bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the efficacy and safety of a Chinese herbal formula (RCM-106) for atopic dermatitis: study protocol for a randomised, double-blind, placebo-controlled trial in children
Authors: Tan Hsiewe Ying , Zhang Anthony L , Xue Charlie C , Chen Dacan , Da Costa Cliff , Lenon George B 
Published: January 2014

IntroductionAtopic dermatitis is a chronic, inflammatory skin rash that greatly affects quality of life. The current therapies are inadequate in managing atopic dermatitis and often have associated adverse effects or drug tolerance development. Chinese medicine is expected to have promising prospects in the management of atopic dermatitis and recent studies have shown encouraging results. This study aims to evaluate the efficacy and safety of a newly formulated Chinese herbal formula, RMIT Chinese Medicine-106 (RCM-106), in the management of moderate-to-severe atopic dermatitis in children aged 6–18 years.MethodsThe study is a randomised, double-blind, placebo-controlled, parallel-armed clinical trial. Participant, investigator and assessors will remain blinded to the treatment assignment until after the study has been completed. After a 2-week run-in period, 90 participants will be randomised, using block randomised sequences generated by computer, to receive either RCM-106 or matching placebo capsules, twice daily, for a treatment period of 8 weeks and followed up for 4 weeks. Primary outcome measures include the evaluation of disease severity and extent using two validated scoring instruments—Scoring Atopic Dermatitis (SCORAD) and Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD). Secondary outcome measures include the evaluation of quality of life using the Children's Dermatology Life Quality Index (CDLQI); occurrence of adverse events and total usage of other therapies as recorded in the participants’ daily diary and laboratory studies which include eosinophil count, total IgE, full blood count and liver and kidney function tests. Intention-to-treat analysis will be applied to all data analyses.Ethics and disseminationThis trial has received human ethics approval from the Human Research Ethics Committee (HREC) of RMIT University (Project number 15/12). The study findings will be published in peer-reviewed journals and presented at the national and international conferences.Trial registrationAustralia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612001181897. TGA CTN Scheme: Trial number 2012/0713; Protocol number 15/12.
Can education alter attitudes, behaviour and knowledge about organ donation? A pretest–post-test study
Authors: McGlade Donal , Pierscionek Barbara 
Published: January 2014

ObjectiveThe emergence of evidence suggests that student nurses commonly exhibit concerns about their lack of knowledge of organ donation and transplantation. Formal training about organ donation has been shown to positively influence attitude, encourage communication and registration behaviours and improve knowledge about donor eligibility and brain death. The focus of this study was to determine the attitude and behaviour of student nurses and to assess their level of knowledge about organ donation after a programme of study.DesignA quantitative questionnaire was completed before and after participation in a programme of study using a pretest–post-test design.SettingParticipants were recruited from a University based in Northern Ireland during the period from February to April 2011.Participants100 preregistration nurses (female : male=96 : 4) aged 18–50 years (mean (SD) 24.3 (6.0) years) were recruited.ResultsParticipants’ knowledge improved over the programme of study with regard to the suitability of organs that can be donated after death, methods available to register organ donation intentions, organ donation laws, concept of brain death and the likelihood of recovery after brain death. Changes in attitude postintervention were also observed in relation to participants’ willingness to accept an informed system of consent and with regard to participants’ actual discussion behaviour.ConclusionsThe results provide support for the introduction of a programme that helps inform student nurses about important aspects of organ donation.
Long-term evolution of renal function in patients with type 2 diabetes mellitus: a registry-based retrospective cohort study
Authors: Goderis Geert , Van Pottelbergh Gijs , Truyers Carla , Van Casteren Viviane , De Clercq Etienne , Van Den Broeke Carine , Buntinx Frank 
Published: January 2014

