bluuebunny/crossref_metadata_2025_split huggingface dataset:
Function of eltrombopag-induced platelets compared to platelets from control patients with immune thrombocytopenia
Authors: Haselboeck Johanna , Kaider Alexandra , Pabinger Ingrid , Panzer Simon 
Published: February 2013

SummaryData on the in vivo function of platelets induced by the thrombopoietin receptor agonist eltrombopag are scarce. To assess a possible influence of eltrombopag we compared platelet function of eltrombopag-treated immune thrombocytopenia (ITP) patients (group 1; n=10) after treatment response to that from control ITP patients (group 2; n=12). We further analysed platelet function at baseline and after one, three, and four weeks of eltrombopag treatment and estimated daily changes of platelet function during the eltrombopag-induced platelet rise. The formation of platelet-monocyte aggregates (PMA), P-selectin expression [MFI], and platelet adhesion under high shear conditions (surface coverage, SC) in vivo and after in vitro addition of agonists (ADP, TRAP-6, Collagen) were similar between both groups after response to eltrombopag treatment. Only TRAP-6 induced a lower SC in the eltrombopag group (p=0.03). All platelet function parameters except for Collagen-induced P-selectin expression changed significantly during treatment with eltrombopag. PMA, naïve and after addition of ADP or TRAP-6 increased with increasing platelet counts. P-selectin expression decreased, when measured without and upon addition of ADP, increased in the presence of TRAP-6, and remained unchanged after addition of Collagen. SC increased during the eltrombopag-induced platelet rise. All significant changes of platelet function correlated to changes in platelet counts. Two patients developed venous thromboses during eltrombopag treatment, but no association with any distinct single platelet function parameter or combinations thereof was identifiable. Thus, eltrombopag-induced platelets function similar to those from control ITP patients without discernible increased hyper-reactivity.
Effective elimination of dabigatran by haemodialysis
Authors: Formella Stephan , Wiegert Erol , Moschetti Viktoria , Slowinski Torsten , Neumayer Hans-H. , Liesenfeld Karl-Heinz , Lehr Thorsten , Härtter Sebastian , Friedman Jeffrey , Khadzhynov Dmytro , Wagner Frank , Peters Harm , Clemens Andreas 
Published: February 2013

SummaryDabigatran, a specific, reversible direct thrombin inhibitor, is used to prevent ischaemic and haemorrhagic strokes in patients with atrial fibrillation. As with every anticoagulant, there is a need to rapidly reverse its effects in emergency situations. In an open-label, single-centre phase I study with two fixed multiple dosing periods, we investigated the pharmacokinetics, pharmacodynamics and safety of dabigatran before, during and after 4 hour haemodialysis sessions with either 200 or 400 ml/min targeted blood flow in seven end-stage renal disease patients without atrial fibrillation. Dabigatran was administered over three days in a regimen designed to achieve peak plasma concentrations comparable to those observed in atrial fibrillation patients receiving 150 mg b.i.d. and to attain adequate distribution of dabigatran in the central and peripheral compartments. Plasma concentration-time profiles were similar in both periods on Day 3 (Cmax: 176 and 159 ng/ml). Four hours of haemodialysis removed 48.8% and 59.3% of total dabigatran from the central compartment with 200 and 400 ml/minute targeted blood flow, respectively. The anticoagulant activity of dabigatran was linearly related to its plasma levels. There was a minor redistribution of dabigatran (<16%) after the end of the haemodialysis session. In conclusion, a 4 hour haemodialysis session can rapidly eliminate a substantial amount of dabigatran from the central compartment with a concomitant marked reduction in its anticoagulant activity. There was a clinically negligible redistribution of dabigatran after haemodialysis. These results demonstrate that haemodialysis can be a suitable approach to eliminate dabigatran in emergency situations.
Cellular and molecular regulation of vascular permeability
Authors: Goddard Lauren , Iruela-Arispe Luisa 
Published: February 2013

