bluuebunny/crossref_metadata_2025_split huggingface dataset:
The networks of care surrounding cancer palliative care patients
Authors: Jarrett N , Porter K , Davis C , Addington-Hall J , Duke S , Corner J , Lathlean J 
Published: March 2015

ObjectivesThis paper explicates the nature and extent of the networks of care surrounding patients with cancer palliative care needs.MethodTwenty-four patients with 15 different types/sites of cancer were recruited in one city in England, UK. During one in-depth interview patients identified who was ‘involved in their care’ and any known pathways of communication between them. One hundred of these people (35 doctors, 32 nurses, 17 professions allied to medicine, 8 family members and 8 others) were also interviewed. Maps of people/teams and the connections between them for each patient were then reconstructed using social networking software (PAJEK).ResultsThe 24 patients identified a total of 619 people or teams (mean 26, median 22, range 9–45 per patient) contributing to their care. Selected care network maps are displayed, illustrating the extent and nature of the care networks supporting palliative care patients. Common members of care networks for patients with palliative care needs are revealed, but their individual and unique nature is also apparent.ConclusionsThe possible clinical utility and challenges of mapping care networks are discussed. Exploring the care networks surrounding individual patients can be useful for illuminating the extent and complexity of individual patient's care networks; clarifying who is involved and who they communicate with; providing opportunities to see interaction routes that may otherwise be hidden, revealing potentially missing or weak connections; and highlighting overlaps or gaps in provision.
‘Quality End of Life Care for All’ (QELCA): the national rollout of an end-of-life workforce development initiative
Authors: Gillett Karen , Bryan Liz 
Published: March 2015

BackgroundMost people in the UK die in National Health Service (NHS) hospitals and it is essential that NHS employees are equipped to provide high-quality end-of-life care. Government policy encourages charities to work in partnership with the NHS and hospices have the necessary expertise to deliver education in end-of-life care.InterventionThis article describes the national rollout and evaluation of the ‘Quality End of Life Care for All’ (QELCA) programme funded by the NHS National End of Life Care Programme. QELCA enables health professionals from acute NHS trusts to experience hospice care and empowers them to improve end-of-life care in their own practice settings. Seventeen acute NHS trusts took part with 21 hospices local to the trusts delivering the programme. Overall, 137 acute nurses participated in the programme, which involved 5 days at the hospice followed by 6 months of action-learning sets.OutcomeParticipants gave concrete examples of improvements they made to end-of-life care and the majority of those who returned postcourse questionnaires believed that QELCA had changed their practice. Additional positive outcomes included better working relationships between acute trusts and hospices, and more appropriate referrals.DiscussionParticipants in QELCA progressed from passively identifying problems to actively problem solving and facilitating changes in practice. This attitudinal change has the potential to stimulate and sustain real change in end-of-life care in acute hospitals. QELCA is now being delivered to other members of the multidisciplinary team, including general practitioners.
Hic-5 Mediates TGFβ–Induced Adhesion in Vascular Smooth Muscle Cells by a Nox4-Dependent Mechanism
Authors: Fernandez Isabel , Martin-Garrido Abel , Zhou Dennis W. , Clempus Roza E. , Seidel-Rogol Bonnie , Valdivia Alejandra , Lassègue Bernard , García Andrés J. , Griendling Kathy K. , San Martin Alejandra 
Published: March 2015

Objective—

Focal adhesions (FAs) link the cytoskeleton to the extracellular matrix and as such play important roles in growth, migration, and contractile properties of vascular smooth muscle cells. Recently, it has been shown that downregulation of Nox4, a transforming growth factor (TGF) β-inducible, hydrogen peroxide (H
2
O
2
)–producing enzyme, affects the number of FAs. However, the effectors downstream of Nox4 that mediate FA regulation are unknown. The FA resident protein H
2
O
2
-inducible clone (Hic)-5 is H
2
O
2
and TGFβ inducible, and a binding partner of the heat shock protein (Hsp) 27. The objective of this study was to elucidate the mechanism, by which Hic-5 and Hsp27 participate in TGFβ-induced, Nox4-mediated vascular smooth muscle cell adhesion and migration.

