bluuebunny/crossref_metadata_2025_split huggingface dataset:
Independent validation of the Enhanced Liver Fibrosis (ELF) score in the ANRS HC EP 23 Fibrostar cohort of patients with chronic hepatitis C
Authors: Guéchot Jérôme , Trocmé Candice , Renversez Jean-Charles , Sturm Nathalie , Zarski Jean-Pierre 
Published: April 2012

Abstract: The Enhanced Liver Fibrosis (ELF) score combining serum hyaluronan, N-terminal peptide of type III procollagen and tissue inhibitor of metalloproteinase-1, was reported as relevant in predicting liver fibrosis in chronic liver disease and proposed as an alternative to liver biopsy.: We evaluated the ELF score in a cohort of chronic hepatitis C (CHC) patients included in a multicenter prospective study (ANRS HC EP 23 Fibrostar) using commercial reagents, different from those developed by the manufacturer of the Siemens ELF™ test.: In 512 CHC, the ELF score, using ROC curves, showed good predictive performances for severe fibrosis [AUROC=0.82; 95% confidence interval (CI) 0.78–0.86]and for cirrhosis (AUROC=0.85; 95% CI 0.81–0.90), but slightly lower for significant fibrosis (AUROC=0.78; 95% CI 0.74–0.82). The Obuchowski measure (0.81) showed that the ELF score globally performed as a marker of liver fibrosis. The ELF score predicted significant fibrosis (cut-off=9.0) with a sensitivity of 0.86, a specificity of 0.62, a positive predictive value (PPV) of 0.80 and a negative predictive value (NPV) of 0.70. For extensive fibrosis (cut-off=9.33), sensitivity was 0.90, specificity was 0.63, PPV was 0.73 and NPV was 0.85. For cirrhosis (cut-off=9.35), sensitivity was 0.83, specificity was 0.75, PPV was 0.44 and NPV was 0.95.: This study confirms the ELF score performance as an index to predict liver fibrosis or cirrhosis in CHC. The ELF test, using validated reagents, could be added to the health authorities approved non-invasive tests in assessing fibrosis as surrogate to liver biopsy.
Interference of the new oral anticoagulant dabigatran with frequently used coagulation tests
Authors: Halbmayer Walter-Michael , Weigel Guenter , Quehenberger Peter , Tomasits Josef , Haushofer Alexander C. , Aspoeck Gerold , Loacker Lorin , Schnapka-Koepf Mirjam , Goebel Georg , Griesmacher Andrea 
Published: April 2012

AbstractDabigatran etexilate is a new oral anticoagulant for the therapy and prophylaxis of venous thromboembolism and stroke prevention in patients with atrial fibrillation. To investigate the extent of interactions of this new anticoagulant with frequently used coagulation assays, we completed a multicenter in vitro trial with Conformité Européenne(CE)-labeled dabigatran-spiked plasma samples.Lyophilized plasma samples with dabigatran concentrations ranging from 0.00 to 0.48 μg/mL were sent to the coagulation laboratories of six major Austrian hospitals for evaluation. Coagulation assays were performed under routine conditions using standard reagents and analyzer.Dabigatran led to a dose-dependent prolongation of the clotting times in coagulometric tests and influenced the majority of the parameters measured. Statistically significant interference could be observed with the prothrombin time (PT), activated partial thromboplastin time (aPTT) and PT/aPTT-based assays (extrinsic/intrinsic factors, APC-resistance test) as well as lupus anticoagulant testing. Even non-clotting tests, such as the colorimetric factor XIII activity assay and to a minor extent the amidolytic antithrombin activity assay (via factor IIa) were affected.This multicenter trial confirms and also adds to existing data, demonstrating that laboratories should expect to observe strong interferences of coagulation tests with increasing concentrations of dabigatran. This finding might become particularly important in the elderly and in patients with renal impairment as well as patients whose blood is drawn at peak levels of dabigatran.
Validation of a new generation POCT glucose device with emphasis on aspects important for glycemic control in the hospital care
Authors: Kos Snježana , van Meerkerk Arie , van der Linden Joke , Stiphout Theo , Wulkan Remi 
Published: April 2012

