bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of transmission associated with sharing drug injecting paraphernalia: analysis of recent hepatitis C virus (HCV) infection using cross‐sectional survey data
Authors: Palmateer N. , Hutchinson S. , McAllister G. , Munro A. , Cameron S. , Goldberg D. , Taylor A. 
Published: May 2013

SummarySharing injecting paraphernalia (containers, filters and water) poses a risk of transmitting the hepatitis C virus (HCV). The prevalence of, and risk of HCV from, such behaviour has not been extensively reported in Europe. People who inject drugs (PWID) were recruited in cross‐sectional surveys from services providing sterile injecting equipment across Scotland between 2008 and 2010. Participants completed a questionnaire and provided a blood spot for anonymous testing. Logistic regression was used to examine the association between recent HCV infection (anti‐HCV negative and HCV‐RNA positive) and self‐reported measures of injecting equipment sharing in the 6 months preceding interview. Twelve per cent of the sample reported sharing needles/syringes, and 40% reported sharing paraphernalia in the previous 6 months. The adjusted odds ratios (AOR) for sharing needles/syringes (+/− paraphernalia), and sharing only paraphernalia in the last 6 months were 6.7 (95% CI 2.6–17.1) and 3.0 (95% CI 1.2–7.5), respectively. Among those who reported not sharing needles/syringes, sharing containers and filters were both significantly associated with recent HCV infection (AOR 3.1, 95% CI 1.3–7.8 and 3.1, 95% CI 1.3–7.5, respectively); sharing water was not. We present the first study to apply a cross‐sectional approach to the analysis of the association between sharing paraphernalia and incident HCV infection and demonstrate consistent results with previous longitudinal studies. The prevalence of paraphernalia sharing in our study population is high, representing significant potential for HCV transmission.
Dosing regimen and tolerability of methoxy polyethylene glycol–epoetin beta in Chinese dialysis patients
Authors: Choy Bo Ying , Lam Man Fai , Yip Terence , Tang Hon Lok , Wong Ping Nam , Chow Chik Cheung Vincent , Yap Desmond YH , Chan Tak Mao 
Published: May 2013

Abstract:AimTo investigate methoxy polyethylene glycol‐epoetin beta dosing regimen in treatment naïve subjects and dose conversion in darbepoetin alpha treated subjects, in Chinese dialysis patients.MethodsAdult Chinese patients on peritoneal dialysis (PD) or haemodialysis (HD), with no prior treatment with erythropoiesis‐stimulating agents and haemoglobin below 8 g/dL (Group I) or receiving darbepoetin alpha and had stable haemoglobin at 10–12 g/dL (Group II) were included in this prospective open‐label study. In Group I methoxy polyethylene glycol‐epoetin beta was started at 0.6 μg/kg subcutaneously fortnightly till haemoglobin reached 10 g/dL, after which it was given monthly. A dose conversion table was devised for Group II. Follow‐up was 36 weeks.ResultsForty‐five patients were included. Haemoglobin in Group I (n = 23, PD/HD:19/4) increased from 7.5 ± 0.9 g/dL at baseline to 10.7 ± 1.0 g/dL after 16 weeks, while it remained stable at 10.4 ± 1.0 g/dL after conversion in Group II (n = 22, PD/HD:15/7). Actual dose required after stabilization was 1.7 μg/kg per month in Group I and 2.3 μg/kg per month in Group II. Median number of dose adjustment was three in Group I and one in Group II, while haemoglobin overshoot to 13 g/dL or above occurred in 4.4% and 9.1%, respectively. No significant side‐effect was observed.ConclusionsOur dosing regimen for methoxy polyethylene glycol‐epoetin beta, for treatment naïve subjects or for conversion from darbepoetin alpha, is safe and effective. The dose required to achieve a haemoglobin concentration of 10–11 g/dL in Chinese dialysis patients is approximately 2 μg/kg monthly.
Predictors of cardiac allograft vasculopathy in pediatric heart transplant recipients
Authors: Kobayashi Daisuke , Du Wei , L'Ecuyer Thomas J. 
Published: May 2013