ObjectivesTo picture the 10-year evolution of renal function in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) and to describe the risk factors for severe decline.SettingPrimary registration network with 97 general practitioners working in 55 practices sending routinely collected patient data.ParticipantsFrom the database, we selected all patients aged 40 years or older with T2DM and at least two creatinine measurements in two different years with an interval of at least 3 months. Based on the last available value of estimated glomerular filtration rate calculated by the modification of diet in renal disease (MDRD) equation, patients were divided into grades of CKD. Severe decline (decline of >4 mL/min/year) and ‘certain drop’ (CD, year-to-year decline >10 mL/min) were determined in patients with CKD. Determinants of severe decline and CD were investigated with logistic regression and longitudinal logistic regression analysis, respectively.Primary outcome measureKidney function (MDRD).Results4041 patients, 1980 women, were included. The mean age was 71 years, mean diabetes duration was 7.7 years; 1514 (38%) suffered from CKD, 231 (15%) presented with severe decline and 18% of the patients with CKD presented with two or more CDs. Younger age, male gender, mean glycated haemoglobin and a higher number of CDs were significantly associated with the presence of severe decline (p<0.05); statins and higher diastolic blood pressure were significantly associated with the absence of severe decline (p<0.001). ACE inhibitors, other antihypertensive drugs and antidiabetic drugs including insulin therapy were specific determinants of CD.ConclusionsCKD is highly prevalent in patients with T2DM; a minority of patients evolve into severe decline that is associated with younger age, male gender, ‘CD’ and manageable factors such as blood pressure, blood glucose, associated drugs prescriptions and statin therapy. Further prospective observational and experimental research is needed to clarify the nature of those associations.
Prevalence of ocular fundus pathology with type 2 diabetes in a Chinese urban community as assessed by telescreening
Authors: Liu Lei , Geng Jin , Wu Jingyang , Yuan Zhe , Lian Jie , Desheng Huang , Chen Lei 
Published: January 2014

ObjectiveTo describe the telescreening model and assess the prevalence of ocular fundus pathology in patients with type 2 diabetes within a Chinese urban community.DesignCommunity-based cross-sectional study.SettingHealthcare centre of Fengyutan Community, Shenyang, China.ParticipantsA total 528 patients (287 females) with type 2 diabetes mellitus (DM) were randomly recruited using health files from the healthcare centre of Fengyutan community between 8 October and 20 November 2012.Main outcome measuresSigns of any diabetic retinopathy (DR), signs of glaucoma and signs of age-related macular degeneration (AMD).ResultsThe main ocular fundus pathologies were DR (75 patients, 14.20%), 65 (86.67%) cases of which were newly detected, AMD (57 patients, 10.79%) and glaucoma (63 patients, 11.93%). The risk factors for fundus pathology were long duration of diabetes (OR 2.31, 95% CI 1.87 to 2.56), and higher fasting plasma glucose (OR 3.64, 95% CI 1.81 to 5.21) and glycated haemoglobin (HbA1c) levels (OR 3.83, 95% CI 1.87 to 6.35).ConclusionsThere was a high prevalence of fundus pathology among patients with type 2 diabetes, and in most of the cases, this was newly detected. Community screening for fundus pathology among patients with a long duration of type 2 diabetes and high fasting plasma glucose and HbA1c levels using a telescreening model will provide an effective strategy for the prevention and treatment of fundus pathology.
Nicotine-Mediated Cell Proliferation and Tumor Progression in Smoking-Related Cancers
Authors: Schaal Courtney , Chellappan Srikumar P. 
Published: January 2014