Approach and Results—
Through a combination of molecular biology and biochemistry techniques, we found that TGFβ, by a Nox4-dependent mechanism, induces the expression and interaction of Hic-5 and Hsp27, which is essential for Hic-5 localization to FAs. Importantly, we found that Hic-5 expression is required for the TGFβ-mediated increase in FA number, adhesive forces and migration. Mechanistically, Nox4 downregulation impedes Smad (small body size and mothers against decapentaplegic) signaling by TGFβ, and Hsp27 and Hic-5 upregulation by TGFβ is blocked in small body size and mothers against decapentaplegic 4–deficient cells.

Conclusions—
Hic-5 and Hsp27 are effectors of Nox4 required for TGFβ-stimulated FA formation, adhesion strength and migration in vascular smooth muscle cell.
Nonbiased Molecular Screening Identifies Novel Molecular Regulators of Fibrogenic and Proliferative Signaling in Myxomatous Mitral Valve Disease
Authors: Thalji Nassir M. , Hagler Michael A. , Zhang Heyu , Casaclang-Verzosa Grace , Nair Asha A. , Suri Rakesh M. , Miller Jordan D. 
Published: March 2015

Background—
Pathological processes underlying myxomatous mitral valve degeneration (MMVD) remain poorly understood. We sought to identify novel mechanisms contributing to the development of this condition.

Methods and Results—

Microarrays were used to measure gene expression in 11 myxomatous and 11 nonmyxomatous human mitral valves. Differential gene expression (thresholds
P
<0.05; fold-change >1.5) and pathway activation (Ingenuity) were confirmed using quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Contributions of bone morphogenetic protein 4 and transforming growth factor (TGF)-β2 to differential gene expression were evaluated in vitro. Contributions of angiotensin II to differential pathway activation were examined in mice in vivo. A total of 2602 genes were differentially expressed between myxomatous and nonmyxomatous valves. Canonical TGF-β signaling was increased in MMVD because of increased ligand expression and derepression of SMA mothers against decapentaplegic 2/3 signaling and was confirmed with quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Myxomatous valves demonstrated activation of canonical bone morphogenetic protein and Wnt/β-catenin signaling and upregulation of their common target runt-related transcription factor 2. Our data set provided transcriptional and immunohistochemical evidence for activated immune cell infiltration. In vitro treatment of mitral valve interstitial cells with TGF-β2 increased β-catenin signaling at mRNA and protein levels, suggesting interactions between TGF-β2 and Wnt signaling. In vivo infusion of mice with angiotensin II recaptured several changes in signaling pathways characteristic of human MMVD.

Conclusions—
These data support a new disease framework whereby activation of TGF-β2, bone morphogenetic protein 4, Wnt/β-catenin, or immune signaling plays major roles in the pathogenesis of MMVD. We propose these pathways act in a context-dependent manner to drive phenotypic changes that fundamentally differ from those observed in aortic valve disease and open novel avenues guiding future research into the pathogenesis of MMVD.
Genetic Variations in MicroRNA-Binding Sites Affect MicroRNA-Mediated Regulation of Several Genes Associated With Cardio-metabolic Phenotypes
Authors: Ghanbari Mohsen , Franco Oscar H. , de Looper Hans W.J. , Hofman Albert , Erkeland Stefan J. , Dehghan Abbas 
Published: March 2015

Background—
Genome-wide association studies enabled us to discover a large number of variants and genomic loci contributing to cardiovascular and metabolic disorders. However, because the vast majority of the identified variants are thought to merely be proxies for other functional variants, the causal mechanisms remain to be elucidated. We hypothesized that the part of the functional variants involved in deregulating cardiometabolic genes is located in microRNA (miRNA)-binding sites.

Methods and Results—

Using the largest genome-wide association studies available on glycemic indices, lipid traits, anthropometric measures, blood pressure, coronary artery diseases, and type 2 diabetes mellitus, we identified 11 067 variants that are associated with cardiometabolic phenotypes. Of these, 230 variants are located within miRNA-binding sites in the 3′-untranslated region of 155 cardiometabolic genes. Thirty-seven of 230 variants were found to fulfill our predefined criteria for being functional in their genomic loci. Ten variants were subsequently selected for experimental validation based on genome-wide association studies results, expression quantitative trait loci (eQTL) analyses, and coexpression of their host genes and regulatory miRNAs in relevant tissues. Luciferase reporter assays revealed an allele-specific regulation of genes hosting the variants by miRNAs. These cotransfection experiments showed that rs174545 (
FADS1
:miR-181a-2), rs1059611 (
LPL
:miR-136), rs13702 (
LPL
:miR-410), rs1046875 (
FN3KRP
:miR-34a), rs7956 (
MKRN2
:miR-154), rs3217992 (
CDKN2B
:miR-138-2-3p), and rs11735092 (
HSD17B13
:miR-375) decrease or abrogate miRNA-dependent regulation of the genes. Conversely, 2 variants, rs6857 (
PVRL2
:miR-320e) and rs907091 (
IKZF3
:miR-326), were shown to enhance the activity of miRNAs on their host genes.

