Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of venous thromboembolism with the erythropoiesis-stimulating agents (ESAs) for the treatment of cancer-associated anemia: a meta-analysis of randomized control trials.

BACKGROUND In anemic patients receiving myelosuppressive chemotherapy, erythropoiesis-stimulating agents (ESAs) raise hemoglobin levels and reduce transfusion requirements, but ESA-related safety concerns exist. To evaluate the overall risk of venous thromboembolism (VTE) associated with the use of ESAs, a systematic review and meta-analysis of published randomized controlled trials (RCT) was performed. METHODS The databases of PubMed and Web of Science were searched from January 1966 until December 2012 and abstracts presented at American Society of Clinical Oncology conferences held between January 2000 and December 2012 were searched to identify relevant clinical trials. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated. RESULTS Data from a total of 11,632 patients with cancer in 50 RCTs were identified and included for meta-analysis. Among those patients receiving ESAs, the summary incidences of all-grade VTE were 7.62%. Patients with cancer who received ESAs had increased VTE risks (482 events among 6,238 patients treated with ESA vs. 269 events among 5,394 control patients; RR=1.75; 95% CI, 1.49-2.05). The highest risk of VET was found in patients with ovarian and cervical cancer for 2.45 (1.12-5.33). CONCLUSIONS The use of ESAs was significantly associated with an increased risk of developing VTE in cancer patients receiving this drug. The risks of VTE may vary with various tumor types.
Effect of nutritional restriction in early pregnancy on isolated femoral artery function in mid‐gestation fetal sheep

Unbalanced maternal nutrition affects fetal endocrine and cardiovascular systems, sometimes accompanied by changes in growth, although this is usually in late gestation. We determined the effect of moderate restriction for the first half of gestation of maternal dietary protein, or of total calorific intake on isolated resistance artery function of mid‐gestation fetal sheep. Welsh Mountain ewes were nutritionally restricted by 30 % of the recommended nutrient intake (globally restricted) or 30 % of the recommended protein intake (protein‐restricted), compared to control ewes fed 100 % of recommended nutrient intake, for ~12 days prior to conception and for the subsequent 70 days of gestation. At mid‐gestation, fetal and placental weights were similar in all dietary groups. In isolated femoral arteries, the response curve to noradrenaline was reduced in protein‐restricted group fetuses (P < 0.05). Maximal relaxation (P < 0.01) and sensitivity (P < 0.05) to acetylcholine were markedly reduced in protein‐restricted group fetuses, and to a smaller extent in globally restricted group fetuses (response curve, P < 0.05). The dilator response (P < 0.05) and sensitivity (P < 0.05) to the α2 agonist UK14304 was lower in protein‐, but not in globally restricted group fetuses. The response (P < 0.05) and sensitivity (P < 0.05) to the nitric oxide donor sodium nitroprusside were reduced in protein‐restricted group fetuses compared to controls. Our data show that dietary imbalance, in particular restricted protein, of the ewe can produce blunting of endothelial‐dependent and ‐independent relaxation in systemic arteries from the mid‐gestation fetus. These changes may precede perturbed late‐gestation fetal and postnatal cardiovascular control.
Characterization of the immune escape phenotype of human gastric cancers with and without high‐frequency microsatellite instability