AbstractPoint-of-care (POC) glucose devices are widely used for insulin-dosage decision-making although such an application is not always permitted. In this study, we have evaluated a new generation of POC glucose device, the HemoCueThis study was performed according to the CLSI/STARD criteria. The 201DMRT was compared to the laboratory hexokinase glucose method (Siemens Dimension VistaThe 201DMRT showed a good agreement with the laboratory reference method. This was examined using Deming regression analysis, percentage Bland-Altman plot and a modified Clarke-error grid. The total analytical error at the clinically critical glucose concentrations of 5.6, 7.0 and 11.1 mmol/L (101, 126 and 200 mg/dL) was 6.4%, 4.3% and 3.0%, respectively. The total error among the different POC devices and among different cuvette lot numbers was <6.5%. Glucose measurements on the 201DMRT were not affected by changes in partial pressure of oxygen, whereas changes in hematocrit had influence on the results (3.4% for every 0.10 L/L change in hematocrit).The 201DMRT device can be used for glycemic control based on analytical results presented. However, the clinical applicability for tight glycemic control must be confirmed in a clinical study.
γ′ Fibrinogen as a novel marker of thrombotic disease
Authors: Farrell David H. 
Published: April 2012

Abstract
γ′ Fibrinogen is an isoform of fibrinogen that normally constitutes about 7% of total plasma fibrinogen, and arises from an alternative processing event in the γ chain mRNA. γ′ Fibrinogen is a newly-emerging cardiovascular disease (CVD) risk factor that appears to have an independent association with CVD from that of total fibrinogen, which is itself a well-established CVD risk factor. γ′ Fibrinogen shows a significant association with coronary artery disease and myocardial infarction in at least four case-control studies, including the Stockholm Coronary Artery Risk Factor study and the Framingham Heart Study. γ′ Fibrinogen is also significantly associated with stroke, as shown in the Erasmus Stroke Study and others. The role of genetic polymorphisms in the association between γ′ fibrinogen and CVD is under active investigation. γ′ Fibrinogen increases during inflammation, and is differentially regulated from total fibrinogen under pathologic conditions, as demonstrated in the Periodontitis and Vascular Events study. The association between γ′ fibrinogen and venous thromboembolism remains unclear, however, with some studies showing an inverse association with γ′ fibrinogen levels and other studies showing the opposite.
The role of red blood cell distribution width in cardiovascular and thrombotic disorders
Authors: Montagnana Martina , Cervellin Gianfranco , Meschi Tiziana , Lippi Giuseppe 
Published: April 2012

AbstractThe red blood cell (RBC) distribution width (RDW) is a measurement of the size variation as well as an index of the heterogeneity of the erythrocytes (i.e., anysocytosis), which is typically used in combination with the mean corpuscular volume to troubleshoot the cause of an underlying anemia. Reliable data emerged from a variety of clinical studies have, however, disclosed a new and unpredictable scenario in the clinical usefulness of this measure, supporting the hypothesis that RDW might be a useful parameter for gathering meaningful clinical information, either diagnostic or prognostic, on a variety of cardiovascular and thrombotic disorders. Highly significant associations have been described between RDW value and all-cause, non-cardiac and cardiac mortality in patients with coronary artery disease, acute and chronic heart failure, peripheral artery disease, stroke, pulmonary embolism and pulmonary arterial hypertension. It is however still unclear whether anysocytosis might be the cause, or a simple epiphenomenon of an underlying disease, such as inflammation, impaired renal function, undernutrition, oxidative damage, or perhaps an element of both. Nevertheless, RDW is an easy, inexpensive, routinely reported test, whose assessment might allow the acquisition of significant diagnostic and prognostic information in patients with cardiovascular and thrombotic disorders.
Percentage of hypochromic erythrocytes as a potential marker of iron availability
Authors: Urrechaga Eloísa , Borque Luís , Escanero Jesús F. 
Published: April 2012

AbstractThe percentage of hypochromic red cells (% Hypo-He) is now available on the Sysmex analyzer XE 5000 (Sysmex Corporation, Kobe, Japan). In this study the reliability of % Hypo-He in the assessment of iron status in the presence of inflammation is investigated.Ninety healthy subjects, 91 patients with iron deficiency anemia (IDA) previous to therapy, 65 patients with chronic kidney disease (CKD), 57 patients with anemia of chronic diseases (ACD) and 28 patients with storage iron deficiency (ACD/IDA) receiving therapy were analyzed. Pearson’s correlation, Independent samples t-test, receiver operating characteristic (ROC) curve analysis and Cohen’s k index were applied.% Hypo-He values inversely correlated with the blood hemoglobin (Hb) (r=–0.78) and Hb content (MHC, r=–0.75). In patients with IDA and ACD/IDA the values obtained for % Hypo-He showed no statistical difference (p=0.5037). ROC analysis results for % Hypo-He in the detection of iron deficiency defined by a serum transferrin receptor (sTfR) >21 nmol/L. The area under the curve is 0.929; cut-off 3.6%, sensitivity 91.5% and specificity 80.9%. Using the threshold 3.6% the k index obtained in comparison to sTfR was 0.64.% Hypo-He is a reliable parameter for the detection of iron deficiency in patients with anemia in the presence of inflammation.
Characterization of SPINK9, a KLK5-specific inhibitor expressed in palmo-plantar epidermis
Authors: Brännström Kristoffer , Öhman Anders , von Pawel Rammingen Ulrich , Olofsson Anders , Brattsand Maria 
Published: April 2012

