bluuebunny/crossref_metadata_2025_split huggingface dataset:
ERK-Dependent Downregulation of the Atypical Chemokine Receptor D6 Drives Tumor Aggressiveness in Kaposi Sarcoma
Authors: Savino Benedetta , Caronni Nicoletta , Anselmo Achille , Pasqualini Fabio , Borroni Elena Monica , Basso Gianluca , Celesti Giuseppe , Laghi Luigi , Tourlaki Athanasia , Boneschi Vinicio , Brambilla Lucia , Nebuloni Manuela , Vago Gianluca , Mantovani Alberto , Locati Massimo , Bonecchi Raffaella 
Published: April 2014

AbstractD6 is an atypical chemokine receptor acting as a decoy and scavenger for inflammatory CC chemokines expressed in lymphatic endothelial cells. Here, we report that D6 is expressed in Kaposi sarcoma (KS), a tumor ontogenetically related to the lymphatic endothelium. Both in human tumors and in an experimental model, D6 expression levels were inversely correlated with tumor aggressiveness and increased infiltration of proangiogenic macrophages. Inhibition of monocyte recruitment reduced the growth of tumors, while adoptive transfer of wild-type, but not CCR2−/− macrophages, increased the growth rate of D6-competent neoplasms. In the KS model with the B-Raf V600E–activating mutation, inhibition of B-Raf or the downstream ERK pathway induced D6 expression; in progressing human KS tumors, the activation of ERK correlates with reduced levels of D6 expression. These results indicate that activation of the K-Ras–B-Raf–ERK pathway during KS progression downregulates D6 expression, which unleashes chemokine-mediated macrophage recruitment and their acquisition of an M2-like phenotype supporting angiogenesis and tumor growth. Combined targeting of CCR2 and the ERK pathway should be considered as a therapeutic option for patients with KS. Cancer Immunol Res; 2(7); 679–89. ©2014 AACR.
Epidemiology of first and recurrent venous thromboembolism: A population-based cohort study in patients without active cancer
Authors: Cohen Alexander T. , Bamber Luke , Rietbrock Stephan , Martinez Carlos 
Published: April 2014

SummaryContemporary data from population studies on the incidence and complications of venous thromboembolism (VTE) are limited. An observational cohort study was undertaken to estimate the incidence of first and recurrent VTE. The cohort was identified from all patients in the UK Clinical Practice Research Datalink (CPRD) with additional linked information on hospitalisation and cause of death. Between 2001 and 2011, patients with first VTE were identified and the subset without active cancer-related VTE observed for up to 10 years for recurrent VTE. The 10-year cumulative incidence rates (CIR) were derived with adjustment for mortality as a competing risk event. A total of 35,373 first VTE events (12,073 provoked, 16,708 unprovoked and 6592 active cancer-associated VTE) among 26.9 million person-years of observation were identified. The overall incidence rate (IR) of VTE was 131.5 (95% CI, 130.2–132.9) per 100,000 person-years and 107.0 (95% CI, 105.8–108.2) after excluding cancer-associated VTE. DVT was more common in the young and PE was more common in the elderly. VTE recurrence occurred in 3671 (CIR 25.2%). The IR for recurrence peaked in the first six months at around 11 per 100 person years. It levelled out after three years and then remained at around 2 per 100 person years from year 4–10 of follow-up. The IRs for recurrences were particularly high in young men. In conclusion, VTE is common and associated with high recurrence rates. Effort is required to prevent VTE and to reduce recurrences.
Peri-interventional endothelin-A receptor blockade improves long-term outcome in patients with ST-elevation acute myocardial infarction
Authors: Adlbrecht Christopher , Wurm Raphael , Humenberger Michael , Andreas Martin , Redwan Bassam , Distelmaier Klaus , Klappacher Günter , Lang Irene M. 
Published: April 2014