Gastric cancers with and without high‐frequency microsatellite instability (MSI‐H) represent distinctive pathways of carcinogenesis. The aim of this study was to clarify if human leukocyte antigen (HLA) class I antigen subunits and antigen processing machinery (APM) components are differentially downregulated in these two groups of tumours. Using reverse transcription PCR (RT‐PCR), loss of heterozygosity (LOH) analysis, methylation‐specific PCR (MSP), DNA sequencing, immunohistochemistry, and flow cytometry, we analysed expression and/or alteration of HLA class I antigen subunits and APM components, including low molecular weight polypeptide proteasome subunit (LMP)2, LMP7, LMP10, transporter associated with antigen processing (TAP)1, TAP2, tapasin, proteasome activator (PA) 28α, and PA28β in two stage‐matched panels of 30 MSI‐H and 30 microsatellite stable (MSS) gastric cancers. Mutations at coding microsatellites (cMS) located within β2‐microglobulin (β2m) and genes encoding APM components, including endoplasmic reticulum (ER) chaperone protein genes, such as calnexin, SEC63, SEC31, and P4HB (p55), were also analysed. HLA class Ia transcripts were totally downregulated in 18.3% of cancer cases. Locus‐specific downexpression of HLA‐A, ‐B, and ‐C was detected in 41.7%, 45.0%, and 31.7% of cases. Loss of HLA‐A was significantly more frequent in MSI‐H cancers. The LOH ratios of the HLA‐A, ‐B, and ‐C loci microsatellite markers were relatively low: 5/32 (15.6%) for D6S306, 4/32 (12.5%) for D6S258, 4/33 (12.1%) for D6S273, and 4/30 (13.3%) for D6S1666. Methylation of HLA‐A, ‐B, and ‐C was detected in 38.3%, 40.0%, and 28.3% of cases. A significant association between methylation and reduction in expression was observed in gastric cancer tissues. Mutations at cMS of β2m and APM components were detected in 3.3–46.7% of MSI‐H cancers but in none of MSS cancers. These data show that gastric cancers have various defects in HLA class I antigen subunits and APM components and that the MSI phenotype is associated with frequent HLA‐A inactivation and frameshift mutations of the β2m and APM genes. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
GG-02 Epigenetic reprogramming in NAïVE CD4+ T cells favouring T cell activation and NON-TH1 effector T cell immune response as an early event in lupus flares

Background Systemic lupus erythematosus is a relapsing autoimmune disease that affects multiple organ systems. T cells play an important role in the pathogenesis of lupus, however, early T cell events triggering disease flares are incompletely understood. We studied DNA methylation in naïve CD4+ T cells from lupus patients to determine if epigenetic remodelling in CD4+ T cells is an early event in lupus flares. Materials and methods A total of 74 lupus patients with disease activity ranging from 0–18 as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were included in this study. Naïve CD4+ T cells were isolated from peripheral blood samples and DNA extracted for genome-wide methylation assessment. RNA was also extracted from a subset of patients to determine the relationship between epigenetic changes and transcriptional activity using RNA sequencing and microRNA arrays. Results We demonstrate that naïve CD4+ T cells in lupus undergo an epigenetic pro-inflammatory shift implicating effector T cell responses in lupus flare. This epigenetic landscape change occurs without expression changes of corresponding genes, and poises naïve CD4+ T cells for Th2, Th17, and Tfh immune responses, and opposes inhibitory TGF-β signalling. Bioinformatics analyses indicate that the epigenetic modulator EZH2 might be playing an important role in shifting the epigenetic landscape with increased disease activity in lupus naïve CD4+ T cells. Further, the expression of miR26a and miR101, which are sensitive to glucose availability and target EZH2, negatively correlated with disease activity in lupus patients. Conclusion An epigenetic landscape shift in naïve CD4+ T cells that favours T cell activation and non-Th1 immune responses predates transcriptional activity and correlates with lupus activity. A role for EZH2 dysregulation in triggering lupus flares warrants further investigation. The proposed T cell epigenetic model of disease flare in lupus patients is depicted in Figure 1. Abstract GG-02 Figure 1 T cell epigenetic model of disease flares in lupus Acknowledgements This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R01AI097134.
Pedagogy for Autonomy in Modern Languages Education: Theory, practice, and teacher education

This book has three aims: to examine critical issues in current thinking about learner autonomy and teacher education; to give examples of a number of classroom approaches to the development of learner autonomy in the EuroPAL countries; and to present the work of various teacher educators and research that focuses on teacher development for learner autonomy. Concerned exclusively with language teaching and learning in secondary schools, the book is one of the products of the EuroPAL project, funded by the SOCRATES programme.
Using writing composition pedagogy in an introductory teacher education practicum to learn about the motivations, journeys, and understandings of preservice teachers