SummaryVascular permeability is a highly coordinated process that integrates vesicular trafficking, complex junctional rearrangements, and refined cytoskeletal dynamics. In response to the extracellular environment, these three cellular activities have been previously assumed to work in parallel to regulate the passage of solutes between the blood and tissues. New developments in the area of vascular permeability, however have highlighted the interdependence between trans- and para-cellular pathways, the cross-communication between adherens and tight junctions, and the instructional role of pericytes on endothelial expression of barrier-related genes. Additionally, significant effort has been placed in understanding the molecular underpinings that contribute to barrier restoration following acute permeability events and in clarifying the importance of context-dependent signaling initiated by permeability mediators. Finally, recent findings have uncovered an unpredicted role for transcription factors in the coordination of vascular permeability and clarified how junctional complexes can transmit signals to the nucleus to control barrier function. The goal of this review is to provide a concise and updated view of vascular permeability, discuss the most recent advances in molecular and cellular regulation, and introduce integrated information on the central mechanisms involved in trans-endothelial transport.
Expression and functional characterisation of natural R147W and K150del variants of protein C in the Chinese population
Authors: Ding Qiulan , Yang Likui , Hassanian Seyed , Rezaie Alireza R. 
Published: February 2013

SummaryProtein C is a vitamin K-dependent serine protease zymogen in plasma which upon activation to activated protein C (APC) by thrombin down-regulates the clotting cascade by limited proteolysis of the pro-coagulant cofactors Va and VIIIa. In addition to its anticoagulant activity, APC also exhibits potent cytoprotective and anti-inflammatory activities. While the anticoagulant activity of APC is enhanced by the cofactor function of protein S on membrane phospholipids, the cytoprotective intracellular signalling activity of APC requires complex formation with endothelial protein C receptor (EPCR) expressed on the vascular endothelium. Two natural variants of APC [Arg-147 to Trp substitution (R147W) and Lys-150 deletion (K150del)] have been identified in the Chinese population as hotspot mutants occurring with high frequencies of 27.8% and 13.9%, respectively, among 36 protein C-deficient subjects. The affected individuals exhibit variable thrombotic tendencies. To understand the underlying cause of the thrombotic phenotype in these patients, we expressed these two protein C variants in mammalian cells and characterised their anticoagulant and anti-inflammatory properties using established in vitro and cellular assays. Our results suggest that both R147W and K150del variants have normal amidolytic and proteolytic activities in the absence of cofactors. However, the R147W mutant exhibits ∼3 times lower affinity for binding to EPCR and the K150del variant has ∼2–3-fold impaired anticoagulant activity in the presence of protein S. These results provide some insight into the possible pathogenic mechanism of protein C deficiency in Chinese patients carrying these mutations.
Adrenal haemorrhage due to heparin-induced thrombocytopenia
Authors: Ketha Siva , Smithedajkul Patrick , Vella Adrian , Pruthi Rajiv , Wysokinski Waldemar , McBane Robert 
Published: February 2013

SummaryAdrenal haemorrhage (AH) is a rare but potentially devastating complication of heparin-induced thrombocytopenia (HIT). Neither the prevalence nor the natural history of AH due to HIT are known. The objectives of this study were to identify the spectrum of AH causes, to characterise the frequency of AH due to HIT and determine the natural history of HIT-associated AH. All patients with incident adrenal haemorrhage from January 2002 through June 2012 seen at the Mayo Clinic were identified. Over this time frame, there were a total of 115 patients with AH of which 11 cases (10%; mean age 67 ± 8 years; 73% female) were associated with HIT. Of these, all but one occurred in the postoperative setting and involved both adrenal glands (89%) with acute adrenal insufficiency at the time of diagnosis. Cases were found incidentally during an evaluation for fever, shock, abdominal pain or mental status changes. All HIT patients experienced venous thrombosis at other locations including deep venous thromboses (n=14), pulmonary emboli (n= 4) and arterial thrombosis (n=2). Four patients undergoing total knee arthroplasty had “spontaneous HIT” with AH in the absence of identifiable heparin exposure. Other causes of AH included trauma (29%), sepsis (15%), antiphospholipid antibody syndrome (10%), and metastatic disease (12%). In conclusion, AH is an important but seldom recognised presumed thrombotic complication of HIT, which usually occurs in the postoperative period, especially after orthopaedic procedures. This syndrome can occur in the apparent absence of heparin exposure, especially following major joint replacement surgery.
Calmodulin Mutations Associated With Recurrent Cardiac Arrest in Infants
Authors: Crotti Lia , Johnson Christopher N. , Graf Elisabeth , De Ferrari Gaetano M. , Cuneo Bettina F. , Ovadia Marc , Papagiannis John , Feldkamp Michael D. , Rathi Subodh G. , Kunic Jennifer D. , Pedrazzini Matteo , Wieland Thomas , Lichtner Peter , Beckmann Britt-Maria , Clark Travis , Shaffer Christian , Benson D. Woodrow , Kääb Stefan , Meitinger Thomas , Strom Tim M. , Chazin Walter J. , Schwartz Peter J. , George Alfred L. 
Published: February 2013

Background—
Life-threatening disorders of heart rhythm may arise during infancy and can result in the sudden and tragic death of a child. We performed exome sequencing on 2 unrelated infants presenting with recurrent cardiac arrest to discover a genetic cause.