SummaryEndothelin (ET)-1 is a pro-fibrotic vasoconstrictive peptide causing microvascular dysfunction and cardiac remodelling after acute ST-elevation myocardial infarction (STEMI). It acts via two distinct receptors, ET-A and ET-B, and is involved in inflammation and atherogenesis. Patients with posterior-wall STEMI were randomly assigned to intravenous BQ-123 at 400 nmol/minute (min) or placebo over 60 min, starting immediately prior to primary percutaneous coronary intervention (n=54). Peripheral blood samples were drawn at baseline as well as after 24 hours and 30 days. Myeloperoxidase (MPO), as a marker of neutrophil activation and matrix metalloproteinase 9 (MMP-9), a marker of extracellular matrix degradation were measured in plasma. Clinical follow-up was conducted by an investigator blinded to treatment allocation over three years. During the median follow-up period of 3.6 years (interquartile range [IQR] 3.3–4.1) we observed a longer event-free survival in patients randomised to receive BQ-123 compared with patients randomised to placebo (mean 4.5 years (95% confidence interval: 3.9–5) versus mean 3 years (2.2–3.7), p=0.031). Patients randomised to ET-A receptor blockade demonstrated a greater reduction of MPO levels from baseline to 24 hours compared to placebo-treated patients (-177 ng/ml (IQR 103–274) vs –108 ng/ml (74–147), p=0.006). In addition, a pronounced drop in MMP-9 levels (-568 ng/ml (44–1157) vs –117 ng/ml (57–561), p=0.018) was observed. There was no significant difference in amino-terminal propetide of pro-collagen type III levels. In conclusion, short-term administration of BQ-123 leads to a reduction in MPO, as well as MMP-9 plasma levels and to a longer event-free survival in patients with STEMI.ClinicalTrials.gov Identifier: NCT00502528
Potent and specific inhibition of the biological activity of the type-II transmembrane serine protease matriptase by the cyclic microprotein MCoTI-II
Authors: Gray Kelly , Elghadban Salma , Thongyoo Panumart , Owen Kate A. , Szabo Roman , Bugge Thomas H. , Tate Edward W. , Leatherbarrow Robin J. , Ellis Vincent 
Published: April 2014

SummaryMatriptase is a type-II transmembrane serine protease involved in epithelial homeostasis in both health and disease, and is implicated in the development and progression of a variety of cancers. Matriptase mediates its biological effects both via as yet undefined substrates and pathways, and also by proteolytic cleavage of a variety of well-defined protein substrates, several of which it shares with the closely-related protease hepsin. Development of targeted therapeutic strategies will require discrimination between these proteases. Here we have investigated cyclic microproteins of the squash Momordica cochinchinensis trypsin-inhibitor family (generated by total chemical synthesis) and found MCoTI-II to be a high-affinity (Ki 9 nM) and highly selective (> 1,000-fold) inhibitor of matriptase. MCoTI-II efficiently inhibited the proteolytic activation of pro-hepatocyte growth factor (HGF) by matriptase but not by hepsin, in both purified and cell-based systems, and inhibited HGF-dependent cell scattering. MCoTI-II also selectively inhibited the invasion of matriptase-expressing prostate cancer cells. Using a model of epithelial cell tight junction assembly, we also found that MCoTI-II could effectively inhibit the re-establishment of tight junctions and epithelial barrier function in MDCK-I cells after disruption, consistent with the role of matriptase in regulating epithelial integrity. Surprisingly, MCoTI-II was unable to inhibit matriptase-dependent proteolytic activation of prostasin, a GPI-anchored serine protease also implicated in epithelial homeostasis. These observations suggest that the unusually high selectivity afforded by MCoTI-II and its biological effectiveness might represent a useful starting point for the development of therapeutic inhibitors, and further highlight the role of matriptase in epithelial maintenance.
Comparison of the effect of coagulation and platelet function
impairments on various mouse bleeding models
Authors: Vaezzadeh Nima , Ni Ran , Kim Paul Y. , Weitz Jeffrey I. , Gross Peter L. 
Published: April 2014

SummaryHaemostatic impairments are studied in vivo using one of several murine bleeding models. However it is not known whether these models are equally appropriate for assessing coagulation or platelet function defects. It was our study objective to assess the performance of arterial, venous and combined arterial and venous murine bleeding models towards impaired coagulation or platelet function. Unfractionated heparin (UFH) or αIIbβ3 inhibitory antibody (Leo.H4) were administered to mice, and their effects on bleeding in saphenous vein, artery, and tail tip transection models were quantified and correlated with their effects on plasma clotting and ADP-induced platelet aggregation, respectively. All models exhibited similar sensitivity with UFH (EC50 dose = 0.19, 0.13 and 0.07 U/g, respectively) (95% CI = 0.14 – 0.27, 0.08 – 0.20, and 0.03 – 0.16 U/g, respectively). Maximal inhibition of ex vivo plasma clotting could be achieved with UFH doses as low as 0.03 U/g. In contrast, the saphenous vein bleeding model was less sensitive to αIIbβ3 inhibition (EC50 = 6.9 µg/ml) than tail transection or saphenous artery bleeding models (EC50 = 0.12 and 0.37 µg/ml, respectively) (95% CI = 2.4 – 20, 0.05 – 0.33, and 0.06 – 2.2 µg/ml, respectively). The EC50 of Leo.H4 for ADP-induced platelet aggregation in vitro (8.0 µg/ml) was at least 20-fold higher than that of the tail and arterial, but not the venous bleeding model. In conclusion, venous, arterial and tail bleeding models are similarly affected by impaired coagulation, while platelet function defects have a greater influence in models incorporating arterial injury.
The coagulation system and its function in early immune defense
Authors: Poll Tom van der , Herwald Heiko 
Published: April 2014

