Miracle-dz/UniFAR-FTUs huggingface dataset:
Vaccination of mice against experimental Neospora caninum infection using NcSAG1- and NcSRS2-based recombinant antigens and DNA vaccines

NcSAG1 and NcSRS2, the two major immunodominant tachyzoite surface antigens of the apicomplexan parasite Neospora caninum, were investigated for their potential as vaccine candidates in mice. Recombinant recNcSRS2 and recNcSAG1 were expressed in Escherichia coli as poly-histidine-tagged fusion proteins. Separate groups of mice were immunized with purified recNcSAG1, recNcSRS2, or a combination of both, and were then challenged with N. caninum tachyzoites. Subsequent experiments included intramuscular vaccination of mice with the eukaryotic expression plasmid pcDNA3 containing either NcSRS2 or NcSAG1 cDNA inserts, followed by a single booster with the corresponding recombinant antigens. Immunization with a crude somatic antigen (NC1-extract) was included in the experiments. Following challenge, the presence of the parasite in the different organs was assessed by a N. caninum-specific PCR, while the parasite burden in infected brain tissue was assessed by quantitative real-time PCR. Immunization of mice employing individual recombinant antigens, or combined recNcSAG1/recNcSRS2, resulted in a lower degree of protection against cerebral infection, when compared to combined DNA/recombinant antigen vaccination. Serological analysis showed that this protective effect was associated with the occurrence of antibodies directed against native parasite antigens in those animals receiving combined DNA/recombinant antigen vaccination. Conversely, mice immunized with recombinant antigens alone generated antibodies recognizing only the recombinant antigens. Mice experiencing clinical signs such as walking disorders, rounded back, apathy and paralysis were observed only in the untreated positive control groups, but never in the vaccinated groups. Our results suggest that a combined DNA/recombinant antigen-vaccine, based on NcSAG1 and NcSRS2, respectively, exhibited a highly significant protective effect against experimentally induced cerebral neosporosis in mice.
Acute exudative paraneoplastic polymorphous vitelliform maculopathy in five cases.

BACKGROUND AND OBJECTIVE To evaluate clinical features, course, and outcome of patients with acute exudative paraneoplastic polymorphous vitelliform maculopathy (AEPPVM). PATIENTS AND METHODS Retrospective case series of 5 patients. RESULTS There were 3 males and 2 females, with a median age of 74 years. The primary neoplasms were cutaneous melanoma (n = 2), choroidal melanoma (n = 1), lung adenocarcinoma (n = 1), and lung plus breast adenocarcinoma (n = 1). The mean interval between the diagnosis of the primary neoplasm and the diagnosis of AEPPVM was 42 months. The presenting symptom was blurred vision in all cases. Ophthalmoscopy disclosed multifocal localized shallow serous detachments of the post-equatorial neurosensory retina with yellow-white subretinal debris confirmed by optical coherence tomography (OCT). There was a mean of 21 individual sites of detachment per eye, each measuring a mean of approximately 0.8 millimeter in diameter. Fundus autofluorescence depicted hyperautofluorescence corresponding to the detachments. After mean follow-up of 5 months, three patients had died of metastases. Of the two survivors, one showed resolution of lesions and the other was unchanged. CONCLUSION AEPPVM is a paraneoplastic retinopathy found in patients with metastatic melanoma or carcinoma. The most salient feature is reduced visual acuity from multifocal shallow retinal detachments less than 1-mm diameter, best depicted on OCT.
Electroconvulsive Therapy in the Republic of Ireland 1982: A Summary of Findings

In 1981, Pippard & Ellam published the findings of their survey of electroconvulsive treatment (ECT) in Great Britain. This was the first such survey to use a ‘medical audit’ approach, and included field visits to ECT clinics and a three-month uncontrolled outcome study of patients. They reported that ECT was used selectively, but that equipment, administration of the treatment, and clinic premises left much to be desired.
Constitutive IFN-alpha/beta signal for efficient IFN-alpha/beta gene induction by virus.

