Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunogenicity and Protective Capacity of a Virosomal Respiratory Syncytial Virus Vaccine Adjuvanted with Monophosphoryl Lipid A in Mice

Respiratory Syncytial Virus (RSV) is a major cause of viral brochiolitis in infants and young children and is also a significant problem in elderly and immuno-compromised adults. To date there is no efficacious and safe RSV vaccine, partially because of the outcome of a clinical trial in the 1960s with a formalin-inactivated RSV vaccine (FI-RSV). This vaccine caused enhanced respiratory disease upon exposure to the live virus, leading to increased morbidity and the death of two children. Subsequent analyses of this incident showed that FI-RSV induces a Th2-skewed immune response together with poorly neutralizing antibodies. As a new approach, we used reconstituted RSV viral envelopes, i.e. virosomes, with incorporated monophosphoryl lipid A (MPLA) adjuvant to enhance immunogenicity and to skew the immune response towards a Th1 phenotype. Incorporation of MPLA stimulated the overall immunogenicity of the virosomes compared to non-adjuvanted virosomes in mice. Intramuscular administration of the vaccine led to the induction of RSV-specific IgG2a levels similar to those induced by inoculation of the animals with live RSV. These antibodies were able to neutralize RSV in vitro. Furthermore, MPLA-adjuvanted RSV virosomes induced high amounts of IFNγ and low amounts of IL5 in both spleens and lungs of immunized and subsequently challenged animals, compared to levels of these cytokines in animals vaccinated with FI-RSV, indicating a Th1-skewed response. Mice vaccinated with RSV-MPLA virosomes were protected from live RSV challenge, clearing the inoculated virus without showing signs of lung pathology. Taken together, these data demonstrate that RSV-MPLA virosomes represent a safe and efficacious vaccine candidate which warrants further evaluation.
Increasing prevalence of genital herpes in developing countries: implications for heterosexual HIV transmission and STI control programmes.

BACKGROUND The recognition that sexually transmitted infections (STI) facilitate HIV transmission among heterosexuals has led to a rejuvenated focus on improving STI control as a component of HIV prevention programmes in developing countries. While efforts so far have focused mainly on all STI, there is increasing evidence that genital ulcers facilitate a considerable proportion of HIV transmission among heterosexuals and that this effect has been underestimated. This paper focuses on the epidemiology of genital herpes in developing countries past and present. OBJECTIVES To review the scientific literature about the epidemiology of genital herpes in developing countries and discuss the implications of the findings for STI control and HIV prevention programmes. SEARCH METHODOLOGY: A Medline search for June 1966 to August 1999 using the keywords, genital herpes, STD and developing countries, and genital ulcers in MeSH and free text. Abstract books from recent international AIDS conferences and other international STD conferences were reviewed. The annual reports of the medical officers of heath for Harare 1982-1998 and Durban 1989-1997 were reviewed to detect trends in genital herpes diagnoses. FINDINGS Genital herpes, formerly regarded as a minor STI in most developing countries, has now emerged as a leading cause of genital ulceration in many countries where syphilis and chancroid were more prevalent previously. This increased recognition of genital herpes reflects both a change in the pattern of STI epidemiology through a decline in syphilis and chancroid as a response to HIV control programmes and improved techniques for diagnosing herpetic infection. Countries with significant heterosexual HIV epidemics also appear to have rapidly increasing numbers of genital herpes cases. CONCLUSIONS The emergence of this herpes epidemic must be addressed through innovative strategies that will be viable, sustainable, acceptable, and effective in developing countries. In countries where genital herpes is a significant problem, local adaptation of WHO treatment algorithms should be made. STI service providers should be trained about issues around the transmission of herpes and how best to advise clients about dealing with, and recognising, recurrences. The effectiveness of antiviral treatment for genital herpes should be investigated in core groups at high risk of HIV.
Predictors of crop diversification: a survey of tobacco farmers in North Carolina (USA)

