Miracle-dz/UniFAR-FTUs huggingface dataset:
Association Between Use of Long-Acting Nitrates and Outcomes in Heart Failure With Preserved Ejection Fraction

Background— Nitrates may be beneficial in heart failure with preserved ejection fraction (HFpEF) by enhancing cGMP signaling and improving hemodynamics, but real-world data on potential efficacy are lacking. Methods and Results— We linked the Swedish Heart Failure Registry to national registries with International Classification of Diseases, Tenth Revision comorbidity diagnoses and demographic and socioeconomic data. In HFpEF, defined as left ventricular ejection fraction ≥40%, we derived propensity scores for nitrate use using 52 baseline variables. The association between nitrate use and all-cause mortality and the composite of all-cause mortality or first heart failure hospitalization was assessed in a cohort matched 2:1 untreated to treated based on age and propensity score. In the overall HFpEF cohort (n=19 047; mean [SD] age, 76 [12] years; 46% women), nitrates were used in 17%, and the crude 1-year survival for treated versus untreated patients was 79% (95% confidence interval [CI], 78%–80%) versus 84% (95% CI, 83%–84%) respectively; hazard ratio was 1.48 (95% CI, 1.40–1.56; P<0.001) during a median 755-day follow-up. Matching yielded 2235 treated versus 4470 untreated patients, with 1-year survival of 80% (95% CI, 78%–82%) versus 79% (95% CI, 78%–81%) and hazard ratio of 1.06 (95% CI, 0.98–1.15; P=0.12). Nitrates were associated with worse composite outcome in the matched HFpEF cohort, with 1-year event-free survival of 62% (95% CI, 60%–64%) versus 65% (95% CI, 63%–66%) and hazard ratio of 1.11 (95% CI, 1.04–1.18; P=0.003). These patterns were reproduced in several consistency analyses. Conclusions— In HFpEF, the use of nitrates was not associated with improvements in all-cause mortality or heart failure hospitalization.
Childcare, Social Support and Maternal Depression: A Review and Application of Findings

SUMMARY Research indicates both that working-class mothers—who predominate as social work clients in family and child-care cases—are at high risk for depression and that depres sion in mothers is associated with child-care problems which are often severe and may place the child at risk. Social support has also been found to have widely beneficial effects in relation to mortality, physical health and mental health. This paper reviews evidence on the relationship between maternal depression and social support, examines its implications for practice, and applies findings through the devel opment of an assessment schedule. Findings indicate that although social support has beneficial effects in relation to depression it is a highly differentiated concept whose constituent elements work in different ways. These elements have differing significance according to the social circumstances of the mothers. High risk groups are identified, and linked to related significant areas of social support. The implications of these findings for practice are discussed, and an assessment schedule is developed for practice use. These findings and their application for practice are highly significant for social work in view of the preventive and family support dimensions of the Children Act, 1989. Being a mother presents risks to a woman's affective well being. Studies by Brown and his colleagues (Brown et al., 1975; Brown and Harris, 1978) indicate high levels of affective distress, particularly depression, among mothers with children aged six and under (and with three aged under 14). This is reflected in higher usage of the psychiatric services (Kendall, 1976). Other community surveys indicate also that depression is related to deprivation and social problems amongst young mothers (Moss and Plewis, 1977; Richman, 1976). It also has an impact on
A comparison of two models for the prediction of volitional and goal-directed behaviors : a confirmatory analysis approach

The theory of reasoned action (Ajzen and Fishbein 1980) and two versions of theory of planned behavior (Ajzen 1985) are compared in terms of their ability to predict intentions and behavior. Two behaviors are examined: one involves a high degree of volitional control (voting), and the other is goal-directed; i.e., it involves a low degree of volitional control (weight loss)
Iontophoresis of lysophosphatidic acid into rabbit cornea induces HSV-1 reactivation: evidence that neuronal signaling changes after infection.

