Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypoxia Preconditioning in the Brain

Exposure to moderate hypoxia alone does not cause neuronal death as long as blood pressure and cerebral blood flow are maintained in mammals. In neonatal and adult mammals including rats and mice, carotid occlusion in combination with hypoxia produces neuronal death and brain infarction. However, preexposure to 8% oxygen for 3 h protects the brain and likely other organs of neonatal and adult rats against combined hypoxia-ischemia 24 h later. In this paper, the possible mechanisms of this so-called hypoxia-induced tolerance to ischemia is discussed. One mechanism likely involves hypoxia-inducible factor-1α (HIF-1α). HIF-1α is a transcription factor that – during hypoxia – binds with a second protein (HIF-1β) in the nucleus to promoter elements in hypoxia-responsive target genes. This causes upregulation of HIF target genes including VEGF, erythropoietin, iNOS, glucose transporter-1, glycolytic enzymes, and many other genes to protect the brain against ischemia 24 h later. In addition, non-HIF pathways including MTF-1, Egr-1 and others act directly or indirectly on other target genes to also promote hypoxia-induced preconditioning. Hypoxia preconditioning can be mimicked by iron chelators like desferrioxamine and transition metals like cobalt chloride that inhibit prolyl hydroxylases, increase HIF-1α levels in the brain, and produce protection of the brain against combined hypoxia-ischemia 24 h later. This hypoxia preconditioning has potential clinical usefulness in protecting high-risk newborns or to provide protection prior to surgery.
Dynamical conifold transitions and moduli trapping in M-theory cosmology

We study five-dimensional Kasner cosmologies in the vicinity of a conifold locus occurring in a time-dependent Calabi–Yau compactification of M-theory. The dynamics of M2-brane winding modes, which become light in this region, is taken into account using a suitable gauged supergravity action. We find cosmological solutions which interpolate between the two branches of the transition, establishing that conifold transitions can be realized dynamically. However, generic solutions do not correspond to transitions, but to the moduli being trapped close to the conifold locus. This effect results from an interplay between the scalar potential and Hubble friction. We show that the dynamics does not depend on the details of the potential, but only on its overall shape.
Bayesian varying-coefficient models using adaptive regression splines

Varying-coefficient models provide a flexible framework for semi- and nonparametric generalized regression analysis. We present a fully Bayesian B-spline basis function approach with adaptive knot selection. For each of the unknown regression functions or varying coefficients, the number and location of knots and the B-spline coefficients are estimated simultaneously using reversible jump Markov chain Monte Carlo sampling. The overall procedure can therefore be viewed as a kind of Bayesian model averaging. Although Gaussian responses are covered by the general framework, the method is particularly useful for fundamentally non-Gaussian responses, where less alternatives are available. We illustrate the approach with a thorough application to two data sets analysed previously in the literature: the kyphosis data set with a binary response and survival data from the Veteran’s Administration lung cancer trial.
PROTECTIVE EFFECT OF MORINGA PEREGRINA LEAVES EXTRACT ON ACETAMINOPHEN -INDUCED LIVER TOXICITY IN ALBINO RATS

Background: Acetaminophen is a common antipyretic drug but at overdose can cause severe hepatotoxicity that may further develop into liver failure and hepatic centrilobular necrosis in experimental animals and humans. This study was undertaken to assess the ameliorative role of Moringa peregrina leaves extract against acetaminophen toxicity in rats. Materials and methods: Induction of hepatotoxicity was done by chronic oral administration of acetaminophen (750 mg/kg bwt) for 4 weeks. To study the possible hepatoprotective effect, Moringa peregrina leaves extract (200 mg/kg bwt) or Silymarin (50 mg/kg bwt) was administered orally, for 4 weeks, along with acetaminophen. Results: acetaminophen significantly increased serum liver enzymes and caused oxidative stress, evidenced by significantly increased tissue malondialdehyde, glutathione peroxidase, hepatic DNA fragmentation, and significant decrease of glutathione and antioxidant enzymes in liver, blood and brain. On the other hand, administration of Moringa peregrina leaves extract reversed acetaminophen-related toxic effects through: powerful malondialdehyde suppression, glutathione peroxidase normalization and stimulation of the cellular antioxidants synthesis represented by significant increase of glutathione, catalase and superoxide dismutase in liver, blood and brain, besides, DNA fragmentation was significantly decreased in the liver tissue. Conclusion: acetaminophen induced oxidative damage can be improved by Moringa peregrina leaves extract-treatment, due to its antioxidant potential.
Treatment patterns in inpatients with bipolar disorder at a psychiatric university hospital over a 9-year period: focus on mood stabilizers

