaxin‐3 innervation of the intergeniculate leaflet (IGL) of the thalamus, a component of the neural circadian timing system. Confocal microscopy analysis revealed that relaxin‐3‐positive neurons retrogradely labelled from the IGL were predominantly present in the PAG and these neurons expressed corticotropin‐releasing factor receptor‐like immunoreactivity. Subsequently, whole‐cell patch‐clamp recordings revealed heterogeneous effects of RXFP3 activation in the IGL by the RXFP3 agonist, relaxin‐3 B‐chain/insulin‐like peptide‐5 A‐chain (R3/I5). Identified, neuropeptide Y‐positive IGL neurons, known to influence suprachiasmatic nucleus activity, were excited by R3/I5, whereas neurons of unidentified neurotransmitter content were either depolarized or displayed a decrease in action potential firing and/or membrane potential hyperpolarization. Our data identify a PAG to IGL relaxin‐3/RXFP3 pathway that might convey stress‐related information to key elements of the circadian system and influence behavioural state rhythmicity.
Structure of the extracellular domains of human and Xenopus Fn14: implications in the evolution of TWEAK and Fn14 interactions
Authors: Pellegrini Maria , Willen Laure , Perroud Mai , Krushinskie Dennis , Strauch Kathy , Cuervo Hernan , Day Eric S. , Schneider Pascal , Zheng Timothy S. 
Published: February 2013

TWEAK (TNF homologue with weak apoptosis‐inducing activity) and Fn14 (fibroblast growth factor‐inducible protein 14) are members of the tumor necrosis factor (TNF) ligand and receptor super‐families. Having observed that Xenopus Fn14 cross‐reacts with human TWEAK, despite its relatively low sequence homology to human Fn14, we examined the conservation in tertiary fold and binding interfaces between the two species. Our results, combining NMR solution structure determination, binding assays, extensive site‐directed mutagenesis and molecular modeling, reveal that, in addition to the known and previously characterized β−hairpin motif, the helix‐loop‐helix motif makes an essential contribution to the receptor/ligand binding interface. We further discuss the insight provided by the structural analyses regarding how the cysteine‐rich domains of the TNF receptor super‐family may have evolved over time.DatabaseStructural data are available in the Protein Data Bank/BioMagResBank databases under the accession codes 2KMZ, 2KN0 and 2KN1 and 17237, 17247 and 17252.Structured digital abstract

TWEAK binds to hFn14 by surface plasmon resonance (View interaction)

xeFn14 binds to TWEAK by enzyme linked immunosorbent assay (View interaction)

TWEAK binds to xeFn14 by surface plasmon resonance (View interaction)

hFn14 binds to TWEAK by enzyme linked immunosorbent assay (View interaction)
PERSPECTIVES ON DEATH, DYING AND ADVANCE CARE PLANNING FROM PATIENTS RECEIVING HAEMODIALYSIS
Authors: Collins May , Lehane Elaine 
Published: February 2013

SUMMARYBackgroundThe illness trajectory of End Stage Kidney Disease (ESKD) is not linear therefore it can be difficult for practitioners to know when end‐of‐life care begins. Advance care planning (ACP) allows patients to take part in decision making, however much of the research conducted stems from North America and Canada where individuals have experience of ACP. The aim of the study was to determine the views of Irish patients receiving haemodialysis, on death, dying and ACP.MethodsA quantitative, descriptive design was used with a convenience sample of 50 patients. Data were collected by means of a researcher administered questionnaire and analysed using descriptive statistics.FindingsThe majority of participants were comfortable talking about death, but not necessarily among family, with most desiring medical interventions to prolong life. The control of pain and other symptoms, being physically comfortable and being at peace spiritually were the most important issues at end of life.ConclusionThis study provides an insight into what is important to patients in relation to death, dying and advance care planning.
THE IMPACT OF NURSE‐LED EDUCATION ON HAEMODIALYSIS PATIENTS' PHOSPHATE BINDER MEDICATION ADHERENCE
Authors: Sandlin Kimberly , Bennett Paul N , Ockerby Cherene , Corradini Ann‐Marie 
Published: February 2013