Over the last third of the twentieth century, best practice in America's public schools has evolved from a focus on the teacher's behavior in presenting material to a focus on whether and how students learn. Over that same period, writing composition pedagogy has focused on the emphasis on students' growth and development as they think reflectively, write drafts, and self-monitor. Integrating writing composition pedagogy in the education of preservice teachers, I use Exploring Teaching, a learner-centered introductory course in teacher education that I teach, as the specific context of my inquiry. As my students write Dear Classmates Letters, portfolio reflections, and self-evaluations, I seek to learn what teacher educators can do to effectively mentor students exploring teaching, challenge their assumptions about teaching, construct introductory courses in education, and create new courses in the program of study in teacher education to meet the individual needs of students as they explore teaching. By examining the motivations of preservice teachers as they explore the teaching life, teacher educators can learn how to tailor their mentoring to the needs of individual students. By discerning whether the Exploring Teaching course changes preservice teachers' orientation to teaching, teacher educators can construct such introductory education classes to effectively mentor those in transformation; to appropriately challenge those preservice teachers who enter with preconceived assumptions about the teaching life so that their decisions to teach are well informed and realistic. By learning what preservice teachers understand about the roles of teachers, teacher educators can mentor individual students to respond to their existing images of teaching and clear up misconceptions; to construct classes that engage students in dialogue and discussion that challenge, critique, and/or further explore individual assumptions about teaching; to help students understand more clearly what teachers do; and, if warranted, address the construction of additional courses in the teacher education program of study to meet the individual needs of students.
Activity of Broadly Neutralizing Antibodies, Including PG9, PG16, and VRC01, against Recently Transmitted Subtype B HIV-1 Variants from Early and Late in the Epidemic

ABSTRACT For the development of a neutralizing antibody-based human immunodeficiency virus type 1 (HIV-1) vaccine, it is important to characterize which antibody specificities are most effective against currently circulating HIV-1 variants. We recently reported that HIV-1 has become more resistant to antibody neutralization over the course of the epidemic, and we here explore whether this increased neutralization resistance is also observed for the newly identified broadly neutralizing antibodies (BrNAbs) PG9, PG16, and VRC01. Furthermore, we performed a comprehensive analysis of the neutralizing sensitivity of currently circulating recently transmitted subtype B viruses to the currently most known BrNAbs. Virus variants isolated less than 6 months after seroconversion from individuals who seroconverted between 2003 and 2006 (n = 21) were significantly more resistant to neutralization by VRC01 than viruses from individuals who seroconverted between 1985 and 1989 (n = 14). In addition, viruses from contemporary seroconverters tended to be more resistant to neutralization by PG16, which coincided with the presence of more mutations at positions in the viral envelope that may potentially influence neutralization by this antibody. Despite this increased neutralization resistance, all recently transmitted viruses from contemporary seroconverters were sensitive to at least one BrNAb at concentrations of ≤5 μg/ml, with PG9, PG16, and VRC01 showing the greatest breadth of neutralization at lower concentrations. These results suggest that a vaccine capable of eliciting multiple BrNAb specificities will be necessary for protection of the population against HIV-1 infection.
Long- and short-term variability of automated perimetry results in patients with optic neuritis and healthy subjects.

