Miracle-dz/UniFAR-FTUs huggingface dataset:
Dronedarone: an emerging therapy for atrial fibrillation

Atrial fibrillation (AF) is a common arrhythmia, with a prevalence ranging from 0.1% to 9.0% at different ages, and is associated with increased cardiovascular events and mortality. A significant increase in the prevalence of the disease is expected to occur in the coming years as a consequence of the aging of the population and advances in the management of coronary artery disease and heart failure. Effective rhythm control may be difficult to obtain in a significant proportion of patients with AF. The limited efficacy and the possible adverse effects of antiarrhythmic drugs has led researchers to focus their attention on new molecules, in a search of compounds with antiarrhythmic efficacy and a more favourable safety profile. Among several new drugs developed for the management of AF, dronedarone, a benzofuran derivative that shares many of the antiarrhythmic properties of amiodarone, but with a more favourable safety profile, seems particularly promising. The drug is noniodinated, has less lipophilicity, reaches therapeutic concentrations over a shorter period of time and has lower tissue accumulation. Dronedarone, similarly to amiodarone, exhibits electrophysiologic characteristics of all 4 Vaughan Williams classes. Clinical studies have shown that dronedarone effectively reduces ventricular rate, may prevent or delay the recurrence of AF, and may reduce cardiovascular morbidity and mortality in patients with AF or atrial flutter. The drug has an overall good safety profile, in particular with low pulmonary and thyroid toxicity. An important exception is represented by patients with unstable haemodynamic conditions, in which the use of dronedarone has been found to be associated with an increase in mortality. Dronedarone has been recently approved for clinical use by the Food and Drug Administration and by the European Medicines Agency. Further results from trials and clinical use will better define the efficacy and safety profile of dronedarone in AF compared with other antiarrhythmic drugs and its role in the management of patients with AF.
CD4+ beta islet cell-reactive T cell clones that suppress autoimmune diabetes in nonobese diabetic mice

We report the isolation of a panel of CD4+ T helper type 1 autoreactive T cell clones from the spleen of unprimed nonobese diabetic mice, a murine model of human insulin-dependent diabetes mellitus. The T cell clones express a diverse repertoire of T cell receptors, three of which recognize beta islet cell autoantigen(s). The islet cell-reactive T cell clones inhibit adoptive transfer of insulin-dependent diabetes mellitus and intraislet lymphocytic infiltration. The protective capacity of the T cell clones correlates with their ability to produce a novel immunoregulatory activity that potently inhibits in vitro allogeneic mixed lymphocyte reaction. The partially purified activity significantly inhibited the adoptive transfer of diabetes. Our work provides evidence in support of the existence of T helper type 1, CD4+ T cells reactive to beta islet cell autoantigens that have acquired a protective instead of a diabetogenic effector function. These T cells mediate their protective action in part by production of an immunoregulatory activity capable of down-regulating immune responses, and they are likely to represent a population of regulatory T cells that normally plays a role in maintaining peripheral tolerance.
The testing effect: The role of feedback and collaboration in a tertiary classroom setting

SUMMARY Successful retrieval on a test compared to just re-studying material improves long-term retention—a phenomenon called the ‘testing effect’. This study investigated the role of feedback and collaborative testing on the retention of course material in a tertiary educational setting. Tested material was better retained relative to non-tested material (testing effect), and feedback facilitated correction of errors. Group testing produced higher performance on the initial, but not final test performance, compared to individual testing. This set of findings suggests that to encourage long-term retention, educators should utilise individual formative testing with feedback; theoretical implications are also discussed. Copyright # 2009 John Wiley & Sons, Ltd. The core purpose of education and training is the transfer of knowledge to students, such that this knowledge is retained in the long-term. Research has suggested that testing is one way to increase long-term retention, relative to re-studying material or not being tested (Glover, 1989; Spitzer, 1939). This phenomenon is called the ‘testing effect’. One prominent theoretical explanation singles out the key role played by retrieval effort in accounting for the testing effect. Internal memorial processes, like retrieval, are proposed to be the direct effect of the testing procedure on memory, in contrast to indirect effects such as motivation for subsequent study (see Roediger & Karpicke, 2006a, for a review). Most of the research on the testing effect has been conducted in the laboratory. Formative testing with feedback, as well as group activities, is becoming more common in educational settings; however the effectiveness of these strategies, particularly in combination, has received little evaluative attention. The current study examines these issues in a tertiary educational context.
Transcription of follicle-stimulating hormone subunit genes is modulated by porcine LIM homeobox transcription factors, LHX2 and LHX3