Efficient IFN-alpha/beta gene induction in virus-infected cells is an event central to innate immunity, in which the transcription factor IRF-7 plays a critical role together with IRF-3. Unlike IRF-3, IRF-7 is short-lived and its gene expression is dependent on IFN-alpha/beta signalling; hence, the signal-dependent enhancement of IRF-7 gene induction during viral infection is essential for positive-feedback regulation of IFN-alpha/beta gene induction. Here, we provide evidence that constitutive, IRF-3/IRF-7-independent production of IFN-alpha/beta in uninfected cells is critical for setting the IRF-7 expression levels, determining whether or not the positive-feedback mechanism will operate effectively upon viral infection. In fact, spleen cells are more dependent than fibroblasts on this mechanism; the IFN-alpha/beta gene induction is impaired more severely by blocking the IRF-7 induction pathway than by introducing an IRF-3 null mutation. Thus, the constitutive IFN-alpha/beta signal provides a foundation for the IRF-7-mediated enhancement of its own production in response to virus infection.
Participation Experiences and Civic Concepts, Attitudes and Engagement: Implications for Citizenship Education Projects

This article considers participation experiences of 14 year-old and upper secondary students in six European countries that were involved in the International Association for the Evaluation of Educational Achievement (IEA) Civic Education Study: the Czech Republic, Norway, Portugal, Slovenia, Sweden and Switzerland, countries that vary in their history of institution of democratic regimes. Participation has been considered as a crucial dimension of citizenship, and experiences within civil society are viewed as a relevant opportunity for developing personal and social resources essential for the survival and expansion of democracy. Additionally, participation experiences in adolescence seem to be a good predictor of political engagement during adult life. Results show that participation is most evident in organisations that provide enrichment activities (sports, music, computers), but both 14 year-old and upper secondary students are involved in voluntary activities, in some civic-related organisations (mainly Scouts, religious affiliated and environmental), and in experiences within the school (with student councils and school newspapers at the top). However, cross-national and cross-age variations are significant. Overall, there seems to be a positive impact of the frequency of students' involvement on civic concepts, attitudes and engagement, but results also reveal that more is not necessarily better. The most relevant implication for the development of citizenship education projects is that ‘action’ can be a powerful learning tool but only if it is intentionally designed and systematically supported: the quality of participation experiences, both in terms of meaningful involvement, of interaction with (different) others, and opportunities for personal integration, is therefore crucial if the goal is to promote the personal empowerment and social pluralism on which the essence of democracy relies.
Indoleamine 2,3-dioxygenase in cancer: targeting pathological immune tolerance with small-molecule inhibitors

Indoleamine 2,3-dioxygenase (IDO) is an interferon (IFN)-γ-inducible, extrahepatic enzyme that catalyses the initial and rate-limiting step in the degradation of the essential amino acid tryptophan. Elevated tryptophan catabolism mediated by IDO is associated with a wide variety of human cancers and has historically been thought to be a tumoricidal consequence of IFN-γ exposure. Evidence of a physiological requirement for IDO activity in protecting the allogeneic fetus from rejection by the maternal immune system has stimulated a radical shift in thinking about the role of IDO in cancer. Evidence now suggests that tumours can exploit IDO-mediated peripheral tolerance to promote immune escape. This review summarises key studies that implicate IDO as an important mediator of peripheral immune tolerance as well as the development of a promising new anticancer modality that incorporates the use of IDO inhibitors. The second part focuses on the current state of development of IDO inhibitory compounds as potential pharmaceutical agents.
Multiple myeloma and family history of lymphohaematopoietic cancers: Results from the International Multiple Myeloma Consortium

Family clusters of multiple myeloma (MM) suggest disease heritability. Nevertheless, patterns of inheritance and the importance of genetic versus environmental risk factors in MM aetiology remain unclear. We pooled data from eleven case‐control studies from the International Multiple Myeloma Consortium to characterize the association of MM risk with having a first‐degree relative with a history of a lympho‐haematapoietic cancer. Unconditional logistic regression models, adjusted for study, sex, age and education level, were used to estimate associations between MM risk and having a first‐degree relative with a history of non‐Hodgkin lymphoma, Hodgkin lymphoma, leukaemia or MM. Sex, African American race/ethnicity and age were explored as effect modifiers. A total of 2843 cases and 11 470 controls were included. MM risk was elevated in association with having a first‐degree relative with any lympho‐haematapoietic cancer (Odds Ratio (OR) = 1·29, 95% Confidence Interval (CI): 1·08–1·55). The association was particularly strong for having a first‐degree relative with MM (OR = 1·90, 95% CI: 1·26–2·87), especially among men (OR = 4·13, 95% CI: 2·17–7·85) and African Americans (OR = 5·52, 95% CI: 1·87–16·27). These results support the hypothesis that genetic inheritance plays a role in MM aetiology. Future studies are warranted to characterize interactions of genetic markers with environmental exposures.
Studies on alcohol diuresis. I. The effect of ethyl alcohol ingestion on water, electrolyte and acid-base metabolism.