SummaryBlood coagulation has a Janus-faced role in infectious diseases. When systemically activated, it can cause serious complications associated with high morbidity and mortality. However, coagulation is also part of the innate immune system and its local activation has been found to play an important role in the early host response to infection. Though the latter aspect has been less investigated, phylogenetic studies have shown that many factors involved in coagulation have ancestral origins which are often combined with anti-microbial features. This review gives a general overview about the most recent advances in this area of research also referred to as immunothrombosis.
Sensitivity, Specificity, and Sex Differences in Symptoms Reported on the 13‐Item Acute Coronary Syndrome Checklist
Authors: DeVon Holli A. , Rosenfeld Anne , Steffen Alana D. , Daya Mohamud 
Published: April 2014

Background

Clinical symptoms are part of the risk stratification approaches used in the emergency department (
ED
) to evaluate patients with suspected acute coronary syndromes (
ACS
). The objective of this study was to determine the sensitivity, specificity, and predictive value of 13 symptoms for a discharge diagnosis of
ACS
in women and men.

Methods and Results

The sample included 736 patients admitted to 4
ED
s with symptoms suggestive of
ACS
. Symptoms were assessed with the 13‐item validated
ACS
Symptom Checklist. Mixed‐effects logistic regression models were used to estimate sensitivity, specificity, and predictive value of each symptom for a diagnosis of
ACS
, adjusting for age, obesity, diabetes, and functional status. Patients were predominantly male (63%) and Caucasian (70.5%), with a mean age of 59.7±14.2 years. Chest pressure, chest discomfort, and chest pain demonstrated the highest sensitivity for
ACS
in both women (66%, 66%, and 67%) and men (63%, 69%, and 72%). Six symptoms were specific for a non‐
ACS
diagnosis in both women and men. The predictive value of shoulder (odds ratio [
OR]
=2.53; 95%
CI
=1.29 to 4.96) and arm pain (
OR
2.15; 95%
CI
=1.10 to 4.20) in women was nearly twice that of men (
OR
=1.11; 95%
CI
=0.67 to 1.85 and
OR
=1.21; 95%
CI
=0.74 to 1.99). Shortness of breath (
OR
=0.49; 95%
CI
=0.30 to 0.79) predicted a non‐
ACS
diagnosis in men.

Conclusions

There were more similarities than differences in symptom predictors of
ACS
for women and men.
The Possibility of Compensation for Damages in Cases of Wrongful Conception, Wrongful Birth and Wrongful Life. An Estonian Perspective
Authors: Sõritsa Dina , Lahe Janno 
Published: April 2014

Abstract
While case law in cases of wrongful conception, wrongful birth and wrongful life is completely missing in Estonia, this article is aimed at providing possible solutions under Estonian law to some of the legally complex problems that these cases contain. Through the analysis of Estonian, German and u.s. legal literature and case law, the article is mainly focused on proposing some solutions to the legal problems concerning compensable damage, but also explains the Estonian legal framework of the contractual and delictual basis for compensation for the damages. The application of several grounds for the possibility of limiting the compensation in the afore-mentioned cases are analysed.
The Case of the Electronic Cigarette in the EU
Authors: Syx Eugenie 
Published: April 2014

Abstract
Although the electronic cigarette was invented in 2004, only recently the product has started to provoke discussion. On the one hand, the electronic cigarette is characterized by scientific uncertainties. It is not clear whether the device can be used in smoking cessation therapy, whether the use induces non-smokers — including minors — to start smoking and whether the vaporized substances and the act of vaporizing itself (which is smoking an electronic cigarette) is harmful. On the other hand, there is no harmonised European legal framework and different Member States attribute a different legal status to the e-cigarette. In this article, the author analyses how the e-cigarette should be qualified according to the current European legislation and ecj case law and describes how the e-cigarette is qualified in the uk, France, the Netherlands, Belgium and Spain.
Giving Information on Medicinal Products to the General Public — In Search of a Definition to Safeguard the Patient
Authors: Faeh Andrea 
Published: April 2014