Abstract
Tobacco smoke contains multiple classes of established carcinogens including benzo(a)pyrenes, polycyclic aromatic hydrocarbons, and tobacco-specific nitrosamines. Most of these compounds exert their genotoxic effects by forming DNA adducts and generation of reactive oxygen species, causing mutations in vital genes such as K-Ras and p53. In addition, tobacco-specific nitrosamines can activate nicotinic acetylcholine receptors (nAChR) and to a certain extent β-adrenergic receptors (β-AR), promoting cell proliferation. Furthermore, it has been demonstrated that nicotine, the major addictive component of tobacco smoke, can induce cell-cycle progression, angiogenesis, and metastasis of lung and pancreatic cancers. These effects occur mainly through the α7-nAChRs, with possible contribution from the β-ARs and/or epidermal growth factor receptors. This review article will discuss the molecular mechanisms by which nicotine and its oncogenic derivatives such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N-nitrosonornicotine induce cell-cycle progression and promote tumor growth. A variety of signaling cascades are induced by nicotine through nAChRs, including the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway, phosphoinositide 3-kinase/AKT pathway, and janus-activated kinase/STAT signaling. In addition, studies have shown that nAChR activation induces Src kinase in a β-arrestin-1-dependent manner, leading to the inactivation of Rb protein and resulting in the expression of E2F1-regulated proliferative genes. Such nAChR-mediated signaling events enhance the proliferation of cells and render them resistant to apoptosis induced by various agents. These observations highlight the role of nAChRs in promoting the growth and metastasis of tumors and raise the possibility of targeting them for cancer therapy. Mol Cancer Res; 12(1); 14–23. ©2014 AACR.
Statins and Aspirin for Chemoprevention in Barrett's Esophagus: Results of a Cost-Effectiveness Analysis
Authors: Choi Sung Eun , Perzan Katherine E. , Tramontano Angela C. , Kong Chung Yin , Hur Chin 
Published: January 2014

Abstract
Data suggest that aspirin, statins, or a combination of the two drugs may lower the progression of Barrett's esophagus to esophageal adenocarcinoma. However, aspirin is associated with potential complications such as gastrointestinal bleeding and hemorrhagic stroke, and statins are associated with myopathy. We developed a simulation disease model to study the effectiveness and cost effectiveness of aspirin and statin chemoprevention against esophageal adenocarcinoma. A decision analytic Markov model was constructed to compare four strategies for Barrett's esophagus management; all regimens included standard endoscopic surveillance regimens: (i) endoscopic surveillance alone, (ii) aspirin therapy, (iii) statin therapy, and (iv) combination therapy of aspirin and statin. Endpoints evaluated were life expectancy, quality-adjusted life years (QALY), costs, and incremental cost-effectiveness ratios (ICER). Sensitivity analysis was performed to determine the impact of model input uncertainty on results. Assuming an annual progression rate of 0.33% per year from Barrett's esophagus to esophageal adenocarcinoma, aspirin therapy was more effective and cost less than (dominated) endoscopic surveillance alone. When combination therapy was compared with aspirin therapy, the ICER was $158,000/QALY, which was above our willingness-to-pay threshold of $100,000/QALY. Statin therapy was dominated by combination therapy. When higher annual cancer progression rates were assumed in the model (0.5% per year), combination therapy was cost-effective compared with aspirin therapy, producing an ICER of $96,000/QALY. In conclusion, aspirin chemoprevention was both more effective and cost less than endoscopic surveillance alone. Combination therapy using both aspirin and statin is expensive but could be cost-effective in patients at higher risk of progression to esophageal adenocarcinoma. Cancer Prev Res; 7(3); 341–50. ©2013 AACR.
Disruption of CD8+ Treg Activity Results in Expansion of T Follicular Helper Cells and Enhanced Antitumor Immunity
Authors: Alvarez Arias Diana A. , Kim Hye-Jung , Zhou Penghui , Holderried Tobias A.W. , Wang Xuan , Dranoff Glenn , Cantor Harvey 
Published: January 2014