The diuresis following the ingestion of alcohol has been compared with the increased urine flow secondary to water ingestion (1). Van Dyke and Ames (2) demonstrated that the injection of small amounts of alcohol (12 to 50 mg. per Kg.) into the carotid artery of normal unanesthetized dogs evoked a prompt diuresis without any detectable alcohol in the systemic venous blood. No increased diuresis occurred in dogs with diabetes insipidus following intracarotid injection. As alcohol has no direct effect on exogenous antidiuretic hormone (ADH), or on the responsiveness of the renal tubules to this hormone (3), most investigators agree that "alcohol diuresis" is probably due to suppression of the release of ADH. Little attempt has been made, however, to correlate simultaneously its effect on water excretion with electrolyte excretion, acid-base changes, and al-terations in blood volume. The study was divided into three parts: Part I. Effect of alcohol ingestion on water, electrolyte, and acid-base metabolism in semi-recumbent hydrated normal subjects; Part II. Evaluation of the inhibition of ADH secretion by alcohol, in normal subjects in whom acute changes of extracellular fluid tonicity and "effective circulating blood volume" were induced; Part III. Evaluation in pathologic states in which abnormal function of the neurohypophyseal system had been demonstrated or postulated.
Clinical features and risk factors for mortality in Aeromonas bacteremic adults with hematologic malignancies.

BACKGROUND AND PURPOSE Aeromonas spp. often cause infections in immunocompromised patients. To specifically understand the clinical features of Aeromonas bacteremic adults with hematologic malignancies, we investigated the demographic, clinical and microbiologic characteristics of Aeromonas bacteremia in this patient population. METHODS Retrospective study performed in a tertiary medical center in southern Taiwan, in which adults with hematologic malignancies suffered from Aeromonas bacteremia admitted between 1995 and 2003 were included for study. RESULTS There were 45 episodes of Aeromonas bacteremia in 41 adults with hematologic malignancies. Episodes of Aeromonas bacteremia which occurred at least 2 months apart were counted as separate cases in the analysis. A total of 30 men and 15 women (mean age: 53.2 years), with 4 patients experiencing 2 episodes, was included. The 3 leading underlying hematologic malignancies were acute myelogenous leukemia (37.8%), myelodysplastic syndrome (26.7%) and non-Hodgkin's lymphoma (17.8%). No cluster of Aeromonas bacteremia was found during the study period. Twenty nine (64.4%) of the 31 patients with nosocomial Aeromonas bacteremia had received recent antineoplastic chemotherapy. The 3 leading clinical manifestations were fever (88.9%), septic shock (40%), and altered consciousness (26.7%). Eleven (24.4%) episodes of bacteremia were polymicrobial. Sixteen (35.6%) patients died within 14 days of onset of bacteremia. The mean duration from sampling blood for culture to death was 3.81 days. Altered consciousness (odds ratio, 8.999; 95% confidence interval, 1.787-45.33; p=0.008) was the only independent prognostic factor for mortality. High resistance rates (11.1% to piperacillin and 35.6% to imipenem) among Aeromonas isolates were also noted. CONCLUSION In febrile patients with hematologic malignancies and suspected Aeromonas infections, particular attention to the development of alteration of consciousness is needed as it is an independent risk factor for mortality.
Eotaxin (CCL11) and Eotaxin-2 (CCL24) Induce Recruitment of Eosinophils, Basophils, Neutrophils, and Macrophages As Well As Features of Early- and Late-Phase Allergic Reactions Following Cutaneous Injection in Human Atopic and Nonatopic Volunteers1