The increasing number of pharmacological treatment options for bipolar disorder seems to be paralleled by the number of evidence-based guidelines published previously. The aim of this study was to systematically examine the adherence to published guidelines and any change in prescription habits over time in a psychiatric hospital setting. This is a retrospective study of 531 bipolar in patients who were consecutively admitted to the Department for Psychiatry and Psychotherapy in Innsbruck. Their complete medical histories were evaluated for psychotropic medications, with a special focus on mood stabilizers (MSs). To compare the use of individual MSs or combinations with other psychotropic medications in two preselected observation periods (1999–2003 and 2004–2007), we used Fisher’s exact test. Overall, the proportion of patients receiving at least one MS increased significantly from 1999–2003 to 2004–2007 (74.1 vs. 83.1%, P=0.011). Among the individual MSs, valproate was used most frequently in both time periods, showing a significant increase (P<0.001). Prescriptions of quetiapine (P<0.001) and lamotrigine (P=0.033) increased significantly, carbamazepine showed a significant decrease (P<0.001). Prescriptions of lithium and olanzapine decreased without reaching significance. The significant increase in the prescription of MS reflects the increasing awareness and implementation of recent evidence-based medicine guidelines into clinical practice. Clinical decision making, usually made on the basis of individual clinical experience, should always be reevaluated using periodically updated evidence-based medicine guidelines.
A cross-sectional investigation of public attitudes toward dementia in Bristol and South Gloucestershire using the approaches to dementia questionnaire

ABSTRACT Background: To date, surveys of attitudes toward dementia have largely been conducted using unvalidated materials or have focused on healthcare professionals supporting people affected by dementia. The aim of this study was to carry out a survey of public attitudes toward people affected by dementia in Bristol and South Gloucestershire. Methods: A survey was carried out using a modified version of the Approaches to Dementia Questionnaire (ADQ). Data from people living outside the area, and people who were working with people affected by dementia were omitted from the analysis. Responses from the remaining 794 ADQ questionnaires were weighted to correct for under-represented age, gender, and ethnic groups. Results: Younger people held more positive attitudes toward dementia than older people. Individuals who identified themselves as White held more positive attitudes than non-White individuals. Individuals with personal experience of dementia held more positive attitudes than those with no experience of dementia. When considering age differences, gender played a role, with younger men having more positive scores than other groups. Conclusions: This is one of the first surveys of public attitudes to dementia to use a validated questionnaire such as the ADQ. The study provides a baseline of attitudes toward dementia for the Bristol and South Gloucestershire areas, against which we will be able to compare changes over time. This is important due to the emphasis in public health campaigns on improving attitudes toward dementia.
Ambiguus motoneurons innervating laryngeal and esophageal muscles are malpositioned in the Reelin-deficient mutant rat, Shaking Rat Kawasaki

Conclusions. The present study confirmed that ambiguus motoneurons innervating intrinsic laryngeal and esophageal muscles are radially malpositioned in the brainstem of the Shaking Rat Kawasaki (SRK), a reelin-deficient mutant rat. Objectives. Ambiguus motoneurons innervating the striated muscles of the larynx and esophagus take a long migration from their original birth plate in the floor of the fourth ventricle to their final settlement in the ventral margin of the medulla oblongata. To examine whether the migration of ambiguus nucleus neurons is affected in SRK, we studied localization of ambiguus motoneurons of postnatal day 21 (P21) normal and SRK rats. Materials and methods. To label ambiguus motoneurons retrogradely, horseradish peroxidase (HRP) was injected into some laryngeal muscles including cricothyroid, thyroarytenoid and posterior cricoarytenoid muscles, and the cervical and abdominal esophageal muscles of the SRK and normal controls 2 days before sacrifice. Results. In the P21 normal rat, HRP-positive laryngeal and esophageal motoneurons were found in the nucleus ambiguus, whereas in the P21 SRK, they were scattered from the base of the fourth ventricle to the ventro-lateral margin of the medulla, suggesting that radial migration of ambiguus motoneurons from their birthplace to their final settlement is guided by Reelin protein.
Patterns of metabolic progression to type 1 diabetes in the Diabetes Prevention Trial-Type 1.

