bluuebunny/crossref_metadata_2025_split huggingface dataset:
Future prospects in immunosuppression for liver transplantation
Authors: Fung John J. , Bollinger Jessica E. , Miller Charles , Eghtesad Bijan 
Published: August 2011

Key Points
1. Our increasing understanding of signaling pathways and cellular interactions in transplant immunobiology and the availability of novel immunosuppressive agents have facilitated targeted strategies.
2. The driving forces behind the development of new immunosuppressive regimens are the long-term complications of current immunosuppressive regimens (particularly renal dysfunction and metabolic disturbances).
3. By regulatory mandate, the requirement for the primary endpoint to be a composite of death, graft loss, and rejection remains intact; however, current and future clinical trials could incorporate key secondary endpoints that address renal and metabolic derangements.
Hot-topic debate on hepatitis C virus: The type of immunosuppression matters
Authors: Trotter James F. 
Published: August 2011

Key Points
1. The treatment of rejection is an important factor associated with the severe recurrence of hepatitis C virus (HCV) after liver transplantation.
2. The effects of calcineurin inhibitors, corticosteroids, and mycophenolate mofetil on HCV recurrence are equivocal.
3. Cyclosporine is associated with a higher sustained virological response in patients treated for HCV.
4. Because insulin resistance and diabetes are associated with fibrosis in HCV-infected liver transplant recipients, the use of immunosuppressive agents without this side effect may slow the posttransplant disease progression.
Carbon Monoxide Induces Hypothermia Tolerance in Kupffer Cells and Attenuates Liver Ischemia/Reperfusion Injury in Rats†
Authors: Lee Lung-Yi , Kaizu Takashi , Toyokawa Hideyoshi , Zhang Matthew , Ross Mark , Stolz Donna B. , Huang Chao , Gandhi Chandrashekhar , Geller David A. , Murase Noriko 
Published: August 2011

Abstract
Ischemia/reperfusion (I/R) injury in liver grafts, which is initiated by cold preservation and is augmented by reperfusion, is a major problem that complicates graft quality, posttransplant patient care, and outcomes of liver transplantation (LT). Kupffer cells (KCs) play important roles in I/R injury; however, little is known about their changes during cold preservation. We examined whether a pretreatment with carbon monoxide (CO), a cytoprotective product of heme degradation, could influence KC activity during cold storage and protect liver grafts against LT-induced I/R injury. In vitro, primary rat KCs were stimulated for 24 hours under hypothermic conditions (4°C, 20% O2), with lipopolysaccharide, or under hypoxic conditions (37°C, 5% O2) with or without a CO pretreatment. When rat KCs were exposed to hypothermic conditions, they produced reactive oxygen species (ROS), but they did not produce tumor necrosis factor α (TNF-α) or nitric oxide. The preincubation of KCs with CO up-regulated heat shock protein 70 (HSP70) and inhibited ROS generation. When liver grafts from donor rats exposed to CO (250 ppm) for 24 hours were transplanted after 18 hours of cold preservation in University of Wisconsin solution, HSP70 expression increased in these grafts versus control grafts, and serum aspartate aminotransferase and alanine aminotransferase levels as well as necrotic areas and inflammatory infiltrates were significantly reduced after LT. CO-pretreated liver grafts showed less up-regulation of TNF-α and inducible nitric oxide synthase messenger RNA (mRNA) and reduced expression of proapoptotic B cell lymphoma 2–associated X protein mRNA, cleaved caspase-3, and poly(adenosine diphosphate ribose) polymerase. In conclusion, the pretreatment of donors with CO ameliorates LT-associated I/R injury with increased hepatic HSP70 expression, particularly in the KC population. Liver Transpl, 2011. © 2011 AASLD.
A Randomized, Multicenter Study Comparing Steroid-Free Immunosuppression and Standard Immunosuppression for Liver Transplant Recipients With Chronic Hepatitis C†
Authors: Klintmalm Göran B. , Davis Gary L. , Teperman Lewis , Netto George J. , Washburn Kenneth , Rudich Stephen M. , Pomfret Elizabeth A. , Vargas Hugo E. , Brown Robert , Eckhoff Devin , Pruett Timothy L. , Roberts John , Mulligan David C. , Charlton Michael R. , Heffron Thomas G. , Ham John M. , Douglas David D. , Sher Linda , Baliga Prabhakar K. , Kinkhabwala Milan , Koneru Baburao , Abecassis Michael , Millis Michael , Jennings Linda W. , Fasola Carlos G. 
Published: August 2011