Eotaxin and eotaxin-2, acting through CCR3, are potent eosinophil chemoattractants both in vitro and in animal models. In this study we examined the capacity of eotaxin and eotaxin-2 to recruit eosinophils and other inflammatory cells in vivo in human atopic and nonatopic skin. Skin biopsies taken after intradermal injection of eotaxin and eotaxin-2 were examined by immunohistochemistry. Allergen- and diluent-challenged sites were used as positive and negative controls. Eotaxin and eotaxin-2 produced a dose- and time-dependent local eosinophilia of comparable intensity in both atopic and nonatopic individuals. This was associated with an acute wheal and flare response at the site of injection and development of a cutaneous late phase reaction in a proportion of subjects. There was an accompanying decrease in mast cell numbers. Both chemokines also induced the accumulation of basophils and an unexpected early infiltration of neutrophils. Macrophages were prominent at the 24-h point. Although there was surface CCR3 expression on neutrophils in whole blood, we were unable to demonstrate any functional neutrophil responses to eotaxin in vitro. Thus, intradermal injection of eotaxin and eotaxin-2 in humans induced infiltration of eosinophils and other inflammatory cells as well as changes consistent with CC chemokine-induced mast cell degranulation.
FOLLOW UP STUDY OF RADIOCESIUM CONTAMINATION IN A GREEK FOREST ECOSYSTEM

Radiocesiun distribution in the different parts of a Quercus conferta Kit ecosystem in Northern Greece was measured in 2005–2006, twenty years after the Chernobyl accident. The comparison between the results of this study and those previously measured (1993–1995) in the same ecosystem gives information about the long-term behavior of 137Cs in forest ecosystems. The major part of the 137Cs inventory is still in the upper layers of the soil. The radiocesium distribution in soil is fixed and has been in equilibrium at least since 1993, when the first measurements were performed. The major contamination mechanism of leaves and wood is root uptake.
Long-term survival in idiopathic membranous glomerulonephritis: can the course be clinically predicted?

72 adult patients with idiopathic membranous glomerulonephritis (iMGN), 92% having proteinuria 3 g/24 h or more, were studied for the clinical evolution of the disease and factors which might be involved in the development of chronic renal insufficiency (CRI). At 10 years, 46% were in complete or partial remission, 4% had the nephrotic syndrome (NS), 26% had some degree of CRI, and 24% were dead or started on dialysis. The actuarial patient and kidney survival rates were 80% and 64%, respectively at 10 years. Patient survival rate was not affected by gender, age (after adjustment for age- and sex-matched population) or the severity of NS at diagnosis. 20 patients showed CRI and apart from the more frequent (p < 0.05) presence of CRI at diagnosis, no clinical features discriminated them from those having intact renal function. Furthermore, no clinical factors at diagnosis predicted the final renal function among the 72 patients. However, it appeared that the evolution of clinical status of iMGN was rapid CRI appearing 1.4 (median, range from 0 to 15.1) years after the diagnosis. At one and two years, renal function correlated significantly (r = 0.54, p < 0.0001 at two years) with the final renal function. What is more, the type of the evolution of proteinuria over the first two years gave valuable information on the eventual deterioration of renal function. Patients having stable non-nephrotic grade proteinuria and those in whom NS disappeared, had excellent renal outcome while those in particular showing an increased severity of NS had poor prognosis in terms of renal survival. (ABSTRACT TRUNCATED AT 250 WORDS)
Spx (YjbD), a negative effector of competence in Bacillus subtilis, enhances ClpC–MecA–ComK interaction

ComK, a key transcriptional regulator in the development of competence in Bacillus subtilis, is required for its own transcription as well as that of the late competence genes encoding proteins involved in DNA uptake. ComK is sequestered in a complex with ClpC and MecA until a peptide, ComS, accumulates in cells. ComS releases ComK from the inhibitory complex, thus allowing ComK to carry out its function as a transcriptional activator. Spx (formerly YjbD), a negative effector of competence, accumulates in clpP mutants. High concentrations of Spx may be responsible for the inability of clpP mutants to become competent because spx mutations are able to restore competence in the clpP mutant. In this paper, we showed, based on in vitro experiments, that Spx forms a quaternary complex with ClpC, MecA and ComK and enhances ComK binding to ClpC–MecA. Two ComS alanine substitution mutants (I13A and W43A), previously shown to be defective in vivo, were less efficient in releasing ComK from ClpC–MecA. The I13A mutant with a weaker binding affinity to MecA was inefficient in releasing ComK regardless of whether Spx was present. In contrast, the defect of the W43A mutant in dissociating ComK was more readily observed in the presence of Spx. Spx is a highly conserved protein among Gram‐positive bacteria, in which it may function closely with the protease adaptor protein, MecA.
Metabolic improvements in obese type 2 diabetes subjects implanted for 1 year with an endoscopically deployed duodenal-jejunal bypass liner.