SUMMARYBackgroundPhosphate binder medication adherence is required to maintain optimal phosphate levels and minimise bone disease in people with end stage kidney disease.ObjectivesTo examine the impact of a nurse‐led education intervention on bone disorder markers, adherence to phosphate binder medication and medication knowledge.DesignDescriptive study with a paired pre–post intervention survey.ParticipantsAdults receiving haemodialysis.MethodsTwelve‐week intervention where patients self‐administered their phosphate binder medication at each dialysis treatment. Nurses provided individualised education. Patients completed a pre‐ and post‐intervention survey designed to explore their knowledge of phosphate binders.ResultsThere were no statistically significant changes in clinical markers but a significant improvement in the proportion of patients who took their phosphate binder correctly, increasing from 44 to 72% (p = 0.016). There were moderate to large effect size changes for improved knowledge.ConclusionsA nurse‐led intervention education programme can increase patients' phosphate binder adherence. However, this does not necessarily manifest into improved serum phosphate levels.
EFFECT OF NUTRITIONAL INTERVENTION ON MALNUTRITION INDICATORS IN PATIENTS ON HAEMODIALYSIS
Authors: Roy Linda Grace , Shetty Manjunath S. , Urooj Asna 
Published: February 2013

SUMMARYObjectiveTo formulate a nutrient supplement using low cost, commonly available food ingredients and test its efficacy on various nutritional parameters in haemodialysis (HD) subjects.DesignProspective intervention study.Subjects15 subjects who did not have diabetes were recruited for the study. The subjects served as self controls.ApproachThe subjects received a multi‐nutrient formulation for a period of 3 months. Somatic status [weight, mid upper arm circumference (MUAC), mid upper arm muscle circumference (MUAMC), waist and hip measurements], biochemical parameters [blood urea nitrogen (BUN), total iron binding capacity (TIBC),serum levels of creatinine, albumin, triglycerides, sodium, potassium, calcium, phosphorus and high sensitive C‐reactive protein(HsCRP)], dietary intake and malnutrition inflammation score (MIS) were assessed.ResultsSignificant increments (P ≤ 0.01) in anthropometric measurements. Significant increases (P ≤ 0.01) in Hb, BUN, serum creatinine, albumin and total protein and a significant decrease (P ≤ 0.01) in HsCRP and MIS were observed at the end of the study. An increase in baseline food/nutrient intake was also observed.ConclusionNutritional supplementation designed for haemodialysis, improved their nutritional status in the short term study.
Combined core promoter mutations and pre‐S deletion of HBV may not increase the risk of HCC: a geographical epidemiological study in Guangxi, China
Authors: Li Guo‐Jian , Harrison Tim J. , Yang Jin‐Ye , Chen Qin‐Yan , Wang Xue‐Yan , Fang Zhong‐Liao 
Published: February 2013

AbstractBackgroundAlthough persistent hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), the mechanisms of oncogenesis remain obscure.AimsTo determine whether the findings that HBV basal core promoter (BCP) A1762T, G1764A double mutations, pre‐S deletions and a combination of both are risk factors of HCC are supported by geographical epidemiology.MethodsStudy subjects were recruited from Long An county, where the incidence of HCC is the highest, and five other counties in Guangxi, where the HCC incidence is lower and varies among them. The Pre‐S region and BCP of HBV from all study subjects were amplified and sequenced and the data were analysed using chi‐squared tests.ResultsThe prevalence of BCP and pre‐S mutations differs significantly (χ2 = 9.850, 5.135, respectively, all P < 0.01) between Long An and the other counties. However, the prevalence of combined BCP and pre‐S mutations does not differ significantly (χ2 = 1.510, P > 0.05). These mutations are less frequent in the young but the prevalence of pre‐S deletions does not increase with age. The prevalence of these mutations does not differ significantly between men and women but is significantly higher in Zhuang than the other ethnic populations. Among the other five counties, the prevalence of BCP mutations in counties where the HCC incidence is high is significantly higher than that of counties where the HCC incidence is low.ConclusionsCombined BCP double mutations and pre‐S deletion may not increase the risk of HCC, although these mutations are a risk factor of HCC when they present alone.
Educational Neuroethics: A Contribution From Empirical Research
Authors: Zocchi Meghan , Pollack Courtney 
Published: February 2013