Abstract
This randomized, prospective, multicenter trial compared the safety and efficacy of steroid-free immunosuppression (IS) to the safety and efficacy of 2 standard IS regimens in patients undergoing transplantation for hepatitis C virus (HCV) infection. The outcome measures were acute cellular rejection (ACR), severe HCV recurrence, and survival. The patients were randomized (1:1:2) to tacrolimus (TAC) and corticosteroids (arm 1; n = 77), mycophenolate mofetil (MMF), TAC, and corticosteroids (arm 2; n = 72), or MMF, TAC, and daclizumab induction with no corticosteroids (arm 3; n = 146). In all, 295 HCV RNA–positive subjects were enrolled. At 2 years, there were no differences in ACR, HCV recurrence (biochemical evidence), patient survival, or graft survival rates. The side effects of IS did not differ, although there was a trend toward less diabetes in the steroid-free group. Liver biopsy samples revealed no significant differences in the proportions of patients in arms 1, 2, and 3 with advanced HCV recurrence (ie, an inflammation grade ≥ 3 and/or a fibrosis stage ≥ 2) in years 1 (48.2%, 50.4%, and 43.0%, respectively) and 2 (69.5%, 75.9%, and 68.1%, respectively). Although we have found that steroid-free IS is safe and effective for liver transplant recipients with chronic HCV, steroid sparing has no clear advantage in comparison with traditional IS. Liver Transpl, 2011. © 2011 AASLD.
Computed Tomography Liver Volumetry Using 3-Dimensional Image Data in Living Donor Liver Transplantation: Effects of the Slice Thickness on the Volume Calculation†
Authors: Hori Masatoshi , Suzuki Kenji , Epstein Mark L. , Baron Richard L. 
Published: August 2011

Abstract
The purpose of this study was to evaluate the relationship between the slice thickness and the calculated volume in computed tomography (CT) liver volumetry through the comparison of the results from images [including 3-dimensional (3D) images] with various slice thicknesses. Twenty potential adult liver donors (12 men and 8 women) with a mean age of 39 years (range = 24-64 years) underwent CT with a 64-section multidetector row CT scanner after the intravenous injection of a contrast material. Four image sets with slice thicknesses of 0.625, 2.5, 5, and 10 mm were used. First, a program developed in our laboratory for automated liver extraction was applied to the CT images, and the liver boundaries were determined automatically. Then, an abdominal radiologist reviewed all images onto which automatically extracted boundaries had been superimposed and then edited the boundaries on each slice to enhance the accuracy. The liver volumes were determined via the counting of the voxels within the liver boundaries. The mean whole liver volumes estimated with CT were 1322.5 cm3 from 0.625-mm images, 1313.3 cm3 from 2.5-mm images, 1310.3 cm3 from 5-mm images, and 1268.2 cm3 from 10-mm images. The volumes calculated from 3D (0.625-mm) images were significantly larger than the volumes calculated from thicker images (P < 0.001). The partial liver volumes of right lobes, left lobes, and lateral segments were evaluated in a similar manner. The estimated maximum difference in the calculated volumes of lateral segments was −10.9 cm3 (−4.63%) between 0.625- and 5-mm images. In conclusion, liver volumes calculated from 2.5-mm-thick or thicker images are significantly smaller than liver volumes calculated from 3D images. If a maximum error of 5% in the calculated graft volume will not have a significant clinical impact, 5-mm-thick images are acceptable for CT volumetry. If the impact is significant, 3D images could be essential. Liver Transpl, 2011. © 2011 AASLD.
Hot-topic debate on tolerance: Immunosuppression withdrawal
Authors: Sánchez-Fueyo Alberto 
Published: August 2011

Key Points
1. Liver allografts exhibit intrinsic tolerogenic properties that result in their spontaneous acceptance in many experimental animal models.
2. In clinical transplantation, liver allografts require milder immunosuppression regimens than other organs, are relatively resistant to antibody-mediated rejection, and only very rarely are lost because of immunological insults.
3. A fraction of stable liver transplant recipients can withdraw from all immunosuppression therapy and then maintain normal graft function and not experience rejection. This phenomenon is known as spontaneous operational tolerance (SOT).
4. The intentional discontinuation of immunosuppression in stable liver transplant recipients has led to successful weaning in almost 20% of recipients, but the true prevalence of SOT in unselected recipients is still unknown.
5. The prevalence could be higher in pediatric recipients undergoing transplantation before 1 year of age and in adult recipients with more than 10 years of posttransplant follow-up.
6. Rejection occurring during medically supervised immunosuppression weaning trials tends to be mild and, in the overwhelming majority of cases, can be easily resolved without the administration of high-dose immunosuppression.
7. Tolerant liver recipients exhibit specific transcriptional patterns in peripheral blood and liver tissue that may constitute future diagnostic markers of tolerance.
8. There is still no formal proof that the discontinuation of low-dose immunosuppression in long-term survivors of liver transplantation improves the morbidity and mortality rates associated with immunosuppression therapy.
Immunosuppression in pediatric liver transplantation: Are little people different?
Authors: Dhawan Anil 
Published: August 2011