Methods and Results—

We ascertained 2 unrelated infants (probands) with recurrent cardiac arrest and dramatically prolonged QTc interval who were both born to healthy parents. The 2 parent-child trios were investigated with the use of exome sequencing to search for de novo genetic variants. We then performed follow-up candidate gene screening on an independent cohort of 82 subjects with congenital long-QT syndrome without an identified genetic cause. Biochemical studies were performed to determine the functional consequences of mutations discovered in 2 genes encoding calmodulin. We discovered 3 heterozygous de novo mutations in either
CALM1
or
CALM2
, 2 of the 3 human genes encoding calmodulin, in the 2 probands and in 2 additional subjects with recurrent cardiac arrest. All mutation carriers were infants who exhibited life-threatening ventricular arrhythmias combined variably with epilepsy and delayed neurodevelopment. Mutations altered residues in or adjacent to critical calcium binding loops in the calmodulin carboxyl-terminal domain. Recombinant mutant calmodulins exhibited several-fold reductions in calcium binding affinity.

Conclusions—
Human calmodulin mutations disrupt calcium ion binding to the protein and are associated with a life-threatening condition in early infancy. Defects in calmodulin function will disrupt important calcium signaling events in heart, affecting membrane ion channels, a plausible molecular mechanism for potentially deadly disturbances in heart rhythm during infancy.
Recipient IL-6-572C/G genotype is associated with reduced incidence of acute rejection following liver transplantation
Authors: Yao Jia , Feng Xiao-Wen , Yu Xiao-Bo , Xie Hai-Yang , Zhu Li-Xian , Yang Zhe , Wei Ba-Jin , Zheng Shu-Sen , Zhou Lin 
Published: February 2013

Objective Acute rejection resulting from alloimmune responses is a major risk factor affecting patient survival following liver transplantation. Since interleukin (IL)-6 can mediate acute rejection, the association between IL-6 gene single nucleotide polymorphisms (SNPs) and incidence of acute rejection in liver transplant recipients was investigated. Methods Patients who received liver transplant between January 2005 and December 2010 were typed for IL6-572C/G (rs1800796) polymorphisms using the snapshot technique. Association between genotype and acute rejection was analysed using the SNP Statistics website: http://bioinfo.iconcologia.net/snpstats/start.htm . Allelic and genotypic distributions for rs1800796 were compared among 335 patients with or without acute rejection within the first 6 months following liver transplant. Results Incidence of acute rejection was 11.94%. A heterozygous CG genotype for IL6-572C/G was associated with a lower acute rejection rate compared with homozygous CC or GG genotypes. Conclusion IL6-572 CG genotype may be related to protection from acute rejection following liver transplant in Han Chinese patients.
The Biomechanical Effects of 1.0 to 1.2 Mrad of Gamma Irradiation on Human Bone–Patellar Tendon–Bone Allografts
Authors: Yanke Adam B. , Bell Rebecca , Lee Andrew , Kang Richard W. , Mather Richard C. , Shewman Elizabeth F. , Wang Vincent M. , Bach Bernard R. 
Published: February 2013