Conclusions—
We provide evidence for a model in which polymorphisms in miRNA-binding sites can both positively and negatively affect miRNA-mediated regulation of cardiometabolic genes.
Four-Year Follow-Up of Transient Ischemic Attacks, Strokes, and Mimics
Authors: Dutta Dipankar , Bowen Emily , Foy Chris 
Published: March 2015

Background and Purpose—
There is limited information on outcomes from rapid access transient ischemic attack (TIA) clinics. We present 4-year outcomes of TIAs, strokes, and mimics from a UK TIA clinic database.

Methods—
All patients referred between April 2010 and May 2012 were retrospectively identified and outcomes determined. End points were stroke, myocardial infarction, any vascular event (TIA, stroke, or myocardial infarction), and all-cause death. Data were analyzed by survival analysis.

Results—
Of 1067 patients, 31.6% were TIAs, 18% strokes, and 50.4% mimics. Median assessment time was 4.5 days from onset and follow-up was for 34.9 months. Subsequent strokes occurred in 7.1% of patients with TIA, 10.9% of patients with stroke, and 2.0% of mimics at the end of follow-up. Stroke risk at 90 days was 1.3% for patients diagnosed as TIA or stroke. Compared with mimics, hazard ratios for subsequent stroke were 3.88 (1.90–7.91) for TIA and 5.84 (2.81–12.11) for stroke. Hazard ratio for any subsequent vascular event was 2.91 (1.97–4.30) for TIA and 2.83 (1.81–4.41) for stroke. Hazard ratio for death was 1.68 (1.10–2.56) for TIA and 2.19 (1.38–3.46) for stroke.

Conclusions—
Our results show a lower 90-day stroke incidence after TIA or minor stroke than in earlier studies, suggesting that rapid access daily TIA clinics may be having a significant effect on reducing strokes.
Impact of Initial Conditions versus External Forcing in Decadal Climate Predictions: A Sensitivity Experiment*
Authors: Corti Susanna , Palmer Tim , Balmaseda Magdalena , Weisheimer Antje , Drijfhout Sybren , Dunstone Nick , Hazeleger Wilco , Kröger Jürgen , Pohlmann Holger , Smith Doug , Storch Jin-Song von , Wouters Bert 
Published: March 2015

Abstract
The impact of initial conditions relative to external forcings in decadal integrations from an ensemble of state-of-the-art prediction models has been assessed using specifically designed sensitivity experiments (SWAP experiments). They consist of two sets of 10-yr-long ensemble hindcasts for two initial dates in 1965 and 1995 using either the external forcings from the “correct” decades or swapping the forcings between the two decades. By comparing the two sets of integrations, the impact of external forcing versus initial conditions on the predictability over multiannual time scales was estimated as the function of lead time of the hindcast. It was found that over time scales longer than about 1 yr, the predictability of sea surface temperatures (SSTs) on a global scale arises mainly from the external forcing. However, the correct initialization has a longer impact on SST predictability over specific regions such as the North Atlantic, the northwestern Pacific, and the Southern Ocean. The impact of initialization is even longer and extends to wider regions when below-surface ocean variables are considered. For the western and eastern tropical Atlantic, the impact of initialization for the 700-m heat content (HTC700) extends to as much as 9 years for some of the models considered. In all models the impact of initial conditions on the predictability of the Atlantic meridional overturning circulation (AMOC) is dominant for the first 5 years.
Pulmonary Rehabilitation After Total Laryngectomy
Authors: Parrilla Claudio , Minni Antonio , Bogaardt Hans , Macri Gian Franco , Battista Mariapina , Roukos Raymond , Pandolfini Manlio , Ruoppolo Giovanni , Paludetti Gaetano , D’Alatri Lucia , de Vincentiis Marco 
Published: March 2015