OBJECTIVE To assess the attitudes and behaviours of North Carolina tobacco farmers around crop diversification. DESIGN Cross-sectional telephone survey. PARTICIPANTS Active tobacco farmers in 14 North Carolina counties (n = 1236), interviewed between January and April 1997 (91% response rate). OUTCOME MEASURES Interest in, experience with, and perceived barriers to diversification. RESULTS Most farmers (95%) grew/raised a commodity other than tobacco (mean = 2.8). A total of 60% of farmers expressed interest in trying other on-farm activities to supplement their tobacco and 60% reported taking action in the past year around supplementation. Younger age and college education were positively associated with interest. College education, off-farm income, and larger farm size were associated with the number of actions taken. For perceived external barriers to diversification, use of tobacco, percent income from tobacco, lack of college education, and younger age were most strongly associated with the number of barriers. For internal barriers (personal factors), percent income from tobacco, use of tobacco, and lack of college education were most strongly associated with the number of barriers. CONCLUSIONS Most farmers were involved in diverse operations and expressed interest in continuing to diversify, although the breadth of diversification was narrow. Farmers noted many barriers to diversifying. If conventional production and marketing techniques are employed for non-tobacco alternatives, these alternatives may not provide the sustainable profitability that tobacco has afforded. Competition from foreign tobacco growers is the primary threat to the future of American growers and tobacco dependent communities.
Efficacy of lipid lowering drug treatment for diabetic and non-diabetic patients: metaanalysis of randomised controlled trials

Abstract Objective To evaluate the clinical benefit of lipid lowering drug treatment in patients with and without diabetes mellitus, for primary and secondary prevention. Design Systematic review and meta-analysis. Data sources Cochrane, Medline, Embase, and reference lists up to April 2004. Study selection Randomised, placebo controlled, double blind trials with a follow-up of at least three years that evaluated lipid lowering drug treatment in patients with and without diabetes mellitus. Data extraction Two independent reviewers extracted data. The primary outcome was major coronary events defined as coronary heart disease death, non-fatal myocardial infarction, or myocardial revascularisation procedures. Results Twelve studies were included. Lipid lowering drug treatment was found to be at least as effective in diabetic patients as in non-diabetic patients. In primary prevention, the risk reduction for major coronary events was 21% (95% confidence interval 11% to 30%; P < 0.0001) in diabetic patients and 23% (12% to 33%; P = 0.0003) in non-diabetic patients. In secondary prevention, the corresponding risk reductions were 21% (10% to 31%; P = 0.0005) and 23% (19% to 26%; P ≤ 0.00001). However, the absolute risk difference was three times higher in secondary prevention. When results were adjusted for baseline risk, diabetic patients benefited more in both primary and secondary prevention. Blood lipids were reduced to a similar degree in both groups. Conclusions The evidence that lipid lowering drug treatment (especially statins) significantly reduce cardiovascular risk in diabetic and non-diabetic patients is strong and suggests that diabetic patients benefit more, in both primary and secondary prevention. Future research should define the threshold for treatment of these patients and the desired target lipid concentrations, especially for primary prevention.
Accumulation of Very-Long-Chain Fatty Acids in Membrane Glycerolipids Is Associated with Dramatic Alterations in Plant Morphology

Transgenic Arabidopsis plants overexpressing the Arabidopsis FATTY ACID ELONGATION1 gene under the control of the 35S promoter from cauliflower mosaic virus accumulated very-long-chain fatty acids (VLCFAs) throughout the plant. In some transformants, C20 and C22 VLCFAs accounted for >30% of the total fatty acids, accumulating at the expense of C16 and C18 fatty acids. These C20 and C22 fatty acids were incorporated into all of the major membrane glycerolipid classes. Plants with a high VLCFA content displayed a dramatically altered morphology, which included the failure of flowering shoots to elongate, a modified spatial pattern of siliques, an altered floral phenotype, and a large accumulation of anthocyanins. In addition, these plants also exhibited a unique alteration of the chloroplast membrane structure. We discuss a possible role for VLCFAs in establishing the shape/curvature of the membranes, which in turn may affect the shape of the cell and ultimately that of the whole plant.
Soft gamma repeaters and anomalous X-ray pulsars: magnetar candidates