Abstract
Information on medicinal products is vital for enabling patients to give informed consent to the use of a specific product. Within the European Union (eu) the debate about how much information about prescription-only medicinal products should be made available to patients has gone on for the past five years with no definite conclusion yet. This contribution assesses the current legislation and the ongoing debate in order to identify the challenges and the prospect of new legislation, and consider its potential implications for the scope for advertising and for patient safety.
Nomenclatural observations on the genus “Bryopsidella” (Ulvophyceae, Bryopsidaceae)
Authors: Furnari Giovanni , CORMACI MARIO 
Published: April 2014

Feldmann (1970: 249), quoting the results of Hustede (1960), who had shown that Bryopsis halymeniae Berthold (1882: 497) was the gametophyte of a Derbesia sp.[1], pointed out that this species could not belong to the genus Bryopsis differing from it in chloroplasts with no pyrenoids and gametes without a stigma. On that basis, as well as because of its peculiar life cycle, he stated that Bryopsis halymeniae should be considered the type of a new genus: Bryopsidella. Even though Feldmann (1970) did not explicitely propose the new combination Bryopsidella halymeniae, such a binomial was reported by Gallardo et al. (1993: 412, note 60) and by Boudouresque & Per-ret-Boudoure-sque (1987: 83).[1]A more complete paper showing that Derbesia neglecta and Bryopsis halymeniae are phases of one species, was later published by Hustede (1964).
Trend of Surface Air Temperature in Eastern China and Associated Large-Scale Climate Variability over the Last 100 Years
Authors: Zhao Ping , Jones Phil , Cao Lijuan , Yan Zhongwei , Zha Shuyao , Zhu Yani , Yu Yu , Tang Guoli 
Published: April 2014

Abstract
Using the reconstructed continuous and homogenized surface air temperature (SAT) series for 16 cities across eastern China (where the greatest industrial developments in China have taken place) back to the nineteenth century, the authors examine linear trends of SAT. The regional-mean SAT over eastern China shows a warming trend of 1.52°C (100 yr)−1 during 1909–2010. It mainly occurred in the past 4 decades and this agrees well with the variability in another SAT series developed from a much denser station network (over 400 sites) across this part of China since 1951. This study collects population data for 245 sites (from these 400+ locations) and split these into five equally sized groups based on population size. Comparison of these five groups across different durations from 30 to 60 yr in length indicates that differences in population only account for between 9% and 24% of the warming since 1951. To show that a larger urbanization impact is very unlikely, the study additionally determines how much can be explained by some large-scale climate indices. Anomalies of large-scale climate indices such as the tropical Indian Ocean SST and the Siberian atmospheric circulation systems account for at least 80% of the total warming trends.
On the Relationship between ENSO, Stratospheric Sudden Warmings, and Blocking
Authors: Barriopedro David , Calvo Natalia 
Published: April 2014

Abstract
This paper examines the influence of El Niño–Southern Oscillation (ENSO) on different aspects of major stratospheric sudden warmings (SSWs), focusing on the precursor role of blocking events. The results reveal an ENSO modulation of the blocking precursors of SSWs. European and Atlantic blocks tend to precede SSWs during El Niño (EN), whereas eastern Pacific and Siberian blocks are the preferred precursors of SSWs during La Niña (LN) winters. This ENSO preference for different blocking precursors seems to occur through an ENSO effect on regional blocking persistence, which in turn favors the occurrence of SSWs. The regional blocking precursors of SSWs during each ENSO phase also have different impacts on the upward propagation of planetary-scale wavenumbers 1 and 2; hence, they determine ENSO differences in the wavenumber signatures of SSWs. SSWs occurring during EN are preceded by amplification of wavenumber 1, whereas LN SSWs are predominantly associated to wavenumber-2 amplification. However, there is not a strong preference for splitting or displacement SSWs during any ENSO phase. This is mainly because during EN, splitting SSWs do not show a wavenumber-2 pattern.
Evaluation of Assumptions in Soil Moisture Triple Collocation Analysis
Authors: Yilmaz M. Tugrul , Crow Wade T. 
Published: April 2014