Background: Both the immediate beneficial physiological changes in a laboratory setting and the long-term clinical outcomes of heat and moisture exchanger (HME) use are well described. So far, there has not been any research published that provides detailed insight in the pattern of changes in both respiratory function and patients’ experiences with HMEs in the first weeks of use. Methods: A multicenter time-series study design with a 2-week double baseline period. All patients used the XtraHME for 12 weeks afterward. Data were collected 2 weeks, 6 weeks, and 12 weeks after the start of HME use. Results: Data of 30 patients were analyzed. Pulmonary symptoms decreased significantly during the 12 weeks of HME use. After 2 weeks, a significant decrease in daily coughs and daily forced expectorations was seen. The general quality of life showed a significant increase throughout the study. More general physical complaints also significantly decreased with HME use. Patient satisfaction with the HME was high. Conclusions: This study shows that there is a significant influence of the XtraHME on pulmonary status that can already be observed after 2 weeks of using the XtraHME and continues to improve further after 6 weeks of XtraHME use.
Pushing the limits of chemistry point-of-care testing for the management of patients under investigation for Ebola virus disease
Authors: LeBlanc Jason J , Heinstein Charles , MacDonald James , Gallant Roy , Roberts Catherine , Jackson Colleen , Lou Amy , Nassar Bassam A , Hatchette Todd F 
Published: March 2015

Background With the recent outbreak in West Africa, hospitals worldwide have been developing protocols for suspect of cases of Ebola virus disease. Patients with Ebola virus disease present with a severe gastroenteritis leading to dehydration and electrolyte abnormalities and as such, routine chemistry analysis is essential for patient management. While point-of-care testing can be used with additional precautions for rapid chemistry analyses in a laboratory setting, significant delays could ensue before specimens arrive to the laboratory. This study evaluated the stability of eight chemistry analytes up to 4 h post-collection. Methods Blood was collected by venipuncture from 20 healthy volunteers and tested at times 0, 30, 60, 90, 120 and 240 h. Approximately 100 µl of blood was dispensed into a CHEM 8+Cartridge and processed on a model 300 i-STAT 1 Analyzer (Abbott Point of Care Inc.) and ANOVA was used to assess statistical significant difference from the initial time point. Results While the manufacturer recommends testing within 30 min of collection, no significant variation was observed for most analytes with time points extending up to 4 h. In contrast, glucose concentrations decreased significantly ( P < 0.0001) over time at an average rate of 0.0032 mmol/L per min. Conclusions This study provides supporting data suggesting that delays up to 4 h can be tolerated, giving ample time for collection and transport of specimens to the clinical laboratory. For glucose, POC testing could still be used, taking into account the collection time and the average rate of decrease.
Should an increase in cerebral neurochemicals following head kicks in full contact karate influence return to play?
Authors: Graham MR , Pates J , Davies B , Cooper SM , Bhattacharya K , Evans PJ , Baker JS 
Published: March 2015

Background: Cerebral neurochemicals are markers of traumatic brain injury (TBI). Objectives: The aim of the study was to determine whether kicks to the head (KTH) in full contact karate significantly increased serum concentrations of protein S-100B, and neurone specific enolase (NSE). Kicks to the body (KTB) were also quantified to asses muscle tissue injury. Muscle damage was assessed by analysis of serum total creatine kinase (CK). Methods: Twenty-four full contact karate practitioners were observed and filmed during actual competition and divided into two main groups post event: (1) Kicks to the head and body group (KTH): n = 12; mean ± SD; age, 30.4 ± 6.7 years; height, 1.74 ± 0.1 m; weight, 79.1 ± 2.1 kg; and (2): Kicks to the body group (KTB): n = 12; mean ± SD; age, 28.2 ± 6.5 years; height, 1.75 ± 0.1 m; weight, 79.2 ± 1.7 kg. The KTH group received direct kicks to the head, while group KTB received kicks and punches to the body. Blood samples were taken before and immediately post-combat for analysis of serum S-100B, NSE, CK and cardiac troponin. Results: Significant increases in serum concentrations of S-100B (0.12 ± 0.17 vs. 0.37 ± 0.26, µg.L−1) and NSE (11.8 ± 4.1 vs. 20.2 ± 9.1 ng.mL−1) were encountered after combat in the KTH group and CK (123 ± 53 vs. 184 ± 103 U.L−1) in the KTB group (all P <0.05). Conclusions: Head kicks in full contact karate cause elevation of neurochemical markers associated with damaged brain tissue. The severity of injury is related to the early post-traumatic release of protein S-100B and NSE. The early kinetics and appearance post injury can reflect intracranial pathology, and suggest S-100B and NSE are extremely sensitive prognostic markers of TBI.
Can argyrophilic nucleolar organizing region-associated protein amount be used for the detection of cardiac damage?
Authors: Kandiş H , Afacan MA , Eröz R , Colakoglu S , Bayramoglu A , Oktay M , Saritas A , Colak S , Kaya M , Kara İH 
Published: March 2015