ABSTRACTIn recent years, educational neuroscience has begun to move into the limelight, suggesting an increased importance on the ethical considerations of educational neuroscience work, or educational neuroethics. In a departure from previous work on educational neuroethics, this article focuses on the ethical considerations that are applicable to empirical educational neuroscience research. Neuroethics concepts were compiled through a thorough survey of neuroethics articles. Then, 28 empirical educational neuroscience articles were analyzed through the lens of five categories of neuroethics concepts collected through the literature survey: the scientific enterprise, prediction, neuro‐manipulation, social considerations, and philosophical considerations. Three of the five categories (i.e., the nature of scientific investigation, prediction, and social considerations) applied to a subset of the articles. In addition, a fourth ethical issue not stemming from the neuroethics literature, referred to here as brain‐based justifications, emerged from the nature of educational neuroscience work. Limitations of this study and future directions for educational neuroethics research are discussed.
Impact of Using a Telescoping‐Support Catheter System for Left Ventricular Lead Placement on Implant Success and Procedure Time of Cardiac Resynchronization Therapy
Authors: JACKSON KEVIN P. , HEGLAND DONALD D. , FRAZIER‐MILLS CAMILLE , PICCINI JONATHAN P. , KOONTZ JASON I. , ATWATER BRETT D. , DAUBERT JAMES P. , WORLEY SETH J. 
Published: February 2013

BackgroundProper positioning of the left ventricular (LV) lead improves clinical outcomes and survival in patients receiving cardiac resynchronization therapy (CRT). Techniques of LV lead insertion using contrast injection and a telescoping system of delivery catheters to support advancement of the lead into the target branch may allow more efficient, targeted lead placement. We sought to evaluate the impact of an LV lead implant approach using telescoping‐support catheters (group TS) on success rate, lead location, and procedural time compared to standard over‐the‐wire implant techniques (group OTW).MethodsFour hundred thirty‐seven consecutive patients undergoing CRT implantation were divided into group TS (n = 105) or group OTW (n = 332) based upon a review of the operative technique used for LV lead implantation. The primary outcome was success of LV lead implantation at the index procedure. Secondary endpoints included optimal positioning of the LV lead and reduction in procedural fluoroscopy time.ResultsFailed LV lead placement was lower (1.9% vs 8.1%, P = 0.02) and optimal lead positioning was achieved more often for group TS than group OTW (87% vs 75%, P = 0.01). In addition, there were significantly shorter fluoroscopy times for group TS versus group OTW (29.6 minutes vs 41.9 minutes, P < 0.01).ConclusionA CRT‐implant approach using contrast injection and a telescoping‐support catheter system results in fewer failed LV lead implants, improved LV lead location, and shorter procedure times.
Wenxin Keli Suppresses Ventricular Triggered Arrhythmias via Selective Inhibition of Late Sodium Current
Authors: XUE XIAOLIN , GUO DONGLIN , SUN HONGMEI , WANG DAN , LI JIANA , LIU TENGXIAN , YANG LIN , SHU JUAN , YAN GAN‐XIN 
Published: February 2013