Abstract
Triple collocation analysis (TCA) enables estimation of error variances for three or more products that retrieve or estimate the same geophysical variable using mutually independent methods. Several statistical assumptions regarding the statistical nature of errors (e.g., mutual independence and orthogonality with respect to the truth) are required for TCA estimates to be unbiased. Even though soil moisture studies commonly acknowledge that these assumptions are required for an unbiased TCA, no study has specifically investigated the degree to which errors in existing soil moisture datasets conform to these assumptions. Here these assumptions are evaluated both analytically and numerically over four extensively instrumented watershed sites using soil moisture products derived from active microwave remote sensing, passive microwave remote sensing, and a land surface model. Results demonstrate that nonorthogonal and error cross-covariance terms represent a significant fraction of the total variance of these products. However, the overall impact of error cross correlation on TCA is found to be significantly larger than the impact of nonorthogonal errors. Because of the impact of cross-correlated errors, TCA error estimates generally underestimate the true random error of soil moisture products.
Improving foster children’s school performance: a replication of the Helsingborg study
Authors: Tordön Rikard , Vinnerljung Bo , Axelsson Ulla 
Published: April 2014

A replication of the Helsingborg study (Tideman, et al., 2011) was conducted in the municipality of Norrköping in 2008–2011. Results confirm the conclusions from the original study that children in foster care can benefit from a working model aimed to improve school performance. Furthermore, a possible way to address poor numeracy skills by computerised working memory training was identified. Implications for further research in active interventions to address underachieving foster children are discussed.
To see, or not to see, that is the question: can public disclosure really improve transparency between medicine and the pharmaceutical industry?
Authors: Smith Geoffrey P 
Published: April 2014

Objective: To critically review the potential effect of the public reporting of pharmaceutical company payments to healthcare professionals on the relationship between medicine and industry. Method: This review is based on an examination of the ‘Transparency Model’ put out recently for consultation by Medicines Australia. Results: Public reporting in itself will neither sharpen the boundaries between medicine and the pharmaceutical industry nor restore public confidence. Conclusions: Focusing on payments for clinical research and on the larger payments to healthcare professionals would lead to a better understanding of the interplay between science and marketing.
Activity-based funding: implications for mental health services and consultation-liaison psychiatry
Authors: Wand Anne 
Published: April 2014

Objective: The aim of this paper is to inform mental health professionals about Activity-based funding (ABF) and the implications for data collection and clinical practice, in particular for consultation-liaison (CL) psychiatry. Conclusions: Activity-based funding may provide an opportunity for mental health services to be more equitably resourced, but much needs to be done to demonstrate that the funding model works in mental health. It is important to ensure that data collected is meaningful and accurate and reflects the diverse roles of mental health clinicians, including in CL. Inpatient and community services should be integrated in the model, as well as safeguards against potential abuse. Clinicians, in partnership with initiatives such as the Australian Mental Health Outcomes and Classification Network, are best placed to guide the development of an ABF system for mental health which appropriately recognises the complexity and variability between patients in different settings.
Successful foot salvage with microvascular flaps in diabetic patients
Authors: Eskelinen E. , Kaartinen I. , Kääriäinen M. , Kuokkanen H. 
Published: April 2014

Background and Aims: Complex nontraumatic foot lesions often lead to major lower-limb amputation in diabetic patients. We aimed to evaluate outcome of free flap transfer in such cases. Materials and Methods: A total of 11 consecutive diabetic patients, hospitalized between 2007 and 2012 at a university central hospital for a free flap transfer, were followed until September 2013. Amputation-free survival, patient survival, and complete wound healing were defined as primary endpoints. Healing time of tissue lesions was analyzed. All pre- and postoperative data were retrospectively collected from hospital charts. Results: Complete tissue healing at 6 and 12 months after free flap transfer were 55% (6/11) and 82% (9/11), respectively. The median time to complete tissue healing was 123 days (range, 45–207 days). Overall limb salvage, survival, and amputation-free survival rates at 12 months were 90%, 91%, and 82%, respectively. The clinically important endpoint, namely, amputation-free survival with completely healed wounds, was attained in 9 of 11 patients at 1 year. Conclusion: Free tissue transfer enables successful wound healing and limb salvage rather than amputation in selected diabetic patients with difficult-to-heal wounds. Complete healing of tissue lesions is slow even after successful surgery. Preoperative assessment of the condition of patients is the key to success.