Abstract
Tumor growth is associated with the inhibition of host antitumor immune responses that can impose serious obstacles to cancer immunotherapy. To define the potential contribution of Qa-1–restricted CD8 regulatory T cells (Treg) to the development of tumor immunity, we studied B6.Qa-1 D227K mice that harbor a point mutation in the MHC class Ib molecule Qa-1 that impairs CD8 Treg suppressive activity. Here, we report that the growth of B16 melanoma is substantially delayed in these Qa-1–mutant mice after therapeutic immunization with B16 melanoma cells engineered to express granulocyte macrophage colony-stimulating factor compared with Qa-1 B6-WT controls. Reduced tumor growth is associated with enhanced expansion of follicular T helper cells, germinal center B cells, and high titers of antitumor autoantibodies, which provoke robust antitumor immune responses in concert with tumor-specific cytolytic T cells. Analysis of tumor-infiltrating T cells revealed that the Qa-1 DK mutation was associated with an increase in the ratio of CD8+ T effectors compared with CD8 Tregs. These data suggest that the CD8+ T effector–Treg ratio may provide a useful prognostic index for cancer development and raise the possibility that depletion or inactivation of CD8 Tregs represents a potentially effective strategy to enhance antitumor immunity. Cancer Immunol Res; 2(3); 207–16. ©2013 AACR.
Establishment of Tumor-Associated Immunity Requires Interaction of Heat Shock Proteins with CD91
Authors: Zhou Yu Jerry , Messmer Michelle Nicole , Binder Robert Julian 
Published: January 2014

AbstractHost antitumor adaptive immune responses are generated as a result of the body's immunosurveillance mechanisms. How the antitumor immune response is initially primed remains unclear, given that soluble tumor antigens generally are quantitatively insufficient for cross-priming and tumors generally lack the classical pathogen-associated molecular patterns to activate costimulation and initiate cross-priming. We explored the interaction of the tumor-derived heat shock proteins (HSP) with their common receptor (CD91) on antigen-presenting cells (APC) as a mechanism for host-priming of T-cell–mediated antitumor immunity. Using targeted genetic disruption of the interaction between HSPs and CD91, we demonstrated that specific ablation of CD91 in APCs prevented the establishment of antitumor immunity. The antitumor immunity was also inhibited when the transfer of tumor-derived HSPs to APCs was prevented using an endogenous inhibitor of CD91. Inhibition was manifested in a reduction of cross-presentation of tumor-derived antigenic peptides in the lymph nodes, providing a molecular basis for the observed immunity associated with tumor development. Our findings demonstrate that early in tumor development, the HSP-CD91 pathway is critical for the establishment of antitumor immunity. Cancer Immunol Res; 2(3); 217–28. ©2013 AACR.
Transforming Growth Factor-β and Inflammation in Vascular (Type IV) Ehlers–Danlos Syndrome
Authors: Morissette Rachel , Schoenhoff Florian , Xu Zhi , Shilane David A. , Griswold Benjamin F. , Chen Wuyan , Yang Jiandong , Zhu Jie , Fert-Bober Justyna , Sloper Leslie , Lehman Jason , Commins Natalie , Van Eyk Jennifer E. , McDonnell Nazli B. 
Published: January 2014

Background—

Vascular Ehlers–Danlos syndrome (VEDS) causes reduced life expectancy because of arterial dissections/rupture and hollow organ rupture. Although the causative gene,
COL3A1
, was identified >20 years ago, there has been limited progress in understanding the disease mechanisms or identifying treatments.

Methods and Results—

We studied inflammatory and transforming growth factor-β (TGF-β) signaling biomarkers in plasma and from dermal fibroblasts from patients with VEDS. Analyses were done in terms of clinical disease severity, genotype–phenotype correlations, and body composition and fat deposition alterations. VEDS subjects had increased circulating TGF-β1, TGF-β2, monocyte chemotactic protein-1, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and leptin and decreased interleukin-8 versus controls. VEDS dermal fibroblasts secreted more TGF-β2, whereas downstream canonical/noncanonical TGF-β signaling was not different. Patients with
COL3A1
exon skipping mutations had higher plasma intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and VEDS probands had abnormally high plasma C-reactive protein versus affected patients identified through family members before any disease manifestations. Patients with VEDS had higher mean platelet volumes, suggesting increased platelet turnover because of ongoing vascular damage, as well as increased regional truncal adiposity.