Key Points
1. Children differ from adults in the pharmacokinetics and dynamics of most immunosuppressive agents.
2. A lack of clinical trials continues to be an issue for newer agents.
3. On the basis of clinical case series, mycophenolate mofetil and sirolimus are increasingly being used as renal-sparing agents.
4. In comparison with adults, the recurrence of both viral hepatitis and hepatocellular carcinoma is less of an issue in children.
5. Particular attention should be paid to complete age-appropriate immunization to avoid vaccine-preventable diseases.
6. Paying special attention to adherence and the transition to adult services is essential for minimizing graft loss.
Modeling Choices for Virtual Screening Hit Identification
Authors: Bergeron Charles , Krein Michael , Moore Gregory , Breneman Curt M. , Bennett Kristin P. 
Published: August 2011

AbstractMaking suitable modeling choices is crucial for successful in silico drug design, and one of the most important of these is the proper extraction and curation of data from qHTS screens, and the use of optimized statistical learning methods to obtain valid models. More specifically, we aim to learn the top‐1 % most potent compounds against a variety of targets in a procedure we call virtual screening hit identification (VISHID). To do so, we exploit quantitative high‐throughput screens (qHTS) obtained from PubChem, descriptors derived from molecular structures, and support vector machines (SVM) for model generation. Our results illustrate how an appreciation of subtle issues underlying qHTS data extraction and the resulting SVM models created using these data can enhance the effectiveness of solutions and, in doing so, accelerate drug discovery.
A Survey of Evidence‐Based Practise among Dutch Occupational Therapists
Authors: Döpp Carola M. E. , Steultjens Esther M. J. , Radel Jeff 
Published: August 2011

AbstractThis study explored how the evidenced‐based practise (EBP) is perceived by Dutch occupational therapists (OTs), what sources of research data are used to make clinical decisions, and what barriers are identified in implementing EBP.A self‐administered, pre‐tested, questionnaire was distributed through an email survey and postal mail among the 200 randomly stratified selected OTs out of a total population of 2,019 Dutch OTs. Analyses of data comprised descriptive statistics of all variables and test statistics to evaluate the differences between demographical groups.Dutch OTs have a very positive attitude toward the EBP. Barriers experienced are mostly related to a lack of skills needed to implement the EBP and to the characteristics of the work environment. The attitude, experiences and barriers are mainly similar to research findings in other countries or professions. A unique barrier to the implementation of the EBP found in this study was that Dutch OTs perceived evidence written in a foreign (non‐Dutch) language as a barrier to using evidence in non‐Dutch languages.The results of the study, derived from a partly representative group of working OTs, implicate universal problems regarding the effective implementation of the EBP. Solutions to increase the implementation of the EBP from an international point of view are called for and need to be evaluated. Copyright © 2011 John Wiley & Sons, Ltd.
Tissue doppler evaluation of systolic and diastolic cardiac functions in long‐term survivors of Hodgkin lymphoma
Authors: Alehan Dursun , Şahin Murat , Varan Ali , Yıldırım Işıl , Küpeli Serhan , Büyükpamukçu Münevver 
Published: August 2011