AbstractCAV remains a leading cause of late graft loss and mortality among survivors of pediatric heart transplantation. We sought to define the incidence of CAV and identify its predictors in pediatric heart transplant recipients. The OPTN/UNOS database was analyzed for pediatric recipients who underwent heart transplant between 1987 and 2011. The primary end‐point is time from heart transplantation to development of CAV (CAV‐free survival). To identify predictors of CAV‐free survival, demographic and transplant data were analyzed by the Kaplan–Meier survival method and Cox proportional hazards regression. Of 5211 pediatric heart transplant recipients with at least one‐yr follow‐up, the incidence of CAV at five, 10, and 15 yr was 13%, 25%, and 54%, respectively. Multivariate analysis found that risk of CAV was associated with the following variables: Recipient age 1–4 yr (HR 1.25), 5–9 yr (1.45), 10–18 yr (1.83), donor age >18 yr (1.34), re‐transplantation (2.14), recipient black race (1.55), and donor cigarette use (1.54). Older recipient and donor age, recipient black race, donor cigarette use, and re‐transplantation were highly associated with shorter CAV‐free survival.
Psychometric properties of The Hospital Anxiety and Depression Scale and The General Health Questionnaire‐20 in COPD inpatients
Authors: Bratås Ola , Grønning Kjersti , Forbord Toril 
Published: May 2013

Aim: To compare the psychometric properties between the Hospital Anxiety and Depression Scale (HADS) and General Health Questionnaire–version 20 (GHQ‐20) in detecting psychological distress in COPD patients referred to pulmonary rehabilitation, and to examine the factor structure of GHQ‐20. Methods: The study comprised 161 consecutive patients with mild to very severe COPD. For comparison of mean scores between the HADS and GHQ‐20, one sample t‐test was used. Potential differences in the detection of possible and normal cases were analysed using Pearson Chi square test. We report Pearson's correlations within and between the questionnaires, and internal consistency was assessed through Chronbach's alpha. The factor structure of the GHQ‐20 was examined through principal axis factoring (PAF) with oblique rotation and eigenvalue >1. Results: There were no differences in mean scores of psychological distress between HADS and GHQ‐20 (12.03 vs. 24.73, p = 0.000), as well as no differences in the prevalence of possible cases of psychological distress (34.6 vs. 36.9, p = 0.000) and normal cases (65.4 vs. 63.1, p = 0.000). The observed difference between HADS and GHQ‐20 regarding internal consistency was marginal, with Chronbach's alpha coefficients of 0.91 and 0.94, respectively. The PAF analysis resulted in a three‐factor solution for GHQ‐20, notably with only two items loading on the third factor, giving an internal consistency <0.70. A two‐factor solution, comprising anxiety/depression and coping, may therefore be more appropriate. Conclusions: This study demonstrates no significant differences between the HADS and GHQ‐20 in their ability to detect possible cases of psychological distress in a rehabilitation setting for COPD patients. Although the HADS and GHQ‐20 are measuring different concepts of psychological distress, both questionnaires can be recommended as screening tools for detection of psychological distress in COPD inpatients. The GHQ‐20 appears to be two‐dimensional, comprising anxiety/depression as one dimension, and coping as the other dimension.
Coverage‐adjusted Confidence Intervals for a Binomial Proportion
Authors: Thulin Måns 
Published: May 2013

ABSTRACTWe consider the classic problem of interval estimation of a proportion p based on binomial sampling. The ‘exact’ Clopper–Pearson confidence interval for p is known to be unnecessarily conservative. We propose coverage adjustments of the Clopper–Pearson interval that incorporate prior or posterior beliefs into the interval. Using heatmap‐type plots for comparing confidence intervals, we show that the coverage‐adjusted intervals have satisfying coverage and shorter expected lengths than competing intervals found in the literature.
Bulky “Gatekeeper” Residue Changes the Cosubstrate Specificity of Aminoglycoside 2″-Phosphotransferase IIa
Authors: Bhattacharya Monolekha , Toth Marta , Smith Clyde A. , Vakulenko Sergei B. 
Published: May 2013

ABSTRACT

The aminoglycoside 2″-phosphotransferases APH(2″)-IIa and APH(2″)-IVa can utilize ATP and GTP as cosubstrates, since both enzymes possess overlapping but discrete structural templates for ATP and GTP binding. APH(2″)-IIIa uses GTP exclusively, because its ATP-binding template is blocked by a bulky tyrosine “gatekeeper” residue. Replacement of the “gatekeeper” residues M85 and F95 in APH(2″)-IIa and APH(2″)-IVa, respectively, by tyrosine does not significantly change the antibiotic susceptibility profiles produced by the enzymes. In APH(2″)-IIa, M85Y substitution results in an ∼10-fold decrease in the

K
m

value of GTP and an ∼320-fold increase in the

K
m

value of ATP. In APH(2″)-IVa, F95Y substitution results in a modest decrease in the