Background: Recent data suggest that anterior cruciate ligament (ACL) reconstruction with irradiated allograft tissue may lead to increased failure rates. Hypothesis: Low-dose (1.0-1.2 Mrad) gamma irradiation does not significantly alter the preimplantation biomechanical properties of bone–patellar tendon–bone (BTB) allografts. Study Design: Controlled laboratory study. Methods: Cyclic and failure mechanical properties were evaluated for 20 paired central-third human BTB allografts, with and without 1.0 to 1.2 Mrad of gamma irradiation. Testing included cyclic loading at 0.5 Hz for 100 cycles from 50 to 200 N and failure testing at a strain rate of 10% per second. Results: Cyclic elongation did not change significantly ( P = .151) with irradiation, increasing from a mean ± SD of 9.4 ± 2.1 mm to 11.3 ± 3.4 mm. Cyclic creep strain approached a significant increase with irradiation (1.3% ± 0.8% to 2.6% ± 1.5%; P = .076). Failure testing was not affected with irradiation with regard to maximum load (1680 ± 417 mm to 1494 ± 435 mm), maximum stress (40.8 ± 10.6 MPa to 37.5 ± 15.7 MPa), elongation (7.85 ± 1.35 mm to 8.67 ± 2.05 mm), or strain at maximum stress (0.158 ± 0.03 to 0.175 ± 0.03). Graft stiffness significantly decreased by 20% with irradiation (278 ± 67 N/mm to 221 ± 50 N/mm; P = .035). Conclusion: Low-dose (1.0-1.2 Mrad) gamma irradiation decreases BTB graft stiffness by 20%, but it does not affect other failure or cyclic parameters. Clinical Relevance: Aside from graft stiffness during load to failure testing, low-dose (1.0-1.2 Mrad) gamma irradiation of central-third human BTB allografts is not deleterious to preimplantation biomechanical properties.
Electrical application of polyamide reinforced with old tire rubber (ground tire rubber)
Authors: Mujal-Rosas R , Orrit-Prat J , Ramis-Juan X , Marin-Genesca M 
Published: February 2013

Mass production of tires and their subsequent storage after use is a serious environmental problem that is tried to be solved in various ways. One of these ways is the mixture of these old used tires (ground tire rubber (GTR)) with various thermoplastic and thermostable polymers. These blends are made by modifying the pretreatment the GTR is subjected to, the degree of devulcanization, the mixing or pressing conditions, etc. Later the mixtures are analyzed structurally and mechanically, looking for possible industrial applications for them. The present work aims to obtain materials suitable for the electric industry from the mixture of polyamide with old used tires (GTR), starting from the requirement of minimum recycling costs, that is using vulcanized GTR without any prior treatment but acting on the particle sizes with a simple and inexpensive screening. A novelty of this study is the large number of compounds analyzed, and the deep analysis these have been submitted to dielectric, mechanical, thermal and microstructure analyses to get a large number of variables in each test. Compounds were categorized as the three GTR particle sizes ( p < 200 μm, 200 < p < 500 μm and p > 500 μm) and seven concentrations of GTR (0%, 5%, 10%, 20%, 40%, 50% and 70%), resulting in a total of 21 new compounds. In addition, in order to have the dielectric tests as much exhaustive as possible and to show the behavior of the compound under widely changing conditions, a wide range of temperatures (30–120°C) and frequencies (1 × 10−2 Hz to 3 × 106 Hz) were taken into consideration. All these data have provided an accurate characterization of the properties of the new compounds, and according to these results, possible electrical applications have been explored, with the requirement that they must comply with official regulations.
Physical and mechanical characterization of self-reinforced wood–polymer composite produced by solid-state extrusion
Authors: Cai Jianchen , Jia Mingyin , Xue Ping , Ding Yun , Jin Xiaoming 
Published: February 2013

In this study, highly oriented self-reinforced wood–polymer composite (WPC) rods were produced by stable and continuous solid-state extrusion through a conical die. Polypropylene, softwood flour and inorganic filler were used at 50%, 40% and 10% weight concentration, respectively. The properties and morphology of the samples were studied by differential scanning calorimetry analyses, scanning electron microscopy observation and mechanics performance testing. Compared to a conventional extruded rod, the self-reinforced WPC rod profile exhibited a fibrillar structure largely parallel to the direction of extrusion, which contributed to the significantly high strength and modulus of the product as well as improved thermal properties and good dimensional stability. With the increase in draw ratio, the melting peak moved to high temperature, modulus (from 2200 to 5800 MPa) and strength (from 20.7 to 81.6 MPa) were greatly increased.
Genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis
Authors: Mylona Athina , Andrieu-Soler Charlotte , Thongjuea Supat , Martella Andrea , Soler Eric , Jorna Ruud , Hou Jun , Kockx Christel , van Ijcken Wilfred , Lenhard Boris , Grosveld Frank 
Published: February 2013