AbstractBackgroundMonitoring for late adverse events is crucial in long‐term management of childhood cancer survivors. A case–control study to evaluate long‐term cardiovascular status of childhood Hodgkin lymphoma (HL) using tissue Doppler imaging (TDI) was performed.Patients and MethodsPatients diagnosed with HL before age of 18 that completed therapy and were in remission and a control group of healthy children were evaluated by echocardiography and TDI.ResultsTotal of 72 HL survivors were included in the study. Median age at diagnosis, remission time, and age at time of echocardiography were 7 (2–16), 9 (2–20), and 17.5 (7–27) years, respectively. TDI revealed decreased S′ velocity, reflecting systolic dysfunction in HL survivors, at medial and lateral mitral annuli and at middle segment of interventricular septum (IVS; P < 0.01) for all. Moreover, TDI showed decreased peak E′ velocity at medial mitral annulus [12.4 cm/s (5.5–16.3) vs. 13.3 cm/s (10.2–18.9), P = 0.03] and at middle segment of IVS [10 cm/s (5.3–16.3) vs. 11.6 cm/s (6.7–16.7), P < 0.01] and prolongation of isovolemic relaxation time at medial and lateral annuli of the mitral valve (P < 0.01) and at middle segment of IVS (P = 0.03) suggesting diastolic dysfunction in HL survivors.ConclusionCardiac dysfunction after childhood cancer therapy may develop after many years. Since systolic and diastolic dysfunction can be seen in these patients periodic echocardiographic screening of both systolic and diastolic function in the survivors of HL might be useful in the follow‐up of these patients. Pediatr Blood Cancer 2012; 58: 250–255. © 2011 Wiley Periodicals, Inc.
Preclinical evaluation of pemetrexed in pediatric solid tumors
Authors: Norris Robin E. , Rappaport Eric F. , Adamson Peter C. 
Published: August 2011

AbstractRenewed interest in antifols for the treatment of childhood cancers has resulted from identification of novel antifols with broad spectrums of anti‐cancer activity. We evaluated the in vitro cytotoxicity of methotrexate and pemetrexed in a panel of 12 pediatric solid tumor cell lines using the sulforhodamine‐B assay. The Ewing sarcoma (ES) cell lines demonstrated the greatest sensitivity to both methotrexate and pemetrexed. Expression of folate pathway genes (DHFR, TS, GARFT, GGH) did not correlate with in vitro drug sensitivity. Further evaluation of pemetrexed for the treatment of ES is warranted. Pediatr Blood Cancer 2011; 57: 1233–1235. © 2011 Wiley Periodicals, Inc.
Major bleeding risk associated with warfarin and co‐medications in the elderly population
Authors: Vitry Agnes I. , Roughead Elizabeth E. , Ramsay Emmae N. , Preiss Adrian K. , Ryan Philip , Gilbert Andrew L. , Caughey Gillian E. , Shakib Sepehr , Esterman Adrian , Zhang Ying , McDermott Robyn A 
Published: August 2011

ABSTRACTPurposeWarfarin management in the elderly population is complex as medicines prescribed for concomitant diseases may further increase the risk of major bleeding associated with warfarin use. We aimed to quantify the excess risk of bleeding‐related hospitalisation when warfarin was co‐dispensed with potentially interacting medicines.MethodsA retrospective cohort study was undertaken over a 4‐year period from July 2002 to June 2006 to examine bleeding risk associated with medications co‐administered in patients taking warfarin using an administrative claims database from the Australian Department of Veterans' Affairs. All veterans aged 65 years and over who were new users of warfarin were followed until death or study end. Risk of bleeding was assessed using a Poisson GEE model adjusting for age, gender, socioeconomic status, co‐morbidity index, previous bleeding related hospitalisations and indicators of health service use.ResultsOverall, 17661 veterans who used warfarin at any time during the study period were included. The overall incidence rate of bleeding‐related hospitalisations was 4.1 (95% CI 3.7–4.6) per 100 person‐years in veterans who were not receiving potentially interacting medicines. Bleeding‐related hospitalisation rates were significantly increased when warfarin was co‐prescribed with low‐dose aspirin (Adjusted rate ratio (AdjRR) 1.44, 95% CI 1.00–2.07), clopidogrel (AdjRR 2.23, 95% CI 1.48–3.36), clopidogrel with aspirin (AdjRR 3.44, 95% CI 1.28–9.23), amiodarone (AdjRR 3.33, 95% CI 1.38–8.00) and antibiotics (AdjRR 2.34, 95% CI 1.55–3.54).ConclusionsModels assessing bleeding risk with warfarin should take account of the range of potentially harmful medicine combinations used in elderly people with comorbid conditions. Copyright © 2011 John Wiley & Sons, Ltd.
Functionalization of graphene oxide towards thermo‐sensitive nanocomposites via moderate in situ SET‐LRP
Authors: Deng Yan , Li Yongjun , Dai Jing , Lang Meidong , Huang Xiaoyu 
Published: August 2011