OBJECTIVE To measure the short- and long-term variability of automated perimetry in patients with optic neuritis and normal subjects. DESIGN Prospective case-control design of patients with recovered optic neuritis with intraday and interday repetitions to obtain robust variability measurements. Entry criteria included a corrected pattern SD that was worse than the normal 5% probability level and a mean deviation worse than -3 dB but better than -20 dB. Five Humphrey 30-2 full threshold tests were administered during a 7-hour period (1 test every 2 hours) on the same day and at the same periods on 5 separate days. SUBJECTS Seventeen patients with recovered optic neuritis and 10 healthy subjects of similar age. MAIN OUTCOME MEASURES Short-term variability and long-term variability for global visual field data. RESULTS Patients with optic neuritis demonstrated variations in visual field sensitivity that were outside the entire range of variability for normal controls. These variations occurred for multiple tests performed on the same day at specific times and for tests performed at specific times on different days. There were no consistent patterns of sensitivity changes that could be attributed to time of day. The most dramatic fluctuations occurred in a patient whose visual fields varied from normal to a hemianopic defect from one week to another and from a partial quadrant loss to a hemianopic defect at different times on the same day. Seven of the patients with optic neuritis also demonstrated intermittent vertical step defects. CONCLUSIONS Patients with resolved optic neuritis can have large variations in visual field results on different days and at different times on the same day. The variations affect both the severity and the pattern of visual field loss and do not appear to be consistent across patients. These data indicate that care must be taken when automated visual field results in patients with optic neuritis are interpreted. Distinguishing systematic changes in sensitivity from variability requires more than a comparison of the current visual field with the most recent previous visual field.
PCR and Omics Based Techniques to Study the Diversity, Ecology and Biology of Anaerobic Fungi: Insights, Challenges and Opportunities

Anaerobic fungi (phylum Neocallimastigomycota) are common inhabitants of the digestive tract of mammalian herbivores, and in the rumen, can account for up to 20% of the microbial biomass. Anaerobic fungi play a primary role in the degradation of lignocellulosic plant material. They also have a syntrophic interaction with methanogenic archaea, which increases their fiber degradation activity. To date, nine anaerobic fungal genera have been described, with further novel taxonomic groupings known to exist based on culture-independent molecular surveys. However, the true extent of their diversity may be even more extensively underestimated as anaerobic fungi continue being discovered in yet unexplored gut and non-gut environments. Additionally many studies are now known to have used primers that provide incomplete coverage of the Neocallimastigomycota. For ecological studies the internal transcribed spacer 1 region (ITS1) has been the taxonomic marker of choice, but due to various limitations the large subunit rRNA (LSU) is now being increasingly used. How the continued expansion of our knowledge regarding anaerobic fungal diversity will impact on our understanding of their biology and ecological role remains unclear; particularly as it is becoming apparent that anaerobic fungi display niche differentiation. As a consequence, there is a need to move beyond the broad generalization of anaerobic fungi as fiber-degraders, and explore the fundamental differences that underpin their ability to exist in distinct ecological niches. Application of genomics, transcriptomics, proteomics and metabolomics to their study in pure/mixed cultures and environmental samples will be invaluable in this process. To date the genomes and transcriptomes of several characterized anaerobic fungal isolates have been successfully generated. In contrast, the application of proteomics and metabolomics to anaerobic fungal analysis is still in its infancy. A central problem for all analyses, however, is the limited functional annotation of anaerobic fungal sequence data. There is therefore an urgent need to expand information held within publicly available reference databases. Once this challenge is overcome, along with improved sample collection and extraction, the application of these techniques will be key in furthering our understanding of the ecological role and impact of anaerobic fungi in the wide range of environments they inhabit.
The Impacts of Service Failure and Recovery Efforts on Airline Customers’ Emotions and Satisfaction

Using online customer reviews for airline services, this study examines the impacts of various attributes of airline service failures and subsequent recovery actions on customer consumption emotions, satisfaction, and recommendation likelihood through text mining, sentiment analysis, and path analysis. Findings suggest that causes, magnitude, and consequences of service failures influence customers’ positive and negative emotions. Providing compensation for the current trip, either monetary or nonmonetary, can alleviate customers’ negative emotions, while providing compensation for future travel does not have any impact on emotions. Findings further suggest that positive employee attitudes, behaviors, and prompt service recovery actions generate more positive emotions while alleviating negative emotions compared to compensations provided. Service failures and timely, reliable, and satisfactory recovery actions have greater influences on travelers who fly with full-service airlines and in business class compared with travelers who fly with low-cost airlines and in economy class. Customers’ emotions influence their satisfaction and recommendation likelihood.
Adipokine profile and urinary albumin excretion in isolated growth hormone deficiency.