K
m

values of both GTP and ATP. Structural analysis indicates that in the APH(2″)-IIa M85Y mutant, tyrosine blocks access of ATP to the correct position in the binding site, while the larger nucleoside triphosphate (NTP)-binding pocket of the APH(2″)-IVa F95Y mutant allows the tyrosine to move away, thus giving access to the ATP-binding template.
Two Human Host Defense Ribonucleases against Mycobacteria, the Eosinophil Cationic Protein (RNase 3) and RNase 7
Authors: Pulido David , Torrent Marc , Andreu David , Nogués M. Victoria , Boix Ester 
Published: May 2013

ABSTRACT

There is an urgent need to develop new agents against mycobacterial infections, such as tuberculosis and other respiratory tract or skin affections. In this study, we have tested two human antimicrobial RNases against mycobacteria. RNase 3, also called the eosinophil cationic protein, and RNase 7 are two small cationic proteins secreted by innate cells during host defense. Both proteins are induced upon infection displaying a wide range of antipathogen activities. In particular, they are released by leukocytes and epithelial cells, contributing to tissue protection. Here, the two RNases have been proven effective against
Mycobacterium vaccae
at a low micromolar level. High bactericidal activity correlated with their bacterial membrane depolarization and permeabilization activities. Further analysis on both protein-derived peptides identified for RNase 3 an N-terminus fragment that is even more active than the parental protein. Also, a potent bacterial agglutinating activity was unique to RNase 3 and its derived peptide. The particular biophysical properties of the RNase 3 active peptide are envisaged as a suitable reference for the development of novel antimycobacterial drugs. The results support the contribution of secreted RNases to the host immune response against mycobacteria.
In VitroandIn VivoActivities of Dicationic Diguanidino Compounds against Echinococcus multilocularis Metacestodes
Authors: Küster Tatiana , Kriegel Nadja , Boykin David W. , Stephens Chad E. , Hemphill Andrew 
Published: May 2013

ABSTRACTAlveolar echinococcosis (AE) is a disease predominantly affecting the liver, with metacestodes (larvae) of the tapewormEchinococcus multilocularisproliferating and exhibiting tumor-like infiltrative growth. For many years, chemotherapeutical treatment against alveolar echinococcosis has relied on the benzimidazoles albendazole and mebendazole, which require long treatment durations and exhibit parasitostatic rather than parasiticidal efficacy. Although benzimidazoles have been and still are beneficial for the patients, there is clearly a demand for alternative and more efficient treatment options. Aromatic dications, more precisely a small panel of di-N-aryl-diguanidino compounds, were screened for efficacy againstE. multilocularismetacestodesin vitro. Only those with a thiophene core group were active against metacestodes, while furans were not. The most active compound, DB1127, was further investigated in terms ofin vivoefficacy in mice experimentally infected withE. multilocularismetacestodes. This diguanidino compound was effective against AE when administered intraperitoneally but not when applied orally. Thus, thiophene-diguanidino derivatives with improved bioavailability when administered orally could lead to treatment options against AE.
Development of a Chimeric Plasmodium berghei Strain Expressing the Repeat Region of the P. vivax Circumsporozoite Protein forIn VivoEvaluation of Vaccine Efficacy
Authors: Espinosa Diego A. , Yadava Anjali , Angov Evelina , Maurizio Paul L. , Ockenhouse Christian F. , Zavala Fidel 
Published: May 2013

ABSTRACTThe development of vaccine candidates againstPlasmodium vivax—the most geographically widespread human malaria species—is challenged by technical difficulties, such as the lack ofin vitroculture systems and availability of animal models. Chimeric rodentPlasmodiumparasites are safe and useful tools for the preclinical evaluation of new vaccine formulations. We report the successful development and characterization of chimericPlasmodium bergheiparasites bearing the type I repeat region ofP. vivaxcircumsporozoite protein (CSP). TheP. berghei-P. vivaxchimeric strain develops normally in mosquitoes and produces highly infectious sporozoites that produce patent infection in mice that are exposed to the bites of as few as 3P. berghei-P. vivax-infected mosquitoes. Using this transgenic parasite, we demonstrate that monoclonal and polyclonal antibodies againstP. vivaxCSP strongly inhibit parasite infection and thus support the notion that these antibodies play an important role in protective immunity. The chimeric parasites we developed represent a robust model for evaluating protective immune responses againstP. vivaxvaccines based on CSP.
Preferred place of death for patients referred to a specialist palliative care service
Authors: Arnold Elizabeth , Finucane Anne M , Oxenham David 
Published: May 2013