Introduction Baade and Zwicky (1934) were the first to envision the formation of neutron stars as the end product of a supernova explosion. Their forward thinking was not vindicated for another three decades, with the discovery of the first radio pulsars by Bell and Hewish (Hewish et al. 1968). What Baade and Zwiscky could not have anticipated, however, was the menagerie of astrophysical objects that are now associated with neutron stars. Today, we observe them as magnetically braking pulsars, accreting pulsars in binary systems, isolated cooling blackbodies, sources of astrophysical jets, and emitters of high-luminosity bursts of X-rays. Here, we focus on two of the most extraordinary evolutionary paths of a neutron star, namely soft gamma repeaters (SGRs) and anomalous X-ray pulsars (AXPs). Soft gamma repeaters were discovered as high-energy transient burst sources; some were later found also to be persistent X-ray pulsars, with periods of several seconds, that are spinning down rapidly. Anomalous X-ray pulsars are identified through their persistent pulsations and rapid spin down; some have also been found to emit SGR-like bursts. In spite of the differing methods of discovery, this convergence in the observed properties of the SGRs and AXPs has made it clear that they are, fundamentally, the same type of object. What distinguishes them from other neutron stars is the likely source of energy for their radiative emissions, magnetism.
Midwives’ perceptions and experiences of health promotion practice in Ghana

Introduction: This research explores midwives’ perceptions and experiences of health promotion practice in Ghana. Methods: A qualitative descriptive exploratory design was used in order to gain better insight into midwives’ perceptions and experiences of health promotion practice. A total of 21 midwives took part in the study. Data were collected by individual in-depth semi-structured interviews. Thematic analysis was used to analyse the transcript. Results: Five dominant themes emerged from the interview transcripts, namely: health promotion as education, health promotion activities, the value of health promotion, client participation, and midwives’ barriers to promoting health. Although midwives underscored the importance of health promotion to their work, their reports indicated that, in practice, midwives mostly delivered health education and behaviour change communication rather than health promotion. The midwives expressed the view that by way of their close association with women, they were in a better position to influence women’s health. Health promotion activities engaged by the midwives included weight management, healthy eating, infection prevention, personal hygiene, counselling on family planning, and screening for hazardous and harmful substance use such as alcohol and smoking. All the midwives mentioned that clients participated in their health promotion activities. Factors that were identified by the midwives to enhance client participation were trust, attitude of the midwife, building rapport, creating enabling environment, listening and paying attention to clients and using simple language. The barriers to health promotion identified by the midwives included time, stress, culture, lack of training and inadequate health educational materials. Discussion: Midwives in this study had limited knowledge about health promotion, yet could play a significant role in influencing health; thus there is a need for on-going in-service training for midwives to focus on health promotion.
What Drives False Memories in Psychopathology? A Case for Associative Activation

In clinical and court settings, it is imperative to know whether posttraumatic stress disorder (PTSD) and depression may make people susceptible to false memories. We conducted a review of the literature on false memory effects in participants with PTSD, a history of trauma, or depression. When emotional associative material was presented to these groups, their levels of false memory were raised relative to those in relevant comparison groups. This difference did not consistently emerge when neutral or nonassociative material was presented. Our conclusion is supported by a quantitative comparison of effect sizes between studies using emotional associative or neutral, nonassociative material. Our review suggests that individuals with PTSD, a history of trauma, or depression are at risk for producing false memories when they are exposed to information that is related to their knowledge base.
The Impact of Vision Impairment Questionnaire: an evaluation of its measurement properties using Rasch analysis.