PURPOSE Lysophosphatidic acid induces neurite retraction; it is also present in tears and aqueous humor. We determined whether lysophosphatidic acid induces HSV-1 reactivation in latently infected rabbits and whether the nerve growth associated protein GAP-43 undergoes posttranslational modification during the course of HSV-1 infection. METHODS Rabbits were infected with HSV-1 and acute infection was documented by slit lamp examination. Corneas of latently infected rabbits were treated with lysophosphatidic acid or lysophosphatidylserine (structurally similar but lacking biological potency). For application to the cornea, these compounds were impregnated into collagen shields, applied as topical drops, or iontophoresed. In another experiment, corneas of latently infected rabbits were either untreated or treated iontophoretically with lysophosphatidic acid, lysophosphatidylserine, or saline. Ocular swabs detected shedding of infectious virus. Western blot and immunoprecipitation identified GAP-43 in corneal extracts and densitometry of silver-stained isoelectric focusing gels measured changes in GAP-43 isoform abundance. RESULTS Iontophoresis of lysophosphatidic acid induced HSV-1 shedding more frequently than lysophosphatidylserine or saline. Viral shedding induced by collagen shield and topical drop administration was low and not significantly different for lysophosphatidic acid and lysophosphatidylserine. Five discrete GAP-43 isoforms predominated in the IEF gels. Most abundant were the pI 4.7 band in uninfected cornea and the pI 5.05 band in latently-infected cornea. Compared to latently-infected cornea, there was no significant change in isoform abundance 1 h after lysophosphatidic acid iontophoresis, but 24 and 72 h later, the pI 5. 05 band was diminished. CONCLUSIONS Lysophosphatidic acid can induce HSV-1 reactivation and changes in GAP-43 pI suggest that posttranslational modifications, possibly related to phosphorylation and ADP-ribosylation, are occurring during HSV-1 latency and after LPA is iontophoretically applied to the cornea. How lysophosphatidic acid-induced signaling, HSV-1 reactivation, and GAP-43 pI are related remains to be determined.
Learning the theory of harmony by just listening

Major ways of mastering the theory of harmony for Western classical music are only concerned with allocating notes on musical scores or both allocating notes and listening to four parts. There have been few studies based on only listening even though learning by listening is also thought as an important and useful method for learning for non-musicians. Therefore, this study aims to realize a system for self-learning the theory of harmony based on only listening. The possibility of learning the theory based on only listening was investigated. Specifically, an experiment using the 2AFC method was conducted by eight listeners to evaluate whether presented sounds of four parts violated any rules in the theory. Stimuli were synthesized by combining two temperaments, six rules, the timbre, and the pattern of the allocation of notes. The six rules were out of scale, sustained tone, other sustained tone, contrary motion, parallel 5th, and position (open, close, or octave). The results show that (1) there was a significant difference of difficulty in finding rule violations and (2) out of scale rule violations were easy to find whereas position rule violations were hard to find. Therefore, four criteria were used for judging the validity of four parts (i) pitch of a part on a single chord, (ii) progression of a part, (iii) interval between two parts on a single chord, and (iv) progression of two parts on successive chords. Because most of the rules were concerned with these four criteria, the self-learning system is thought to be designed in accordance with those four criteria.
QUALITY BY DESIGN (QBD): A COMPREHENSIVE UNDERSTANDING OF IMPLEMENTATION AND CHALLENGES IN PHARMACEUTICALS DEVELOPMENT

Pharmaceutical industry is constantly looking for ways to ensure and enhance product safety, quality and efficacy. However, drug recalls, manufacturing failure cost, scale up issues and regulatory burden in recent past suggest otherwise. In traditional quality by testing (QbT) approach, the product quality and performance are predominantly ensured by end product testing, with limited understanding of the process and critical process parameters. Regulatory bodies are therefore focusing on implementing quality by design (QbD), a science based approach that improves process understanding by reducing process variation and the enabling process-control strategies. In this regards, pharmaceutical industry is currently undergoing a significant transformation to streamline their R&D process, provide greater manufacturing flexibility and control, and to reduce regulatory burden. However, there is limited understanding and major concerns regarding the implementation of QbD principles in the pharmaceutical arena. The objective of this review article is therefore to provide a comprehensive understanding on various aspects of QbD, along with addressing the concerns related to its implementation.
Possibilistic definitions of security-an assembly kit