ObjectivesUnderstanding patients’ preferences for place of death and supporting patients to achieve their wishes has become a priority. This study aims to: (1) examine preferences of patients referred to a specialist palliative care service; (2) determine whether preferences of those who have been admitted as hospice inpatients differ from those who have not; (3) identify reasons why preferred place of death (PPD) is sometimes not recorded; and (iv) investigate whether nominating a PPD relates to actual place of death.MethodPPD information was collected as part of standard care for all patients referred to a specialist palliative care service. Case notes were reviewed retrospectively for 1127 patients who died under the care of the service.ResultsSeventy-seven percent of the patients expressed a PPD, a further 21% of patients had documented reasons for PPD remaining unknown. Eighty percent of patients who had never been admitted to the hospice wanted to die at home. In contrast, 79% of those with at least one hospice inpatient admission wanted to die in the hospice. Patients who had an unknown PPD were three times more likely to die in hospital.ConclusionsMost patients in a specialist palliative care setting are willing to express a PPD. Preferences differ for patients who had never been admitted as hospice inpatients from those who have had at least one inpatient stay. Routine and ongoing assessment of PPD are recommended to support patients’ wishes at the end of life.
Phase II Study of Lutetium-177–Labeled Anti-Prostate-Specific Membrane Antigen Monoclonal Antibody J591 for Metastatic Castration-Resistant Prostate Cancer
Authors: Tagawa Scott T. , Milowsky Matthew I. , Morris Michael , Vallabhajosula Shankar , Christos Paul , Akhtar Naveed H. , Osborne Joseph , Goldsmith Stanley J. , Larson Steve , Taskar Neeta Pandit , Scher Howard I. , Bander Neil H. , Nanus David M. 
Published: May 2013

Abstract
Purpose: To assess the efficacy of a single infusion of radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (lutetium-177; 177Lu) by prostate-specific antigen (PSA) decline, measurable disease response, and survival.
Experimental Design: In this dual-center phase II study, two cohorts with progressive metastatic castration-resistant prostate cancer received one dose of 177Lu-J591 (15 patients at 65 mCi/m2, 17 at 70 mCi/m2) with radionuclide imaging. Expansion cohort (n = 15) received 70 mCi/m2 to verify response rate and examine biomarkers.
Results: Forty-seven patients who progressed after hormonal therapies (55.3% also received prior chemotherapy) received 177Lu-J591. A total of 10.6% experienced ≥50% decline in PSA, 36.2% experienced ≥30% decline, and 59.6% experienced any PSA decline following their single treatment. One of 12 with measurable disease experienced a partial radiographic response (8 with stable disease). Sites of prostate cancer metastases were targeted in 44 of 47 (93.6%) as determined by planar imaging. All experienced reversible hematologic toxicity, with grade 4 thrombocytopenia occurring in 46.8% (29.8% received platelet transfusions) without significant hemorrhage. A total of 25.5% experienced grade 4 neutropenia, with one episode of febrile neutropenia. The phase I maximum tolerated dose (70 mCi/m2) resulted in more 30% PSA declines (46.9% vs. 13.3%, P = 0.048) and longer survival (21.8 vs. 11.9 months, P = 0.03), but also more grade 4 hematologic toxicity and platelet transfusions. No serious nonhematologic toxicity occurred. Those with poor PSMA imaging were less likely to respond.
Conclusion: A single dose of 177Lu-J591 was well tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose response. Imaging biomarkers seem promising. Clin Cancer Res; 19(18); 5182–91. ©2013 AACR.
A Neu View of Invasive Lobular Breast Cancer
Authors: Bose Ron 
Published: May 2013

Abstract
Genome sequencing of relapsed, invasive lobular breast cancer identified actionable mutations in 86% of the cases. HER2 alterations occur in 27% of the cases, including 4 cases with activating HER2 mutations and 1 with a novel HER2–GRB7 gene fusion. This fusion links the HER2 tyrosine kinase domain to the GRB7 src homology 2 (SH2) domain. Clin Cancer Res; 19(13); 3331–3. ©2013 AACR.
Predicting Outcome by Images?
Authors: De Ruysscher Dirk 
Published: May 2013

Abstract
Features from CT, MRI, and PET scans are related to survival of patients with non–small cell lung carcinoma. Individualized image-based tissue characterization allows a whole body view of all tumor deposits and organs at risk. The time is ripe to embark on huge international studies aiming to validate and implement this technology in clinical practice. Clin Cancer Res; 19(13); 3334–6. ©2013 AACR.
Metabolic and Functional Genomic Studies Identify Deoxythymidylate Kinase as a Target in LKB1-Mutant Lung Cancer
Authors: Liu Yan , Marks Kevin , Cowley Glenn S. , Carretero Julian , Liu Qingsong , Nieland Thomas J.F. , Xu Chunxiao , Cohoon Travis J. , Gao Peng , Zhang Yong , Chen Zhao , Altabef Abigail B. , Tchaicha Jeremy H. , Wang Xiaoxu , Choe Sung , Driggers Edward M. , Zhang Jianming , Bailey Sean T. , Sharpless Norman E. , Hayes D. Neil , Patel Nirali M. , Janne Pasi A. , Bardeesy Nabeel , Engelman Jeffrey A. , Manning Brendan D. , Shaw Reuben J. , Asara John M. , Scully Ralph , Kimmelman Alec , Byers Lauren A. , Gibbons Don L. , Wistuba Ignacio I. , Heymach John V. , Kwiatkowski David J. , Kim William Y. , Kung Andrew L. , Gray Nathanael S. , Root David E. , Cantley Lewis C. , Wong Kwok-Kin 
Published: May 2013