Key PointsLack of yolk-sac hematopoiesis in the Ldb1−/− mouse results from a decreased number of hemangioblasts and a differentiation block. Identification of genes and pathways regulated by Ldb1 in the hemangioblast reveals potential targets for early developmental manipulation.
M-pick, a modularity-based method for OTU picking of 16S rRNA sequences
Authors: Wang Xiaoyu , Yao Jin , Sun Yijun , Mai Volker 
Published: February 2013

Abstract

Background
Binning 16S rRNA sequences into operational taxonomic units (OTUs) is an initial crucial step in analyzing large sequence datasets generated to determine microbial community compositions in various environments including that of the human gut. Various methods have been developed, but most suffer from either inaccuracies or from being unable to handle millions of sequences generated in current studies. Furthermore, existing binning methods usually require a priori decisions regarding binning parameters such as a distance level for defining an OTU.

Results
We present a novel modularity-based approach (M-pick) to address the aforementioned problems. The new method utilizes ideas from community detection in graphs, where sequences are viewed as vertices on a weighted graph, each pair of sequences is connected by an imaginary edge, and the similarity of a pair of sequences represents the weight of the edge. M-pick first generates a graph based on pairwise sequence distances and then applies a modularity-based community detection technique on the graph to generate OTUs to capture the community structures in sequence data. To compare the performance of M-pick with that of existing methods, specifically CROP and ESPRIT-Tree, sequence data from different hypervariable regions of 16S rRNA were used and binning results were compared.

Conclusions
A new modularity-based clustering method for OTU picking of 16S rRNA sequences is developed in this study. The algorithm does not require a predetermined cut-off level, and our simulation studies suggest that it is superior to existing methods that require specified distance levels to define OTUs. The source code is available at http://plaza.ufl.edu/xywang/Mpick.htm.
Prediction of vitamin interacting residues in a vitamin binding protein using evolutionary information
Authors: Panwar Bharat , Gupta Sudheer , Raghava Gajendra P S 
Published: February 2013

Abstract

Background
The vitamins are important cofactors in various enzymatic-reactions. In past, many inhibitors have been designed against vitamin binding pockets in order to inhibit vitamin-protein interactions. Thus, it is important to identify vitamin interacting residues in a protein. It is possible to detect vitamin-binding pockets on a protein, if its tertiary structure is known. Unfortunately tertiary structures of limited proteins are available. Therefore, it is important to develop in-silico models for predicting vitamin interacting residues in protein from its primary structure.

Results
In this study, first we compared protein-interacting residues of vitamins with other ligands using Two Sample Logo (TSL). It was observed that ATP, GTP, NAD, FAD and mannose preferred {G,R,K,S,H}, {G,K,T,S,D,N}, {T,G,Y}, {G,Y,W} and {Y,D,W,N,E} residues respectively, whereas vitamins preferred {Y,F,S,W,T,G,H} residues for the interaction with proteins. Furthermore, compositional information of preferred and non-preferred residues along with patterns-specificity was also observed within different vitamin-classes. Vitamins A, B and B6 preferred {F,I,W,Y,L,V}, {S,Y,G,T,H,W,N,E} and {S,T,G,H,Y,N} interacting residues respectively. It suggested that protein-binding patterns of vitamins are different from other ligands, and motivated us to develop separate predictor for vitamins and their sub-classes. The four different prediction modules, (i) vitamin interacting residues (VIRs), (ii) vitamin-A interacting residues (VAIRs), (iii) vitamin-B interacting residues (VBIRs) and (iv) pyridoxal-5-phosphate (vitamin B6) interacting residues (PLPIRs) have been developed. We applied various classifiers of SVM, BayesNet, NaiveBayes, ComplementNaiveBayes, NaiveBayesMultinomial, RandomForest and IBk etc., as machine learning techniques, using binary and Position-Specific Scoring Matrix (PSSM) features of protein sequences. Finally, we selected best performing SVM modules and obtained highest MCC of 0.53, 0.48, 0.61, 0.81 for VIRs, VAIRs, VBIRs, PLPIRs respectively, using PSSM-based evolutionary information. All the modules developed in this study have been trained and tested on non-redundant datasets and evaluated using five-fold cross-validation technique. The performances were also evaluated on the balanced and different independent datasets.

Conclusions
This study demonstrates that it is possible to predict VIRs, VAIRs, VBIRs and PLPIRs from evolutionary information of protein sequence. In order to provide service to the scientific community, we have developed web-server and standalone software VitaPred (http://crdd.osdd.net/raghava/vitapred/).