BACKGROUND The purpose of this study was to evaluate the effect of the duodenal-jejunal bypass liner (DJBL), a 60-cm, impermeable fluoropolymer liner anchored in the duodenum to create a duodenal-jejunal bypass, on metabolic parameters in obese subjects with type 2 diabetes. METHODS Twenty-two subjects (mean age, 46.2±10.5 years) with type 2 diabetes and a body mass index between 40 and 60 kg/m(2) (mean body mass index, 44.8±7.4 kg/m(2)) were enrolled in this 52-week, prospective, open-label clinical trial. Endoscopic device implantation was performed with the patient under general anesthesia, and the subjects were examined periodically during the next 52 weeks. Primary end points included changes in fasting blood glucose and insulin levels and changes in hemoglobin A1c (HbA1c). The DJBL was removed endoscopically at the end of the study. RESULTS Thirteen subjects completed the 52-week study, and the mean duration of the implant period for all subjects was 41.9±3.2 weeks. Reasons for early removal of the device included device migration (n=3), gastrointestinal bleeding (n=1), abdominal pain (n=2), principal investigator request (n=2), and discovery of an unrelated malignancy (n=1). Using last observation carried forward, statistically significant reductions in fasting blood glucose (-30.3±10.2 mg/dL), fasting insulin (-7.3±2.6 μU/mL), and HbA1c (-2.1±0.3%) were observed. At the end of the study, 16 of the 22 subjects had an HbA1c<7% compared with only one of 22 at baseline. Upper abdominal pain (n=11), back pain (n=5), nausea (n=7), and vomiting (n=7) were the most common device-related adverse events. CONCLUSIONS The DJBL improves glycemic status in obese subjects with diabetes and therefore represents a nonsurgical, reversible alternative to bariatric surgery.
Statistical Significance of the Netflix Challenge

Inspired by the legacy of the Netflix contest, we provide an overview of what has been learned---from our own efforts, and those of others---concerning the problems of collaborative filtering and recommender systems. The data set consists of about 100 million movie ratings (from 1 to 5 stars) involving some 480 thousand users and some 18 thousand movies; the associated ratings matrix is about 99% sparse. The goal is to predict ratings that users will give to movies; systems which can do this accurately have significant commercial applications, particularly on the world wide web. We discuss, in some detail, approaches to "baseline" modeling, singular value decomposition (SVD), as well as kNN (nearest neighbor) and neural network models; temporal effects, cross-validation issues, ensemble methods and other considerations are discussed as well. We compare existing models in a search for new models, and also discuss the mission-critical issues of penalization and parameter shrinkage which arise when the dimensions of a parameter space reaches into the millions. Although much work on such problems has been carried out by the computer science and machine learning communities, our goal here is to address a statistical audience, and to provide a primarily statistical treatment of the lessons that have been learned from this remarkable set of data.
Sleep-disordered breathing, type 2 diabetes and the metabolic syndrome

Sleep-disordered breathing (SDB) encompasses a spectrum of conditions that can lead to altered sleep homeostasis. In particular, obstructive sleep apnoea (OSA) is the most common form of SDB and is associated with adverse cardiometabolic manifestations including hypertension, metabolic syndrome and type 2 diabetes, ultimately increasing the risk of cardiovascular disease. The pathophysiological basis of these associations may relate to repeated intermittent hypoxia and fragmented sleep episodes that characterize OSA which drive further mechanisms with adverse metabolic and cardiovascular consequences. The associations of OSA with type 2 diabetes and the metabolic syndrome have been described in studies ranging from epidemiological and observational studies to controlled trials investigating the effects of OSA therapy with continuous positive airway pressure (CPAP). In recent years, there have been rising prevalence rates of diabetes and obesity worldwide. Given the established links between SDB (in particular OSA) with both conditions, understanding the potential influence of OSA on the components of the metabolic syndrome and diabetes and the underlying mechanisms by which such interactions may contribute to metabolic dysregulation are important in order to effectively and holistically manage patients with SDB, type 2 diabetes or the metabolic syndrome. In this article, we review the literature describing the associations, the possible underlying pathophysiological mechanisms linking these conditions and the effects of interventions including CPAP treatment and weight loss.