BACKGROUND GH deficiency (GHD) is often associated with cardiovascular risk factors, including abdominal fat accumulation, hypercholesterolemia, and increased C-reactive protein. Despite the presence of these risk factors, adults with congenital lifetime isolated GHD (IGHD) due to an inactivating mutation in the GHRH receptor gene do not have premature atherosclerosis. OBJECTIVE The aim was to study the serum levels of adiponectin and leptin (antiatherogenic and atherogenic adipokine, respectively), and the urinary albumin excretion (UAE) in these IGHD individuals. DESIGN AND PATIENTS We conducted a cross-sectional study of 20 IGHD individuals (seven males; age, 50.8 +/- 14.6 yr) and 22 control subjects (eight males; age, 49.9 +/- 11.5 yr). MAIN OUTCOME MEASURES Anthropometric factors, body composition, blood pressure, serum adiponectin, leptin, and UAE were measured. RESULTS Adiponectin was higher [12.8 (7.1) vs. 9.7 (5) ng/ml; P = 0.041] in IGHD subjects, whereas no difference was observed in leptin [7.3 (6.3) vs. 9.3 (18.7 ng/ml] and UAE [8.6 (13.8) vs. 8.5 (11.1) microg/min]. CONCLUSIONS Subjects with lifetime untreated IGHD have an adipokine profile with high adiponectin and normal leptin levels that may delay vascular damage and lesions of the renal endothelium.
Conversing about Citrus Greening: Extension's Role in Educating about Genetic Modification Science as a Solution.

Extension agents across the nation will need to facilitate difficult conversations with the public if genetic modification (GM) science is used to combat citrus greening disease. This study used the innovation characteristics described by Rogers to explore if using GM science as a solution to citrus greening had diffused amongst US residents. An online survey was completed by 1,051 respondents across the US. Respondents were then classified into geographic regions. Demographic differences amongst respondents from the regions were identified; however, respondents from all regions had neutral perceptions of GM science’s compatibility, trialability, complexity, and observability. All regions aside from the West agreed there was a relative advantage to using GM science; the West neither agreed nor disagreed. The Midwest was the only region with half of respondents agreeing they would consume GM citrus. All diffusion characteristics aside from observability were predictors of GM citrus consumption, and when accounting for diffusion characteristics, the Midwest was less likely to consume GM products when compared to the Northeast. Recommendations are offered for how extension agents can develop educational programming tailored to the needs of their regions to aid consumers in making educated decisions about GM citrus in the future.
Compliance with hepatitis B vaccination in 1175 heroin users and risk factors associated with lack of vaccine response.

AIMS To investigate the feasibility of hepatitis B vaccination among heroin users, assessing adherence to the vaccination schedules and identifying factors associated with antibody response. DESIGN AND PARTICIPANTS A large cohort study in nine public centres for drug users (PCDUs) in north-eastern Italy, with data collected between January 1989 and December 1998. A total of 1175 heroin users were selected and vaccinated with a recombinant vaccine using two schedules (0-1-6 months and 0-1-2 months). FINDINGS Eighty-eight per cent of patients completed the vaccination series and a protective antibody response occurred in 77% of subjects. Completion of the vaccination series was not related to the length of the vaccination schedule or whether the patient was still in drug abuse treatment at the end of the series, but was related strongly to the number of patients enrolled at each PCDU (Spearman correlation = - 0.93, P < 0.001). Four variables were significantly associated with lack of seroconversion in response to vaccination: older age (AOR = 0.91 per year, 95% CI 0.88-0.94, P < 0.001), 2-month vaccination schedule (AOR = 3.10, 95% CI 2.06-4.68, P < 0.001), HCV seropositivity (AOR = 0.69, 95% CI 0.47-0.99, P = 0.04), HIV seropositivity (AOR = 0.27, 95% CI 0.10-0.77, P = 0.01). CONCLUSIONS A large-scale, multi-site hepatitis B vaccination programme for heroin users proved feasible and effective. The factors associated with a lack of antibody response may be useful in identifying patients who would benefit most from routine post-vaccination testing, with booster doses for non-responders. These results suggest that hepatitis B vaccination for drug users should become a routine public health practice.