Brassica rapa is a polyploid species with phenotypically diverse cultivated subspecies. Glucosinolates (GSLs) are secondary metabolites that contribute to anticarcinogenic activity and plant defense in Brassicaceae. Previously, complete coding sequences of 13 BrMYB transcription factors (TFs) related to GSL biosynthesis were identified in the B. rapa genome. In the present study, we investigated GSL content and expression levels of these BrMYB TFs in 38 accessions belonging to eight subspecies of B. rapa. Twelve identified GSLs were detected and were classified into three chemical groups based on patterns of GSL content and expression profiles of the BrMYB TFs. GSL content and BrMYB TF expression levels differed among genotypes, including B. rapa subspecies pekinensis, chinensis and rapa. BrMYB28.3, BrMYB51.1 and BrMYB122.2 positively regulated GSL content in 38 accessions. Furthermore, expression levels of BrMYB28s and BrMYB34.3 increased under most abiotic and biotic stress treatments. The three BrMYB51 paralogs also showed drastically increased expression levels after infection with Pectobacterium carotovorum. The results of the present study improve our understanding of the functional diversity of these 13 BrMYB TFs during the evolution of polyploid B. rapa.
Attitudes towards e-learning amongst dental students at the universities in Croatia.

AIM To develop and test the psychometric characteristics of a questionnaire that measures attitudes towards e-learning, as well as to study attitudes about e-learning and to identify variables related to those attitudes amongst dental students. SUBJECT AND METHODS The study was conducted from November 2010 to December 2011 at all three Croatian dental schools. A questionnaire entitled 'Attitude Towards e-Learning' consisting of 12 questions about socio-demographic data and 22 statements about attitude towards e-learning was self-administered by 386 students. Factorial analysis and Cronbach's alpha were used to test the psychometric characteristics of the questionnaire. Multiple regression analysis was used to identify variables related to attitudes towards e-learning. RESULTS Factorial analysis confirmed two factors: positive attitude and negative attitude, which interpret 58% of the total variance and had good internal consistency of α = 0.852 and 0.668, respectively. The average score of positive attitude was 42 ± 6, indicating a highly positive attitude towards e-learning. The average score of negative attitude was 27 ± 6, indicating minor negative attitude. Higher age and study year, usage of the Internet in education, more frequent usage of Facebook and more attendance of e-courses demonstrated a significant influence on positive attitude towards e-learning (R(2) = 0.304; P < 0.001). Lower year of study and less frequent attendance of e-courses had a significant influence on negative attitude (R(2) = 0.268; P < 0.001). CONCLUSIONS Dental students have generally positive attitudes towards e-learning. Teachers should adopt strategies to change negative attitudes by introducing more e-learning courses in lower study years and should encourage students to use the Internet in their education and communication with teachers and colleagues.
Transient NN random walk on the line

We prove strong theorems for the local time at infinity of a nearest neighbor transient random walk. First, laws of the iterated logarithm are given for the large values of the local time. Then we investigate the length of intervals over which the walk runs through (always from left to right) without ever returning.
Implementing hospital-based surveillance for severe acute respiratory infections caused by influenza and other respiratory pathogens in New Zealand.