Abstract
The LKB1/STK11 tumor suppressor encodes a serine/threonine kinase, which coordinates cell growth, polarity, motility, and metabolism. In non–small cell lung carcinoma, LKB1 is somatically inactivated in 25% to 30% of cases, often concurrently with activating KRAS mutations. Here, we used an integrative approach to define novel therapeutic targets in KRAS-driven LKB1-mutant lung cancers. High-throughput RNA interference screens in lung cancer cell lines from genetically engineered mouse models driven by activated KRAS with or without coincident Lkb1 deletion led to the identification of Dtymk, encoding deoxythymidylate kinase (DTYMK), which catalyzes dTTP biosynthesis, as synthetically lethal with Lkb1 deficiency in mouse and human lung cancer lines. Global metabolite profiling showed that Lkb1-null cells had a striking decrease in multiple nucleotide metabolites as compared with the Lkb1–wild-type cells. Thus, LKB1-mutant lung cancers have deficits in nucleotide metabolism that confer hypersensitivity to DTYMK inhibition, suggesting that DTYMK is a potential therapeutic target in this aggressive subset of tumors.
Significance: Using cell lines derived from the lung cancers occurring in genetically engineered mice, we conducted an integrative genome-wide short hairpin RNA and metabolite screen to identify DTYMK as a potential therapeutic target in Kras/Lkb1–mutant lung cancer. We believe that DTYMK is tractable for the development of novel therapeutics, and show an integrative approach to target identification that reduces false-positive candidates and should have broad applicability for the development of targeted therapeutics. Cancer Discov; 3(8); 870–9. ©2013 AACR.
See related commentary by Marcus and Khuri, p. 843
This article is highlighted in the In This Issue feature, p. 826
Analysis of the Costs and Payments of a Coordinated Stroke Center and Regional Stroke Network
Authors: Rymer Marilyn M. , Armstrong Edward P. , Meredith Neil R. , Pham Sissi V. , Thorpe Kevin , Kruzikas Denise T. 
Published: May 2013

Background and Purpose—
An earlier study demonstrated significantly improved access, treatment, and outcomes after the implementation of a progressive, comprehensive stroke program at a tertiary care community hospital, Saint Luke’s Neuroscience Institute (SLNI). This study evaluated the costs associated with implementing such a program.

Methods—
Retrospective analysis of total hospital costs and payments for treating patients with ischemic stroke at SLNI (n=1570) as program enhancement evolved over time (2005, 2007, and 2010) and compared with published national estimates. Analyses were stratified by patient demographic characteristics, patient outcomes, treatments, time, and comorbidities.

Results—
Controlling for inflation, there was no difference in SLNI total costs between 2005 and either 2007 or 2010, suggesting that while SLNI provided an increased level of services, any additional expenditures were offset by efficiencies. SLNI total costs were slightly lower than published benchmarks. Consistent with previous stroke care cost estimates, the median overall differential between total hospital costs and payments for all ischemic stroke cases was negative.

Conclusions—
SLNI total costs remained consistent over time and were slightly lower than previously published estimates, suggesting that a focused, streamlined stroke program can be implemented without a significant economic impact. This finding further demonstrates that providing comprehensive stroke care with improved access and treatment may be financially feasible for other hospitals.
Eritrean Pentecostals as Asylum Seekers in Britain
Authors: Anderson Allan Heaton 
Published: May 2013

Abstract
This article explores the background and issues relating to the plight of Eritrean Pentecostal asylum seekers, and is based on background literature on the Eritrean context and interviews with Eritrean asylum seekers in the UK. It explores the historical, political, and religious context of Eritrea and analyses the challenges presented to British immigration officials by the presence of Eritrean asylum seekers who claim to be persecuted for their Pentecostal faith. The article examines the processes from the perspective of personal narratives of asylum seekers, their reasons for fleeing their country, the documents and statements used to deny them asylum in the application process, and the characteristics of their faith that are often overlooked.