Abstract
SPINK9, a Kazal-type serine protease inhibitor, is almost exclusively expressed in the palmo-plantar epidermis. SPINK9 selectively inhibits kallikrein-related peptidase 5 (KLK5), no other target enzyme is known at present. In this study, we defined the reactive loop to residues 48 and 49 of SPINK9 and characterized the inhibition and binding of different SPINK9 variants towards KLK5, KLK7, KLK8 and KLK14. Substitutions of single amino acids in the reactive loop had a large impact on both inhibitory efficiency and specificity. Binding studies showed that it is mainly the dissociation rate that is affected by the amino acid substitutions. The inhibitory effect of wild-type SPINK9 was clearly pH-dependent with an improved effect at a pH similar to that of the outer layers of the skin. Modeling of the enzyme-inhibitor complexes showed that the reactive loop of SPINK9 fits very well into the deep negatively charged binding pocket of KLK5. A decrease in pH protonates His48 of the wild-type protein resulting in a positively charged residue, thereby explaining the observed decreased dissociation rate. Interestingly, substitution with a positively charged amino acid at position 48 resulted in a more efficient inhibitor at higher pH.
Kallikrein 6 is a novel molecular trigger of reactive astrogliosis
Authors: Scarisbrick Isobel A. , Radulovic Maja , Burda Joshua E. , Larson Nadya , Blaber Sachiko I. , Giannini Caterina , Blaber Michael , Vandell Alexander G. 
Published: April 2012

Abstract
Kallikrein-related peptidase 6 (KLK6) is a trypsin-like serine protease upregulated at sites of central nervous system (CNS) injury, including de novo expression by reactive astrocytes, yet its physiological actions are largely undefined. Taken with recent evidence that KLK6 activates G-protein-coupled protease-activated receptors (PARs), we hypothesized that injury-induced elevations in KLK6 contribute to the development of astrogliosis and that this occurs in a PAR-dependent fashion. Using primary murine astrocytes and the Neu7 astrocyte cell line, we show that KLK6 causes astrocytes to transform from an epitheliod to a stellate morphology and to secrete interleukin 6 (IL-6). By contrast, KLK6 reduced expression of glial fibrillary acidic protein (GFAP). The stellation-promoting activities of KLK6 were shown to be dependent on activation of the thrombin receptor, PAR1, as a PAR1-specific inhibitor, SCH79797, blocked KLK6-induced morphological changes. The ability of KLK6 to promote astrocyte stellation was also shown to be linked to activation of protein kinase C (PKC). These studies indicate that KLK6 is positioned to serve as a molecular trigger of select physiological processes involved in the development of astrogliosis and that this is likely to occur at least in part by activation of the G-protein-coupled receptor, PAR1.
One round of SELEX for the generation of DNA aptamers directed against KLK6
Authors: Arnold Steve , Pampalakis Georgios , Kantiotou Kalliopi , Silva Dilson , Cortez Celia , Missailidis Sotiris , Sotiropoulou Georgia 
Published: April 2012

Abstract
Kallikrein-related peptidase 6 (KLK6) is an active serine protease that has been implicated in common pathologies, including neurodegenerative disorders such as Parkinson and Alzheimer disease and certain types of cancer. Antibodies, either polyclonal or monoclonal, that exhibit specificity for distinct members of the extended kallikrein family, including KLK6, were developed. With the exception of KLK3/PSA, the identification and generation of aptamers, as potential new tools with improved characteristics demanded for therapeutic and diagnostic applications, has not been explored for KLKs. Here, we report for the first time the identification of novel DNA aptamers against KLK6 that were isolated using a modified systemic evolution of ligands by exponential enrichment technique. The identified aptamers were characterized using fluorescence spectroscopy, competition ELISA, and quartz crystal microbalance, and two aptamers (008 and 022) were found to exhibit high affinity (K
d in the low nanomolar range) for KLK6. Aptamers were tested for their ability to bind to serum albumin, to demonstrate their specificity for their target, and the possible involvement of such proteins in the transport of aptamers into the bloodstream. The developed aptamers are expected to assist the development of novel diagnostic, biosensing, and therapeutic strategies.
Stromal cell-associated expression of kallikrein-related peptidase 6 (KLK6) indicates poor prognosis of ovarian cancer patients
Authors: Seiz Lina , Dorn Julia , Kotzsch Matthias , Walch Axel , Grebenchtchikov Nicolai I. , Gkazepis Apostolos , Schmalfeldt Barbara , Kiechle Marion , Bayani Jane , Diamandis Eleftherios P. , Langer Rupert , Sweep Fred C.G.J. , Schmitt Manfred , Magdolen Viktor 
Published: April 2012