We present a framework in which different notions of security can be defined in a uniform and modular way. Each definition of security is formalized as a security predicate by assembling more primitive basic security predicates. A collection of such basic security predicates is defined and we demonstrate how well-known concepts like generalized non-interference or separability can be constructed from them. The framework is open and can be extended with new basic security predicates using a general schema. We investigate the compatibility of the assembled definitions with system properties apart from security and propose a new definition of security which does not restrict non-critical information flow. It turns out that the modularity of our framework simplifies these investigation. Finally, we discuss the stepwise development of secure systems.
Prednisone therapy for children with newly diagnosed idiopathic thrombocytopenic purpura: A randomized clinical trial

The efficacy of corticosteroids in childhood acute idiopathic thrombocytopenic purpura (ITP) is controversial and has infrequently been evaluated in a controlled randomized fashion. We administered prednisone (2 mg/ kg/day for 14 days with subsequent tapering and discontinuation by day 21) or placebo to 27 children, aged 10 years or less, with newly diagnosed ITP. Platelet count, bleeding time (a test of the integrity of the platelet-microvasculature interaction), and clinical bleeding score (based on a 0–4 scale) were determined before (day 0) and six times following initiation of drug therapy (days 1–2, 3–5, 7, 14, 21, and 28). There were no statistically significant (p < 0.05) differences between the two treatment groups in any of the three study parameters except on day 7 of therapy when children receiving prednisone had higher platelet counts and lower bleeding scores and bleeding times than those taking placebo. Bleeding time correlated inversely with the platelet count in both treatment groups. Prednisone did not appear to influence bleeding time independent of its effect on platelet count. This treatment regimen of prednisone did not clearly improve hemostasis in childhood acute ITP except transiently at the end of 1 week of treatment.
Making the Invisible Visible: A Cross‐Sector Analysis of Gender‐Based Leadership Barriers

Despite an abundance of educated, qualified women in the workforce, they continue to be underrepresented at the top of institutional leadership hierarchies. Theories of gendered organizations explain that work processes reproduce gendered structures of society in the workplace. These processes advantage men while forming barriers to women's success. This paper extends critical human resource development (HRD) theory by applying the concept of sexism hidden in the workplace to leadership and by outlining both social and organizational practices that create gender inequities in leadership. Our cross-sector analysis of women leaders in religion and higher education revealed twenty-seven gender-based leadership barriers which operate at the macro, meso, and micro levels of society. We argue that most current efforts to promote women into leadership focus one by one on only a few barriers, primarily those within organizations, while failing to take into account the wide variety of barriers and their prevalence across all societal levels. We offer strategies to address barriers across all three levels to help organizations create gender-equitable leadership environments.
GENERATION IN ITSELF OR FOR ITSELF?

ABSTRACT The concept of welfare generation and the idea of possible conflicts between generations have been discussed frequently in the context of pension systems. In order to form interest groups that could engage in such a conflict, the generations in question would have to form clear collectives with strong agendas. This article shows that the concept of generation is rather vague and that it is not possible to define a generational collective characterised by its experiences with and attitudes towards the welfare state or the pension system. Pensioner cohorts have so far been identified mainly on the basis of financial transactions. If other resources and characteristics are taken into account, the seemingly clear-cut differences between generations get blurred. Apart from these external factors, there is also no evidence to be found for specific generations perceiving themselves as winners or losers, nor do they show an outspoken conflict potential that would mark them as actors in generational disputes.
Stromal Cell-Mediated Stimulation of Osteoclastogenesis