BackgroundWenxin Keli is a popular Chinese herb extract that approximately five million Asians are currently taking for the treatment of a variety of ventricular arrhythmias. However, its electrophysiological mechanisms remain poorly understood.Methods and resultsThe concentration‐dependent electrophysiological effects of Wenxin Keli were evaluated in the isolated rabbit left ventricular myocytes and wedge preparation. Wenxin Keli selectively inhibited late sodium current (INa) with an IC50 of 3.8 ± 0.4 mg/mL, which was significantly lower than the IC50 of 10.6 ± 0.9 mg/mL (n = 6, P < 0.05) for the fast INa. Wenxin Keli produced a small but statistically significant QT prolongation at 0.3 mg/mL, but shortened the QT and Tp–e interval at concentrations ≥1 mg/mL. Wenxin Keli increased QRS duration by 10.1% from 34.8 ± 1.0 ms to 38.3 ± 1.1 ms (n = 6, P < 0.01) at 3 mg/mL at a basic cycle length of 2,000 ms. However, its effect on the QRS duration exhibited weak use‐dependency, that is, QRS remained less changed at increased pacing rates than other classic sodium channel blockers, such as flecainide, quinidine, and lidocaine. On the other hand, Wenxin Keli at 1–3 mg/mL markedly reduced dofetilide‐induced QT and Tp–e prolongation by attenuation of its reverse use‐dependence and abolished dofetilide‐induced early afterdepolarization (EAD) in four of four left ventricular wedge preparations. It also suppressed digoxin‐induced delayed afterdepolarization (DAD) and ventricular tachycardias without changing the positive staircase pattern in contractility at 1–3 mg/mL in a separate experimental series (four of four).ConclusionsWenxin Keli suppressed EADs, DADs, and triggered ventricular arrhythmias via selective inhibition of late INa.
The Ties that Bind: An Analysis of the Concept of Obligation
Authors: Himma Kenneth Einar 
Published: February 2013

AbstractLegal positivism lacks a comprehensive theory of legal obligation. Hart's account of legal obligation, if successful, would explain only how the rule of recognition obligates officials. There is nothing in Hart's account of social obligation and social norms that would explain how the legal norms that govern citizen behavior give rise to legal obligations. However, we cannot give a theoretical explanation of the concept of legal obligation without a theoretical explanation of the concept of obligation. If legal, social and moral obligations are three instances of the kind defined by “obligation,” then we cannot successfully explicate the nature of legal, social or moral obligations without a successful general conceptual theory of obligation. In what follows, I attempt to develop what I take to be the central elements of the general concept of obligation. I argue that obligations are (1) associated with mandatory prescriptions; (2) reasons for action; (3) exclusionary in the sense that certain reasons are excluded as an excuse of justification for non‐performance; and (4) “binding” in the sense that they have a special normative force. At the end of the paper, I briefly argue that our shared concept of obligation is indeterminate with respect to one theoretically important case, the issue of whether the rules of a crime gang that includes some sort of rule‐defining procedures for making rules governing members obligate gang members if accepted as legitimate by the members.
How Rights Became “Subjective”
Authors: Mautner Thomas 
Published: February 2013

AbstractWhat is commonly called a right has since about 1980 increasingly come to be called a subjective right. In this paper the origin and rise of this solecism is investigated. Its use can result in a lack of clarity and even confusion. Some aspects of rights‐concepts and their history are also discussed. A brief postscript introduces Leibniz's Razor.
The alarmin HMGB‐1 influences healing outcomes in fetal skin wounds
Authors: Dardenne Adrienne D. , Wulff Brian C. , Wilgus Traci A. 
Published: February 2013

AbstractIn mice, cutaneous wounds generated early in development (embryonic day 15, E15) heal scarlessly, while wounds generated late in gestation (embryonic day 18, E18) heal with scar formation. Even though both types of wounds are generated in the same sterile uterine environment, scarless fetal wounds heal without inflammation, but a strong inflammatory response is observed in scar‐forming fetal wounds. We hypothesized that altered release of alarmins, endogenous molecules that trigger inflammation in response to damage, may be responsible for the age‐related changes in inflammation and healing outcomes in fetal skin. The purpose of this study was to determine whether the alarmin high‐mobility group box‐1 (HMGB‐1) is involved in fetal wound repair. Immunohistochemical analysis showed that in unwounded skin, E18 keratinocytes expressed higher levels of HMGB‐1 compared with E15 keratinocytes. After injury, HMGB‐1 was released to a greater extent from keratinocytes at the margin of scar‐forming E18 wounds, compared with scarless E15 wounds. Furthermore, instead of healing scarlessly, E15 wounds healed with scars when treated with HMGB‐1. HMGB‐1‐injected wounds also had more fibroblasts, blood vessels, and macrophages compared with control wounds. Together, these data suggest that extracellular HMGB‐1 levels influence the quality of healing in cutaneous wounds.
Estimating the 4D respiratory lung motion by spatiotemporal registration and super‐resolution image reconstruction
Authors: Wu Guorong , Wang Qian , Lian Jun , Shen Dinggang 
Published: February 2013