Abstract
Several members of the human kallikrein-related peptidase family, including KLK6, are up-regulated in ovarian cancer. High KLK6 mRNA or protein expression, measured by quantitative polymerase chain reaction and enzyme-linked immunoassay, respectively, was previously found to be associated with a shortened overall and progression-free survival (OS and PFS, respectively). In the present study, we aimed at analyzing KLK6 protein expression in ovarian cancer tissue by immunohistochemistry. Using a newly developed monospecific polyclonal antibody, KLK6 immunoexpression was initially evaluated in normal tissues. We observed strong staining in the brain and moderate staining in the kidney, liver, and ovary, whereas the pancreas and the skeletal muscle were unreactive, which is in line with previously published results. Next, both tumor cell- and stromal cell-associated KLK6 immunoexpression were analyzed in tumor tissue specimens of 118 ovarian cancer patients. In multivariate Cox regression analysis, only stromal cell-associated expression, besides the established clinical parameters FIGO stage and residual tumor mass, was found to be statistically significant for OS and PFS [high vs. low KLK6 expression; hazard ratio (HR), 1.92; p=0.017; HR, 1.80; p=0.042, respectively]. These results indicate that KLK6 expressed by stromal cells may considerably contribute to the aggressiveness of ovarian cancer.
The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness
Authors: Lose Felicity , Lawrence Mitchell G. , Srinivasan Srilakshmi , O’Mara Tracy , Marquart Louise , Chambers Suzanne , Gardiner Robert A. , Aitken Joanne F. , Spurdle Amanda B. , Batra Jyotsna , Clements Judith A. 
Published: April 2012

Abstract
Kallikrein 14 (KLK14) has been proposed as a useful prognostic marker in prostate cancer, with expression reported to be associated with tumour characteristics such as higher stage and Gleason score. KLK14 tumour expression has also shown the potential to predict prostate cancer patients at risk of disease recurrence after radical prostatectomy. The KLKs are a remarkably hormone-responsive family of genes, although detailed studies of androgen regulation of KLK14 in prostate cancer have not been undertaken to date. Using in vitro studies, we have demonstrated that unlike many other prostatic KLK genes that are strictly androgen responsive, KLK14 is more broadly expressed and inversely androgen regulated in prostate cancer cells. Given these results and evidence that KLK14 may play a role in prostate cancer prognosis, we also investigated whether common genetic variants in the KLK14 locus are associated with risk and/or aggressiveness of prostate cancer in approximately 1200 prostate cancer cases and 1300 male controls. Of 41 single nucleotide polymorphisms assessed, three were associated with higher Gleason score (≥7): rs17728459 and rs4802765, both located upstream of KLK14, and rs35287116, which encodes a p.Gln33Arg substitution in the KLK14 signal peptide region. Our findings provide further support for KLK14 as a marker of prognosis in prostate cancer.
Epigenetic regulation of kallikrein-related peptidases: there is a whole new world out there
Authors: Pasic Maria D. , Olkhov Ekaterina , Bapat Bharati , Yousef George M. 
Published: April 2012

Abstract
The human kallikreins are a cluster of 15 kallikreins and kallikrein-related peptidases (KLKs). Evidence shows the involvement of KLKs in a wide range of pathophysiological processes, and underscores their potential contribution to cancer, skin and neurodegenerative disorders. The control of KLK expression is not fully elucidated. Understanding the mechanisms controlling KLK expression is an essential step towards exploring the pathogenesis of several diseases and the use of KLKs as disease biomarkers and/or therapeutic targets. Recently, epigenetic changes (including methylation, histone modification and microRNAs [miRNAs]) have drawn attention as a new dimension for controlling KLK expression. Reports showed the effect of methylation on the expression of KLK genes. This was also shown to have potential utility as a prognostic marker in cancer. miRNAs are small RNAs that control the expression of their targets at the post-transcriptional level. Target prediction showed that KLKs are potential targets of miRNAs that are dysregulated in tumors, including prostate, kidney and ovarian cancers, with downstream effect on tumor proliferation. Experimental validation remains an essential step to confirm the KLK-miRNA interaction. Epigenetic regulation of KLKs holds promise for an array of therapeutic applications in many diseases including cancer.
Immunosuppressive Regimen and Interstitial Fibrosis and Tubules Atrophy at 12 Months Postrenal Transplant
Authors: Gelens Mariëlle A.C.J. , Steegh Floor M.E.G. , van Hooff Johannes P. , Jan van Suylen Robert , Nieman Frederikus H.M. , van Heurn Lodewijk W.E. , Peutz-Kootstra Carine J. , Christiaans Maarten H.L. 
Published: April 2012