Abstract In the bone marrow microenvironment, stromal cells or their products are known to regulate proliferation and differentiation of hematopoietic stem cells. The purpose of this investigation was to characterize stroma-mediated effects of differentiation-inducing factors on osteoclastogenesis in defined murine cultures. Hematopoietic progenitors (derived from long-term bone marrow cultures, LTBMCs) were cocultured with cloned stromal cell lines to demonstrate the indirect effects of various differentiation-inducing factors. Osteoclastogenesis was compared in three murine marrow systems (whole bone marrow, progenitors cultured alone, and cocultures of progenitors with stromal cell lines) by analysis of multinuclearity and tartrate-resistant acid phosphatase (TRAP) activity. The cultures were treated for two weeks with murine recombinant GM-CSF (5 U/ml), 1,25-dihydroxyvitamin D3 (10-8 M), or parathyroid hormone (PTH, 10-8 M). In whole bone marrow cultures, osteoclast differentiation was stimulated by GM-CSF, PTH and 1,25-dihydroxyvitamin D3. With progenitors alone, only GM-CSF promoted osteoclastogenesis. Each agent stimulated osteoclastogenesis in cocultures of progenitors with a stromal cell line (GBLneor). Thus, the coculture system is a partially defined model for whole bone marrow cultures. In contrast, progenitors that were cocultured with a stromal cell line derived from an osteopetrotic op/op mouse failed to differentiate in the presence of PTH or 1,25-dihydroxyvitamin D3. These results indicate that stimulation of osteoclastogenesis by PTH or 1,25-dihydroxyvitamin D3 is mediated indirectly through factors present in normal marrow stromal cells and that an osteopetrotic stromal cell line failed to support differentiation.
Veterinary drugs residues: a review of the latest analytical research on sample preparation and LC-MS based methods

ABSTRACT The world population is increasing and there is a growing demand for food, leading to intensification of farming methods and a requirement for more coadjuvants. Potential high profits sometimes lead to fraudulent use of drugs and pesticides. Veterinary drugs in particular can pose a real risk to human health if their residues are allowed to enter the food chain. Parent drugs and their metabolites can occur in foodstuffs individually or as multicomponent mixtures with enhanced adverse effects. In order to protect consumer safety, the European Union has established lists of forbidden substances, maximum residue limits for authorised drugs and precise criteria for confirmation analyses and interpretation of the results. Due to their nature and potential danger, the ‘best available technique’ should always be applied. Following this principle, this review examines the procedures and techniques applied to monitoring pharmaceutical products of major concern (e.g. anthelmintics, NSAIDs, corticosteroids, coccidiostats) in foods of animal origin, discussing advances over the past five years and future trends in the field of food safety. Our goal was both to focus attention on this important topic and to provide a selection of the most relevant recent papers on drug residues in foodstuffs. Graphical Abstract
Serum levels of the soluble haemoglobin scavenger receptor CD163 in MPO-ANCA-associated renal vasculitis

Objectives: The contribution of infections to the mortality of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is important, and early and careful infection control is necessary. We investigated the usefulness of the serum-soluble haemoglobin scavenger receptor CD163 for detecting the presence of infectious complications regardless of disease activity. Method: Soluble CD163 in serum obtained from 45 Japanese patients with myeloperoxidase (MPO)-AAV was measured by an enzyme-linked immunosorbent assay (ELISA). We evaluated 36 samples from active-vasculitis patients, 36 samples from inactive-vasculitis patients without infection, and 19 samples from inactive-vasculitis patients with infectious complications. Serum-soluble CD163 was also measured in 15 infectious patients without vasculitis and in 30 normal controls. Results: The mean serum-soluble CD163 level was higher in the patients with infectious complications than in the active-vasculitis patients, inactive-vasculitis patients, and normal controls. There were significant positive correlations between serum-soluble CD163 levels and white blood cell (WBC) count, serum C-reactive protein (CRP) levels, and serum albumin levels, but only serum CRP levels were correlated with serum-soluble CD163 levels in a multiple regression analysis. On the receiver-operating characteristic (ROC) curve, serum-soluble CD163 levels had 80.6% sensitivity and 86.7% specificity for differentiating patients with infection from those without infection. Among the active-vasculitis patients, the mean serum-soluble CD163 level of the patients with alveolar haemorrhage was significantly lower than that of the patients with interstitial lung diseases and that of the patients without pulmonary lesions. Conclusions: The serum-soluble CD163 level may be a useful marker for the detection of infectious complications in MPO-AAV patients.
The future of online social interactions: what to expect in 2020