BACKGROUND Recent experience with pandemic influenza A(H1N1)pdm09 highlighted the importance of global surveillance for severe respiratory disease to support pandemic preparedness and seasonal influenza control. Improved surveillance in the southern hemisphere is needed to provide critical data on influenza epidemiology, disease burden, circulating strains and effectiveness of influenza prevention and control measures. Hospital-based surveillance for severe acute respiratory infection (SARI) cases was established in New Zealand on 30 April 2012. The aims were to measure incidence, prevalence, risk factors, clinical spectrum and outcomes for SARI and associated influenza and other respiratory pathogen cases as well as to understand influenza contribution to patients not meeting SARI case definition. METHODS/DESIGN All inpatients with suspected respiratory infections who were admitted overnight to the study hospitals were screened daily. If a patient met the World Health Organization's SARI case definition, a respiratory specimen was tested for influenza and other respiratory pathogens. A case report form captured demographics, history of presenting illness, co-morbidities, disease course and outcome and risk factors. These data were supplemented from electronic clinical records and other linked data sources. DISCUSSION Hospital-based SARI surveillance has been implemented and is fully functioning in New Zealand. Active, prospective, continuous, hospital-based SARI surveillance is useful in supporting pandemic preparedness for emerging influenza A(H7N9) virus infections and seasonal influenza prevention and control.
The Impact of Diet and Lifestyle on Gut Microbiota and Human Health

There is growing recognition of the role of diet and other environmental factors in modulating the composition and metabolic activity of the human gut microbiota, which in turn can impact health. This narrative review explores the relevant contemporary scientific literature to provide a general perspective of this broad area. Molecular technologies have greatly advanced our understanding of the complexity and diversity of the gut microbial communities within and between individuals. Diet, particularly macronutrients, has a major role in shaping the composition and activity of these complex populations. Despite the body of knowledge that exists on the effects of carbohydrates there are still many unanswered questions. The impacts of dietary fats and protein on the gut microbiota are less well defined. Both short- and long-term dietary change can influence the microbial profiles, and infant nutrition may have life-long consequences through microbial modulation of the immune system. The impact of environmental factors, including aspects of lifestyle, on the microbiota is particularly poorly understood but some of these factors are described. We also discuss the use and potential benefits of prebiotics and probiotics to modify microbial populations. A description of some areas that should be addressed in future research is also presented.
Acute hepatitis B in blood donors over a 5‐year period in England and North Wales: who is getting infected?

Hepatitis B virus (HBV) remains the infection most frequently recognized by donation testing in blood donors. It is usually a persistent infection and mostly reflects the country of origin of the donor or the donor's family. There are, however, a minority of acute infections and this study undertook their phylogenetic analysis to determine the likely source of infection.
Children's Social Welfare in China, 1989–1997: Access to Health Insurance and Education

Fundamental changes in China's finance system for social services have decentralized responsibilities for provision to lower levels of government and increased costs to individuals. The more localized, market-oriented approaches to social service provision, together with rising economic inequalities, raise questions about access to social services among China's children. With a multivariate analysis of three waves of the China Health and Nutrition Survey (1989, 1993 and 1997), this article investigates two dimensions of children's social welfare: health care, operationalized as access to health insurance, and education, operationalized as enrolment in and progress through school. Three main results emerge. First, analyses do not suggest an across-the-board decline in access to these child welfare services during the period under consideration. Overall, insurance rates, enrolment rates and grade-for-age attainment improved. Secondly, while results underscore the considerable disadvantages in insurance and education experienced by poorer children in each wave of the survey, there is no evidence that household socio-economic disparities systematically widened. Finally, findings suggest that community resources conditioned the provision of social services, and that dimensions of community level of development and capacity to finance public welfare increasingly mattered for some social services.
Variable Electrospray Ionization and Matrix-Assisted Laser Desorption/Ionization Mass Spectra of the Bisquaternary Ammonium Salt Ethonium