Summary

Background and objectives
Chronic renal transplant dysfunction is histopathologically characterized by interstitial fibrosis and tubular atrophy. This study investigated the relative contribution of baseline donor, recipient, and transplant characteristics to interstitial fibrosis and tubular atrophy score at month 12 after renal transplantation.

Design, setting, participants, & measurements
This retrospective study includes all 109 consecutive recipients with adequate implantation and month 12 biopsies transplanted between April of 2003 and February of 2007. Immunosuppression regimen was tacrolimus and steroids (10 days) plus either sirolimus or mycophenolate mofetil.

Results
Average interstitial fibrosis and tubular atrophy score increased from 0.70 to 1.65 (P<0.001). In an adjusted multiple linear regression analysis, interstitial fibrosis and tubular atrophy score at month 12 was significantly related to donor type (donors after cardiac death versus living donor had interstitial fibrosis and tubular atrophy score+0.41, 95% confidence interval=0.05–0.76, P=0.02), baseline interstitial fibrosis and tubular atrophy, and immunosuppression regimen. Because of interaction between the latter two variables (P=0.002), results are given separately: recipients with a baseline interstitial fibrosis and tubular atrophy score of zero had a 0.60 higher score at month 12 (95% confidence interval=0.09–1.10, P=0.02) when mycophenolate mofetil-treated, whereas recipients with a baseline interstitial fibrosis and tubular atrophy score more than zero had a 0.38 higher score at month 12 (95% confidence interval=0.01–0.74, P=0.04) when sirolimus-treated. A higher score at month 12 correlated with a lower estimated GFR (ρ=−0.45, P<0.001).

Conclusions
These findings suggest that histologic assessment of a preimplantation biopsy may guide choice of immunosuppresion to maximize transplant survival and its interaction with type of immunosuppression.
Osteoprotegerin/RANKL Axis and Progression of Coronary Artery Calcification in Hemodialysis Patients
Authors: Ozkok Abdullah , Caliskan Yasar , Sakaci Tamer , Erten Gaye , Karahan Gonca , Ozel Alper , Unsal Abdulkadir , Yildiz Alaattin 
Published: April 2012

Summary

Background and objectives
Vascular calcification is associated with increased cardiovascular mortality in chronic hemodialysis patients. This prospective study investigated the relationship between serum osteoprotegerin, receptor activator of NF-κB ligand, inflammatory markers, and progression of coronary artery calcification score.

Design, setting, participants, & measurements
Seventy-eight hemodialysis patients were enrolled. Serum IL-1β, IL-6, TNF-α, osteoprotegerin, receptor activator of NF-κB, fetuin A, and bone alkaline phosphatase were measured by ELISA. Coronary artery calcification score was measured two times with 1-year intervals, and patients were classified as progressive or nonprogressive.

Results
Baseline and first-year serum osteoprotegerin levels were significantly higher in the progressive than nonprogressive group (17.39±9.67 versus 12.90±6.59 pmol/L, P=0.02; 35.17±18.35 versus 24±11.65 pmol/L, P=0.002, respectively). The ratio of serum osteoprotegerin to receptor activator of NF-κB ligand at 1 year was significantly higher in the progressive group (0.26 [0.15–0.46] versus 0.18 [0.12–0.28], P=0.004). Serum osteoprotegerin levels were significantly correlated with coronary artery calcification score at both baseline (r=0.36, P=0.001) and 1 year (r=0.36, P=0.001). Importantly, progression in coronary artery calcification score significantly correlated with change in serum osteoprotegerin levels (r=0.39, P=0.001). In addition, serum receptor activator of NF-κB ligand levels were significantly inversely correlated with coronary artery calcification scores at both baseline (r=−0.29, P=0.01) and 1 year (r=−0.29, P=0.001). In linear regression analysis for predicting coronary artery calcification score progression, only baseline coronary artery calcification score and change in osteoprotegerin were retained as significant factors in the model.

Conclusions
Baseline coronary artery calcification score and serum osteoprotegerin levels were significantly associated with progression of coronary artery calcification score in hemodialysis patients.