Blogs, wikis, tagging, podcasts, and social networking websites such as MySpace, Facebook, Flickr and YouTube have radically changed user interactions on the World Wide Web from a static, one-way, consumption model to a dynamic, multi-way, participation model. Broad user power and flexibility have changed how people engage in and experience their interconnections, interests, and collaborations. Online social interactions will evolve in the next decade to address the growing needs of its user community and make entries into many aspects of our lives. This evolution may very well be among the most exciting ones of our times where the individual and collective power of people to contribute and share content, experiences, ideas, expertise etc. may be even more enhanced than it is today. The enhancement may be shaped through a better understanding of user needs and behavior and it may be enabled through the seamless convergence of multi-modal technologies, new applications, new domains, data mining and better navigational and search capabilities. Some of these changes will also permeate into the workplace and change the way we work. This panel will discuss how online social interactions may evolve in the next decade and what impact it may have on diverse dimensions in our world.
Computer Use, Sleep Difficulties, and Psychological Symptoms Among School-Aged Children: The Mediating Role of Sleep Difficulties

Background: Previous studies have indicated that electronic media use may affect the health of school-aged children. Objectives: This study aimed to examine the association between computer use and psychological symptoms among Italian adolescents, taking into account the mediating role of difficulty in getting to sleep. Patients and Methods: This study used data from 23,941 15-year-old students participating in the health behavior in school-aged children survey (mean age, 15.7 years; 50.1% girls). Self-completed questionnaires were administered in classrooms. Measures included computer use, psychological symptoms, and difficulty in getting to sleep. Structural equation modeling was used to investigate the associations among variables. Results: On average, students spent approximately 2 hours per day using computers and about one-third of the sample reported weekly psychological symptoms (feeling low, irritable, and nervous). Further, 15.8% of Italian adolescents reported experiencing difficulties in getting to sleep more often than once a week or almost daily over the last six months. The structural equation model showed that more frequent computer use was associated with a higher frequency of psychological symptoms in adolescents, and the difficulty in getting to sleep partly mediated this association. Conclusions: Overall, these results indicate the role of computer use in influencing the sleep quality and health of adolescents. Educational programs are recommended to increase awareness among families and students of the effects of computer use and sleep habits on health.
Developmental Potential of Bovine Androgenetic and Parthenogenetic Embryos: A Comparative Study1

Abstract In this study, we compared the developmental capacity of bovine haploid and diploid androgenetic and parthenogenetic embryos obtained by different methods. Androgenetic embryos were produced by piezo-intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF) of enucleated oocytes with or without subsequent pronuclear transfer from one haploid zygote to another. Parthenogenetic embryos were obtained by activation of matured oocytes by ionomycin combined with cycloheximide or 6-dimethylaminopurine (DMAP) treatment. Only few cleaved androgenetic haploid embryos were able to compact (2.7%) and to form blastocysts (1.8%), while significantly more haploid parthenogenotes underwent compaction (24–37%) and a minority developed to blastocysts at different rates, depending on the activation procedure (cycloheximide 3%, 6-DMAP 14.5%). By contrast, development to blastocyst of diploid androgenotes, cloned androgenetic embryos, and parthenogenotes (31%, 39%, and 43%, respectively) was similar to IVF control embryos (35%). Cell number on Day 7 was higher for IVF blastocysts and decreased in consecutive order in diploid androgenotes, diploid parthenogenotes, and haploid uniparental embryos. Following transfer of diploid androgenetic embryos, a pregnancy was established and maintained up to Day 28.