OBJECTIVE There is little information regarding the pattern of metabolic deterioration before the onset of type 1 diabetes. The goal of this study was to utilize data from the Diabetes Prevention Trial-Type 1 (DPT-1) to obtain a picture of the metabolic progression to type 1 diabetes over a period of approximately 2.5 years before its diagnosis. RESEARCH DESIGN AND METHODS Fifty-four DPT-1 participants (22 in the parenteral trial and 32 in the oral trial) were studied. All had oral glucose tolerance tests (OGTTs) at 6-month intervals from approximately 30 to 6 months before diagnosis. The vast majority also had OGTTs at diagnosis. Changes in OGTT glucose and C-peptide indexes from 30 to 6 months before diagnosis were examined by calculating slopes of the indexes for each individual over that time period. Changes from 6 months before diagnosis to diagnosis were examined by paired comparisons of the OGTT metabolic indexes between the time points. RESULTS Glucose levels increased gradually from 30 to 6 months before diagnosis in both the parenteral and oral groups (P < 0.001 for all indexes). Area under the curve (AUC) C-peptide (P < 0.05) and AUC C-peptide-to-AUC glucose ratio (P < 0.001) values decreased in the oral group; peak C-peptide-to-2-h glucose ratio values decreased in both groups (P < 0.001). In participants who also had OGTTs at diagnosis, AUC C-peptide (parenteral group, P < 0.05) and peak C-peptide (oral group, P < 0.05) values decreased from the last 6 months before diagnosis; stimulated C-peptide-to-glucose ratio values decreased in both groups (P < 0.001). Conversely, fasting C-peptide levels increased in both groups (oral group, P < 0.01). Fasting C-peptide-to-fasting glucose ratio values remained constant throughout the 30-month follow-up. CONCLUSIONS These data indicate that over a period of at least 2 years, glucose tolerance gradually deteriorates as stimulated C-peptide levels slowly decline in a substantial number of individuals who develop type 1 diabetes. However, fasting C-peptide levels are maintained, even at diagnosis.
Female Sex and IL28B, a Synergism for Spontaneous Viral Clearance in Hepatitis C Virus (HCV) Seroconverters from a Community-Based Cohort

Background & Aims Since acute hepatitis C virus (HCV) infection is often asymptomatic, it is difficult to examine the rate and determinants of spontaneous clearance. Consequently, these studies are subject to bias, which can potentially lead to biased rates of viral clearance and risk estimates. We evaluated determinants of spontaneous HCV clearance among HCV seroconverters identified in a unique community-based cohort. Methods Subjects were 106 drug users with documented dates of HCV seroconversion from the Amsterdam Cohort Study. Logistic regression was used to examine sociodemographic, behavioral, clinical, viral and host determinants, measured around acute infection, of HCV clearance. Results The spontaneous viral clearance rate was 33.0% (95% confidence interval (CI) 24.2–42.8). In univariate analyses female sex and fever were significantly associated with spontaneous clearance. The favorable genotypes for rs12979860 (CC) and rs8099917 (TT) were associated with spontaneous clearance, although borderline significant. In multivariate analysis, females with the favorable genotype for rs12979860 (CC) had an increased odds to spontaneously clear HCV infection (adjustedOR 6.62, 95% 2.69–26.13), whereas females with the unfavorable genotype were as likely as men with the favorable and unfavorable genotype to clear HCV. Chronic Hepatitis B infection and absence of HIV coinfection around HCV seroconversion also favor HCV clearance. Conclusions This study shows that co-infection with HIV and HBV and genetic variation in the IL28B region play an important role in spontaneous clearance of HCV. Our findings suggest a possible synergistic interaction between female sex and IL28B in spontaneous clearance of HCV.
Reassessing the relationship between ozone and short-term mortality in U.S. urban communities