Determination of a single “fingerprint” mass spectrum of a biologically active compound, required for compound identification in mixtures and biological materials in such applied tasks as ecological monitoring and biological imaging, may become a nontrivial problem for labile compounds whose mass spectra depend strongly on the applied experimental conditions. In the present communication, qualitatively different mass spectral patterns obtained for the bisquaternary ammonium salt ethonium Cat2+•2Cl– under varied conditions of electrospray ionization and matrixassisted laser desorption/ionization (MALDI) are described and systematized. It is shown that qualitative changes in the electrospray mass spectra of ethonium occur upon a cone voltage increase from 10 V to 100 V, which are caused by the subsequent appearance and destruction of several primary ions: the intact dication Cat2+, the dication-counterion cluster Cat2+•Cl– and[Cat âÂ€Â‘ H]+ and [Cat âÂ€Â‘ CH3]+ ions. Novel experimental evidence of survival of the gas-phase dication Cat2+ with the shortest possible distance of ca 4 Co between the quaternary nitrogen atoms provided by two CH2 groups and Cat2+ fragmentation with preservation of the doubly charged state of the fragments are revealed under soft electrospray conditions. The interpretation of the MALDI mass spectrum is made taking into account the formation of a salt of the bisquaternary ammonium base and 2,5-dihydroxybenzoic acid, which results in the absence of any chlorine-containing ions in the mass spectra and a fragment ion distribution that is different from that observed under electrospray ionization conditions. The main mass spectral features revealed for ethonium may aid in the identification of other types of bisquaternary ammonium compounds.
Can the blood pressure predict cognitive task performance in a healthy population sample?

Objectives To study the relation between the blood pressure and the neurocognitive function within the full adult age range in a large population sample. Design A cross-sectional study of 936 healthy adults who were recruited from a register of family practices, stratified for age (24–81 years), sex, and occupational level, who took part in a medical and neurocognitive test program. Methods The blood pressure status was studied in relation to five measures of cognitive ability, including verbal memory and speed of information processing. Other vascular risk factors were treated as control variables and included smoking, alcohol intake, body mass index, and body fat distribution. The blood pressure was measured five times using an automatic recording technique (with a Dinamap 8100 device). Results After adjustment for age, sex, and educational level in a hierarchical regression analysis, we found no unequivocal association between the mean systolic and diastolic blood pressures (or any other studied vascular risk factor) and cognitive test performance both for the whole group and for the subgroup of subjects who were not being administered antihypertensive medication and whose medical history did not include cardiovascular events. Stratified analysis within four age levels revealed no age-specific associations between the blood pressure and the cognitive function. Subjects whose blood pressure was within the hypertensive range performed worse than did matched controls at letter digit copying, but not according to other cognitive measures. Conclusions With a population-based sample unselected for blood pressure status we found no linear relationship between the actual blood pressure level and various aspects of cognitive performance. Prospective studies are needed to investigate the possibility that the systemic blood pressure load over time is associated with a decline in specific cognitive abilities.
De novo Alu element insertions targeted to a sequence common to the BRCA1 and BRCA2 genes

Linkage analysis suggests that mutations in the BRCA1 and BRCA2 genes are responsible for cancer predisposition in more than 80% of the families with high incidence of breast/ovarian cancer. However, pathogenic mutations in the BRCA1/2 genes are generally identified in much less than half of the families investigated in a diagnostic setting with the currently used PCR‐based screening protocols. Here we report the identification of two different de novo Alu element insertions within the BRCA1/2 coding sequences in three out of the 50 families in which we found a cancer predisposing mutation, suggesting that this type of mutation is much more common than suggested by their occurrence in mutation databases. The Alu insertion in the BRCA2 gene resulted in the removal of the targeted exon from the corresponding mRNA molecule. Unexpectedly the Target Site Duplications generated by both Alu element insertions contained a specific 9 bp long segment, which might eventually serve as a recognition site for the transposition machinery. Finally, in contrast to the disease causing Alu insertions reported to date, the transposon identified in the BRCA1 gene does not belong to a “young” AluY but to an AluS subfamily, indicating that some of these “old” Alu elements, which are supposed to be non‐functional fossil relics, are still able to retrotranspose in vivo. © 2005 Wiley‐Liss, Inc.
Isotopic overprinting of nitrification on denitrification as a ubiquitous and unifying feature of environmental nitrogen cycling