Conclusions—
These findings suggest that VEDS is a systemic disease with a major inflammatory component. C-reactive protein is linked to disease state and may be a disease activity marker. No changes in downstream TGF-β signaling and increased platelet turnover suggest that chronic vascular damage may partially explain increased plasma TGF-β1. Finally, we found a novel role for dysregulated TGF-β2, as well as adipocyte dysfunction, as demonstrated through reduced interleukin-8 and elevated leptin in VEDS.
Long-Term Arrhythmia-Free Survival in Patients With Severe Left Ventricular Dysfunction and No Inducible Ventricular Tachycardia After Myocardial Infarction
Authors: Zaman Sarah , Narayan Arun , Thiagalingam Aravinda , Sivagangabalan Gopal , Thomas Stuart , Ross David L. , Kovoor Pramesh 
Published: January 2014

Background—
A negative electrophysiology study (EPS) may delineate a subgroup of patients with severely impaired left ventricular ejection fraction (LVEF) whose care can be safely managed long-term without an implantable cardioverter-defibrillator.

Methods and Results—

Consecutive patients treated with primary percutaneous coronary intervention for ST-segment–elevation myocardial infarction underwent early (median 4 days) LVEF assessment. Patients with LVEF ≤40% underwent EPS. A prophylactic implantable cardioverter-defibrillator was implanted for a positive (inducible monomorphic ventricular tachycardia) but not a negative (no inducible ventricular tachycardia or inducible ventricular fibrillation/flutter) EPS result. Patients who would have become eligible for a late primary prevention implantable cardioverter-defibrillator with LVEF ≤30% or ≤35% with New York Heart Association class II/III heart failure were included and analyzed according to EPS result. Patients with LVEF >40%, ineligible for EPS, were followed up as control subjects (n=1286). The primary end point was survival free of death or arrhythmia (resuscitated cardiac arrest or sustained ventricular tachycardia/ventricular fibrillation). EPS performed in 128 patients with LVEF ≤30% or with LVEF ≤35% and heart failure was negative in 63% (n=80) and positive in 37% (n=48). Implantable-cardioverter defibrillators were implanted in <0.1%, 4%, and 90% of control, EPS-negative, and EPS-positive patients, respectively. The distribution of time to death or arrhythmia was comparable in control patients and EPS-negative patients with LVEF ≤30% or with LVEF ≤35% and heart failure (
P
=0.738), who both differed significantly from EPS-positive patients (
P
<0.001). At 3 years, 91.8±3.2%, 93.4±1.0%, and 62.7±7.5% of control, EPS-negative, and EPS-positive patients were free of death or arrhythmia, respectively.

Conclusions—
Revascularized patients with ST-segment–elevation myocardial infarction with severely impaired left ventricular function but no inducible ventricular tachycardia have a favorable long-term prognosis without the protection of an implantable cardioverter-defibrillator.
Predictive Discomfort in Single- and Combined-Axis Whole-Body Vibration Considering Different Seated Postures
Authors: DeShaw Jonathan , Rahmatalla Salam 
Published: January 2014

Objective: The aim of this study was to develop a predictive discomfort model in single-axis, 3-D, and 6-D combined-axis whole-body vibrations of seated occupants considering different postures. Background: Non-neutral postures in seated whole-body vibration play a significant role in the resulting level of perceived discomfort and potential long-term injury. The current international standards address contact points but not postures. Method: The proposed model computes discomfort on the basis of static deviation of human joints from their neutral positions and how fast humans rotate their joints under vibration. Four seated postures were investigated. For practical implications, the coefficients of the predictive discomfort model were changed into the Borg scale with psychophysical data from 12 volunteers in different vibration conditions (single-axis random fore-aft, lateral, and vertical and two magnitudes of 3-D). The model was tested under two magnitudes of 6-D vibration. Results: Significant correlations ( R2 = .93) were found between the predictive discomfort model and the reported discomfort with different postures and vibrations. The ISO 2631-1 correlated very well with discomfort ( R2 = .89) but was not able to predict the effect of posture. Conclusion: Human discomfort in seated whole-body vibration with different non-neutral postures can be closely predicted by a combination of static posture and the angular velocities of the joint. Application: The predictive discomfort model can assist ergonomists and human factors researchers design safer environments for seated operators under vibration. The model can be integrated with advanced computer biomechanical models to investigate the complex interaction between posture and vibration.