PURPOSE To explore the psychometric properties of the Impact of Vision Impairment scale (IVI) by using Rasch analysis. METHODS Three hundred fourteen first-time referrals to low-vision clinics completed the 32-item IVI. The data were Rasch-analyzed with a partial credit model using RUMM2020 software (RUMM Laboratory, Perth, WA, Australia). The overall fit of the model, response scale, individual item fit, differential item functioning, unidimensionality, and person-separation reliability were assessed. RESULTS Initially, 26 items displayed disordered thresholds. However, collapsing the response scale to three categories (4 items) and four categories (28 items) produced ordered response thresholds for all items. Four items with high proportions of missing responses, poor spread, high skewness, and deviation between observed and expected model curves were then removed. This adjustment produced overall fit to the Rasch model (item-trait interaction chi(2) = 118.3; P = 0.32). The final mean (SD) person and item fit residuals ere 0.06 (0.85) and -0.20 (1.45), respectively. The person-separation reliability was 0.9, indicating that the scale was able to discriminate between several different groups of participants. The revised scale was well targeted to the participants, with similar mean locations for items (0.00) and persons (0.16). A significant difference between participants of mild, moderate, and severe visual impairment (ANOVA; P 0.001) supported the criterion validity of the Rasch-scaled IVI. CONCLUSIONS The results provide support for the measurement properties of the Rasch-scaled 28-item version of the IVI and of its potential for assessing outcomes of low-vision rehabilitation. A raw score-to-Rasch person measure conversion is supplied.
Outcomes of Extremely Preterm Infants Born to Insulin-Dependent Diabetic Mothers

BACKGROUND AND OBJECTIVE: Little is known about in-hospital morbidities and neurodevelopmental outcomes among extremely preterm infants born to women with insulin-dependent diabetes mellitus (IDDM). We examined risks of mortality, in-hospital morbidities, and neurodevelopmental outcomes at 18 to 22 months’ corrected age between extremely preterm infants of women with insulin use before pregnancy (IBP), with insulin use started during pregnancy (IDP), and without IDDM. METHODS: Infants 22 to 28 weeks’ gestation born or cared for at a Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network center (2006–2011) were studied. Regression models compared the association between maternal IDDM and timing of insulin use and the outcomes of the 3 groups. RESULTS: Of 10 781 infants, 536 (5%) were born to women with IDDM; 58% had IBP, and 36% had IDP. Infants of mothers with IBP had higher risks of necrotizing enterocolitis (adjusted relative risk [RR] = 1.55 [95% confidence interval (CI) 1.17–2.05]) and late-onset sepsis (adjusted RR = 1.26 [95% CI 1.07–1.48]) than infants of mothers without IDDM. There was some indication of higher in-hospital mortality risk among infants of mothers with IBP compared with those with IDP (adjusted RR = 1.33 [95% CI 1.00–1.79]). Among survivors evaluated at 18 to 22 months’ corrected age, average head circumference z score was lower for infants of mothers with IBP compared with those without IDDM, but there were no differences in risk of neurodevelopmental impairment. CONCLUSIONS: In this cohort of extremely preterm infants, infants of mothers with IBP had higher risks of necrotizing enterocolitis, sepsis, and small head circumference.
A Low-Computational-Complexity Algorithm for Hyperspectral Endmember Extraction: Modified Vertex Component Analysis

Endmember extraction represents one of the most challenging aspects of hyperspectral image processing. In this letter, a new algorithm for endmember extraction, named modified vertex component analysis (MVCA), is presented. This new technique outperforms the popular vertex component analysis (VCA) by applying a low-complexity orthogonalization method and by utilizing integer instead of floating-point arithmetic when dealing with hyperspectral data. The feasibility of this technique is demonstrated by comparing its performance with VCA on synthetic mixtures as well as on the well-known Cuprite hyperspectral image. MVCA shows promising results in terms of much lower computational complexity, still reproducing similar endmember accuracy than its original counterpart. Moreover, the features of this algorithm combined with state-of-the-art hardware implementations qualify MVCA as a good potential candidate for all those applications in which real time is a must.
Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis

Atherosclerotic lesions develop in regions of arterial curvature and branch points, which are exposed to disturbed blood flow and have unique gene expression patterns. The cellular and molecular basis for atherosclerosis susceptibility in these regions is not completely understood. In the intima of atherosclerosis-predisposed regions of the wild-type C57BL/6 mouse aorta, we quantified increased expression of several proinflammatory genes that have been implicated in atherogenesis, including vascular cell adhesion molecule–1 (VCAM-1) and a relative abundance of dendritic cells, but only occasional T cells. In contrast, very few intimal leukocytes were detected in regions resistant to atherosclerosis; however, abundant macrophages, including T cells, were found throughout the adventitia (Adv). Considerably lower numbers of intimal CD68+ leukocytes were found in inbred atherosclerosis-resistant C3H and BALB/c mouse strains relative to C57BL/6 and 129; however, leukocyte distribution throughout the Adv of all strains was similar. The predominant mechanism for the accumulation of intimal CD68+ cells was continued recruitment of bone marrow–derived blood monocytes, suggestive of low-grade chronic inflammation. Local proliferation of intimal leukocytes was low. Intimal CD68+ leukocytes were reduced in VCAM-1–deficient mice, suggesting that mechanisms of leukocyte accumulation in the intima of normal aorta are analogous to those in atherosclerosis.
Degenerate TCR recognition and dual DR2 restriction of autoreactive T cells: Implications for the initiation of the autoimmune response in multiple sclerosis

TCR degeneracy may facilitate self‐reactive T cell activation and the initiation of an autoimmune response in multiple sclerosis (MS). MHC class II alleles of the DR2 haplotype DR2a (DRB5*0101) and DR2b (DRB1*1501) are associated with an increased risk for MS in Caucasian populations. In order to selectively expand and characterize T cells with a high degree of TCR degeneracy that recognize peptides in the context of disease‐associated DR2 alleles, we developed DR2‐anchored peptide mixtures (APM). We report here that DR2‐APM have a high stimulatory potency and can selectively expand T cells with a degenerate TCR (TCRdeg). Due to the low concentration of individual peptides in the mixtures, T cell clones’ proliferative response to DR2‐APM implies that multiple peptides stimulate the TCR, which is a characteristic of TCRdeg. The frequency of DR2‐APM‐reactive T cells is significantly higher in MS patients than in healthy controls, suggesting that they may play a role in the development of the autoimmune response in MS. DR2‐APM‐reactive cells have a dual DR2 restriction: they recognize DR2‐APM in the context of both DR2a and DR2b molecules. The DR2‐APM‐reactive cells’ IL‐17 secretion, together with cross‐reactivity against myelin peptides, may contribute to their role in the development of autoimmune response in MS.
The Involvement of the Mid1/Cch1/Yvc1 Calcium Channels in Aspergillus fumigatus Virulence

Aspergillus fumigatus is a major opportunistic pathogen and allergen of mammals. Calcium homeostasis and signaling is essential for numerous biological processes and also influences A. fumigatus pathogenicity. The presented study characterized the function of the A. fumigatus homologues of three Saccharomyces cerevisiae calcium channels, voltage-gated Cch1, stretch-activated Mid1 and vacuolar Yvc1. The A. fumigatus calcium channels cchA, midA and yvcA were regulated at transcriptional level by increased calcium levels. The YvcA::GFP fusion protein localized to the vacuoles. Both ΔcchA and ΔmidA mutant strains showed reduced radial growth rate in nutrient-poor minimal media. Interestingly, this growth defect in the ΔcchA strain was rescued by the exogenous addition of CaCl2. The ΔcchA, ΔmidA, and ΔcchA ΔmidA strains were also sensitive to the oxidative stress inducer, paraquat. Restriction of external Ca2+ through the addition of the Ca2+-chelator EGTA impacted upon the growth of the ΔcchA and ΔmidA strains. All the A. fumigatus ΔcchA, ΔmidA, and ΔyvcA strains demonstrated attenuated virulence in a neutropenic murine model of invasive pulmonary aspergillosis. Infection with the parental strain resulted in a 100% mortality rate at 15 days post-infection, while the mortality rate of the ΔcchA, ΔmidA, and ΔyvcA strains after 15 days post-infection was only 25%. Collectively, this investigation strongly indicates that CchA, MidA, and YvcA play a role in A. fumigatus calcium homeostasis and virulence.