Significance Stable isotopes of nitrate have long provided a tool for tracking environmental sources and biological transformations. However, divergent interpretations of fundamental nitrate isotope systematics exist among disciplinary divisions. In an effort to transcend disciplinary boundaries of terrestrial and marine biogeochemistry, we use a quantitative model for coupled nitrogen and oxygen isotopes of nitrate founded on benchmarks established from microbial cultures, to reconcile decades of nitrate isotopic measurements in freshwater and seawater and move toward a unified understanding of cycling processes and isotope systematics. Our findings indicate that denitrification operates within the pervasive context of nitrite reoxidation mechanisms, specifically highlighting the relative importance of nitrification in marine denitrifying systems and anammox in groundwater aquifers. Natural abundance nitrogen and oxygen isotopes of nitrate (δ15NNO3 and δ18ONO3) provide an important tool for evaluating sources and transformations of natural and contaminant nitrate (NO3−) in the environment. Nevertheless, conventional interpretations of NO3− isotope distributions appear at odds with patterns emerging from studies of nitrifying and denitrifying bacterial cultures. To resolve this conundrum, we present results from a numerical model of NO3− isotope dynamics, demonstrating that deviations in δ18ONO3 vs. δ15NNO3 from a trajectory of 1 expected for denitrification are explained by isotopic over-printing from coincident NO3− production by nitrification and/or anammox. The analysis highlights two driving parameters: (i) the δ18O of ambient water and (ii) the relative flux of NO3− production under net denitrifying conditions, whether catalyzed aerobically or anaerobically. In agreement with existing analyses, dual isotopic trajectories >1, characteristic of marine denitrifying systems, arise predominantly under elevated rates of NO2− reoxidation relative to NO3− reduction (>50%) and in association with the elevated δ18O of seawater. This result specifically implicates aerobic nitrification as the dominant NO3− producing term in marine denitrifying systems, as stoichiometric constraints indicate anammox-based NO3− production cannot account for trajectories >1. In contrast, trajectories <1 comprise the majority of model solutions, with those representative of aquifer conditions requiring lower NO2− reoxidation fluxes (<15%) and the influence of the lower δ18O of freshwater. Accordingly, we suggest that widely observed δ18ONO3 vs. δ15NNO3 trends in freshwater systems (<1) must result from concurrent NO3− production by anammox in anoxic aquifers, a process that has been largely overlooked.
Melanocortins defend their territory: multifaceted neuroprotection in cerebral ischemia.

Stroke is the leading cause of adult disability and the third leading cause of death (1). Its dramatic, often catastrophic attack unleashes an extremely challenging therapeutic target. Typically, an intravascular blood clot occludes a vessel such as the middle cerebral artery, causing focal ischemia deep in its perfusion territory, and triggering a rapidly closing window of opportunity for treatment before neurological damage becomes irreversible. The sole approved therapy is to attempt reperfusion using thrombolytic agents within 3 h of symptom onset, but most patients are excluded by this requirement or by other eligibility criteria, and the treatment exposes patients to significant risk of intracerebral hemorrhage. Only a fraction of treated patients experience some benefit (2, 3). Consequently, a major goal of stroke research is to develop interventions that are effective and safe after longer treatment delays. Against this backdrop, in this issue Giuliani et al. (4) report promising findings of pharmacological neuroprotection in cerebral ischemia by a synthetic melanocortin (ACTH/MSH-related peptide).