Purpose:One of the main challenges in lung cancer radiation therapy is how to reduce the treatment margin but accommodate the geometric uncertainty of moving tumor. 4D‐CT is able to provide the full range of motion information for the lung and tumor. However, accurate estimation of lung motion with respect to the respiratory phase is difficult due to various challenges in image registration, e.g., motion artifacts and large interslice thickness in 4D‐CT. Meanwhile, the temporal coherence across respiration phases is usually not guaranteed in the conventional registration methods which consider each phase image in 4D‐CT independently. To address these challenges, the authors present a unified approach to estimate the respiratory lung motion with two iterative steps.Methods:First, the authors propose a novel spatiotemporal registration algorithm to align all phase images of 4D‐CT (in low‐resolution) to a high‐resolution group‐mean image in the common space. The temporal coherence of registration is maintained by a set of temporal fibers that delineate temporal correspondences across different respiratory phases. Second, a super‐resolution technique is utilized to build the high‐resolution group‐mean image with more anatomical details than any individual phase image, thus largely alleviating the registration uncertainty especially in correspondence detection. In particular, the authors use the concept of sparse representation to keep the group‐mean image as sharp as possible.Results:The performance of our 4D motion estimation method has been extensively evaluated on both the simulated datasets and real lung 4D‐CT datasets. In all experiments, our method achieves more accurate and consistent results in lung motion estimation than all other state‐of‐the‐art approaches under comparison.Conclusions:The authors have proposed a novel spatiotemporal registration method to estimate the lung motion in 4D‐CT. Promising results have been obtained, which indicates the high applicability of our method in clinical lung cancer radiation therapy.
Design and baseline characteristics of the PODOSA (Prevention of Diabetes & Obesity in South Asians) trial: a cluster, randomised lifestyle intervention in Indian and Pakistani adults with impaired glycaemia at high risk of developing type 2 diabetes
Authors: Douglas Anne , Bhopal Raj S , Bhopal Ruby , Forbes John F , Gill Jason M R , McKnight John , Murray Gordon , Sattar Naveed , Sharma Anu , Wallia Sunita , Wild Sarah , Sheikh Aziz 
Published: February 2013

ObjectivesTo describe the design and baseline population characteristics of an adapted lifestyle intervention trial aimed at reducing weight and increasing physical activity in people of Indian and Pakistani origin at high risk of developing type 2 diabetes.DesignCluster, randomised controlled trial.SettingCommunity-based in Edinburgh and Glasgow, Scotland, UK.Participants156 families, comprising 171 people with impaired glycaemia, and waist sizes ≥90 cm (men) and ≥80 cm (women), plus 124 family volunteers.InterventionsFamilies were randomised into either an intensive intervention of 15 dietitian visits providing lifestyle advice, or a light (control) intervention of four visits, over a period of 3 years.Outcome measuresThe primary outcome is a change in mean weight between baseline and 3 years. Secondary outcomes are changes in waist, hip, body mass index, plasma blood glucose and physical activity. The cost of the intervention will be measured. Qualitative work will seek to understand factors that motivated participation and retention in the trial and families’ experience of adhering to the interventions.ResultsBetween July 2007 and October 2009, 171 people with impaired glycaemia, along with 124 family volunteers, were randomised. In total, 95% (171/196) of eligible participants agreed to proceed to the 3-year trial. Only 13 of the 156 families contained more than one recruit with impaired glycaemia. We have recruited sufficient participants to undertake an adequately powered trial to detect a mean difference in weight of 2.5 kg between the intensive and light intervention groups at the 5% significance level. Over half the families include family volunteers. The main participants have a mean age of 52 years and 64% are women.ConclusionsPrevention of Diabetes & Obesity in South Asians (PODOSA) is one of the first community-based, randomised lifestyle intervention trials in a UK South Asian population. The main trial results will be submitted for publication during 2013.Trial registrationCurrent controlled trialsISRCTN25729565(http://www.controlled-trials.com/isrctn/).