Introduction: Carbon monoxide (CO) is a colorless, tasteless, odorless, nonirritant gas and CO poisoning affects all organ systems. Aim: We aimed to detect any possible effects of CO exposure on the argyrophilic nucleolar organizing region (AgNOR)-associated protein synthesis of heart cells and whether there is any relationship between AgNOR protein amount and both carboxyhemoglobin (COHb) level and histopathological evaluation methods used for the detection of damage in heart tissue after CO exposure. Materials and Methods: The rats were divided into four groups (control, 1000, 3000, and 5000 ppm), each containing six rats. After CO intoxication, COHb levels were measured and the animals were killed on the 7th day. AgNOR staining was performed in the heart tissue. One hundred nuclei per rat were evaluated, and total AgNOR area/nuclear area and mean AgNOR number were analyzed for each nucleus. The CO exposure groups had significantly higher AgNOR values than the control group ( p < 0.0001). According to cardiomyopathy (CMY) scoring methods, the differences between groups 3 and 4 and groups 1 and 2 were significant ( p < 0.05). A significant positive correlation between AgNOR values and both CMY and COHb levels were detected. Conclusion: The detection of AgNOR protein amount may give information about the CMY levels and be used to detect the CO intoxication levels instead of COHb in later periods.
Value of pentraxin-3 and galectin-3 in acute coronary syndrome: a short-term prospective cohort study
Authors: George Melvin , Shanmugam Elangovan , Srivatsan Varsha , Vasanth Karunamoorthy , Ramraj Balaji , Rajaram Muthukumar , Jena Amrita , Sridhar Aruna , Chaudhury Minakshi , Kaliappan Ilango 
Published: March 2015

Background: Acute coronary syndrome (ACS) continues to be a leading cause of morbidity and mortality worldwide. Galectin-3 and pentraxin-3 are two prognostic biomarkers that have been studied in heart failure (HF). However, there are limited data on these biomarkers in the ACS population. The objective of the study was to determine the variables that are most affected by high concentrations of pentraxin-3 and galectin-3, and the influence they have on outcomes of all-cause mortality in patients with ACS. Methods: We included a total of 160 patients [ST elevation myocardial infarction (STEMI), n = 64; non STEMI/unstable angina (NSTEMI/UA), n = 38; and control subjects with chronic stable angina (CSA)/microvascular angina (MVA) n = 58]. Plasma pentraxin-3 and galectin-3 levels were assessed from these patients at the time of hospital admission. Major adverse cardiovascular events including all-cause mortality, rehospitalizations and coronary artery bypass graft surgery (CABG) were assessed at 6 months. Results: The median concentration of pentraxin-3 and galectin-3 were significantly higher in STEMI than in NSTEMI patients ( p < 0.005) or controls ( p < 0.005). Greater numbers of deaths (4 versus 0) were observed in STEMI patients with higher levels of these biomarkers. In addition, ACS patients with high levels of pentraxin-3 and galectin-3 had lower left ventricular ejection fraction (LVEF) ( p < 0.005), and a moderate correlation was observed between LVEF and pentraxin-3 levels ( r = -0.45, p < 0.005). Patients with higher galectin-3 levels were also observed to have a lower estimated glomerular fraction rate (eGFR), and a moderate correlation was observed between them ( r = -0.34, p < 0.005). Conclusion: Pentraxin-3 and galectin-3 hold much promise in the ACS population as prognostic biomarkers.