AbstractA mild and efficient strategy is presented for growing thermo‐sensitive polymers directly from the surface of exfoliated graphene oxide (GO). This method involves the covalent attachment of Br‐containing initiating groups onto the surface of GO sheets followed by in situ growing poly[poly(ethylene glycol) ethyl ether methacrylate] (PPEGEEMA) via single‐electron‐transfer living radical polymerization (SET‐LRP). Considering the lack of reactive functional groups on the surface of GO, exfoliated GO sheets were subjected to an epoxide ring opening reaction with tris(hydroxymethyl) aminomethane (TRIS) at room temperature. The initiating groups were grafted onto TRIS‐GO sheets by treating hydroxyls with 2‐bromo‐2‐methylpropionyl bromide at room temperature. PPEGEEMA chains were synthesized by in situ SET‐LRP using CuBr/Me6TREN as catalytic system at 40 °C in H2O/THF. The resulting materials were characterized using a range of testing techniques and it was proved that polymer chains were successfully introduced to the surface of GO sheets. After grafting with PPEGEEMA, the modified GO sheets still maintained the separated single layers and the dispersibility was significantly improved. This TRIS‐GO‐PPEGEEMA hybrid material shows reversible self‐assembly and deassembly in water by switching temperature at about 34 °C. Such smart graphene‐based materials promise important potential applications in thermally responsive nanodevices and microfluidic switches. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Three different β‐cyclodextrins direct the emulsion copolymerization of a highly fluorinated methacrylate toward distinctive nanostructured particle morphologies
Authors: Yang Chengcheng , Castelvetro Valter , Scalarone Dominique , Bianchi Sabrina , Zhang Yongming 
Published: August 2011

AbstractStable colloidal dispersions of nanostructured semifluorinated acrylic particles with an unfluorinated core and an outer layer consisting of copolymers of the highly hydrophobic and lipophobic heptadecafluorodecyl methacrylate (FMA) were successfully synthesized with the assistance of three different cyclodextrins as phase‐transfer catalysts: β‐cyclodextrin (β‐CD), hydroxypropyl β‐cyclodextrin (HpCD), and methyl β‐cyclodextrin (MeCD). While all the cyclodextrins form a stable inclusion complex (IC) with FMA, only the ICs with the more hydrophilic HpCD and MeCD are soluble in water. Nevertheless, incorporation of FMA in the particle shell copolymer could be achieved also when using β‐CD. On the other hand, the morphology of the nanostructured particles was characterized by a “patchy” fluorinated shell dependent on the cyclodextrin used, the best results being obtained with MeCD. A monomer‐starved semicontinuous emulsion polymerization procedure was essential to favor the CD‐mediated incorporation of FMA into the copolymer structure and to achieve a stable colloidal dispersion even in the presence of small amounts of mixed anionic–nonionic surfactants. The thermal and surface properties of the latex films showed a good correlation with the shell composition and patchy nanostructured morphology of the particles. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
SET‐LRP of methyl acrylate catalyzed with activated Cu(0) wire in methanol in the presence of air
Authors: Nguyen Nga H. , Percec Virgil 
Published: August 2011

AbstractSingle electron transfer‐living radical polymerization (SET‐LRP) of methyl acrylate (MA) in methanol, catalyzed with nonactivated and activated Cu(0) wires, was performed in the presence of nondeoxygenated reagents and was investigated under a simple blanket of nitrogen. The addition of a small amount of hydrazine hydrate mediates the deoxygenation of the reaction mixture by the consumption of oxygen through its use to oxidize Cu(0) to Cu2O, followed by the reduction of Cu2O with hydrazine back to the active Cu(0) catalyst. SET‐LRP of MA in methanol in the presence of air requires a smaller dimension of Cu(0) wire, compared to the nonactivated Cu(0) wire counterpart. Activation of Cu(0) wire allowed the polymerization in air to proceed with no induction period, linear first‐order kinetics, linear correlation between the molecular weight evolution with conversion, and narrow molecular weight distribution. The retention of chain‐end functionality of α,ω‐di(bromo) poly(methyl acrylate) (PMA) prepared by SET‐LRP was demonstrated by a combination of experiments including 1H NMR spectroscopy and matrix‐assisted laser desorption ionization–time of flight mass spectrometry after thioetherification of α,ω‐di(bromo) PMA with thiophenol. In SET‐LRP of MA in the presence of limited air, bimolecular termination is observed only above 85% conversion. However, for bifunctional initiators, the small amount of bimolecular termination observed at high conversion maintains a perfectly bifunctional polymer. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011