Time-series studies that use daily mortality and ambient ozone concentrations exhibit estimates of ozone effects that are variable across cities. We investigate this intercity variability, as well as the sensitivity of the ozone- mortality associations to modeling assumptions and choice of daily ozone metric, based on reanalysis of data from the National Morbidity, Mortality and Air Pollution Study (NMMAPS). Previous work from NMMAPS reported a statistically significant association between ambient 24-h ozone and short-term mortality when averaged across 98 U.S. cities. Separation of ozone health associations from effects due to weather and co-pollutants is central to their interpretation. We examined the sensitivity of city-specific ozone-mortality estimates to adjustments for confounders and effect modifiers, showing substantial sensitivity. We examined ozone-mortality associations in different concentration ranges, finding a larger incremental effect in higher ranges, but also larger uncertainty. Alternative ozone exposure metrics defined by maximum 8-h averages or 1-h maxima show different ozone-mortality associations that cannot be explained by simple scaling relationships. The emphasis in earlier studies based on NMMAPS has been on the reporting of “national” effects, together with prediction intervals that suggest that these national values are precisely estimated. Our view is that ozone-mortality associations, based on time-series epidemiologic analyses of daily data from multiple cities, reveal still-unexplained inconsistencies and show sensitivity to modeling choices and data selection that contribute to serious uncertainties when epidemiological results are used to discern the nature and magnitude of possible ozone-mortality relationships or are applied to risk assessment.
MicroRNA‐221 regulates FAS‐induced fulminant liver failure

Death receptor‐mediated apoptosis of hepatocytes contributes to hepatitis and fulminant liver failure. MicroRNAs (miRNAs), 19‐25 nucleotide‐long noncoding RNAs, have been implicated in the posttranscriptional regulation of the various apoptotic pathways. Here we report that global loss of miRNAs in hepatic cells leads to increased cell death in a model of FAS/CD95 receptor‐induced apoptosis. miRNA profiling of murine liver identified 11 conserved miRNAs, which were up‐regulated in response to FAS‐induced fulminant liver failure. We show that ectopic expression of miR‐221, one of the highly up‐regulated miRNAs in response to apoptosis, protects primary hepatocytes and hepatoma cells from apoptosis. Importantly, in vivo overexpression of miR‐221 by adeno‐associated virus serotype 8 (AAV8) delays FAS‐induced fulminant liver failure in mice. We additionally demonstrate that miR‐221 regulates hepatic expression of p53 up‐regulated modulator of apoptosis (Puma), a well‐known proapoptotic member of the Bcl2 protein family. Conclusion: We identified miR‐221 as a potent posttranscriptional regulator of FAS‐induced apoptosis. miR‐221 may serve as a potential therapeutic target for the treatment of hepatitis and liver failure. (HEPATOLOGY 2011;)
Changes in collagen fibril network organization and proteoglycan distribution in equine articular cartilage during maturation and growth

The aim of this study was to record growth‐related changes in collagen network organization and proteoglycan distribution in intermittently peak‐loaded and continuously lower‐level‐loaded articular cartilage. Cartilage from the proximal phalangeal bone of the equine metacarpophalangeal joint at birth, at 5, 11 and 18 months, and at 6–10 years of age was collected from two sites. Site 1, at the joint margin, is unloaded at slow gaits but is subjected to high‐intensity loading during athletic activity; site 2 is a continuously but less intensively loaded site in the centre of the joint. The degree of collagen parallelism was determined with quantitative polarized light microscopy and the parallelism index for collagen fibrils was computed from the cartilage surface to the osteochondral junction. Concurrent changes in the proteoglycan distribution were quantified with digital densitometry. We found that the parallelism index increased significantly with age (up to 90%). At birth, site 2 exhibited a more organized collagen network than site 1. In adult horses this situation was reversed. The superficial and intermediate zones exhibited the greatest reorganization of collagen. Site 1 had a higher proteoglycan content than site 2 at birth but here too the situation was reversed in adult horses. We conclude that large changes in joint loading during growth and maturation in the period from birth to adulthood profoundly affect the architecture of the collagen network in equine cartilage. In addition, the distribution and content of proteoglycans are modified significantly by altered joint use. Intermittent peak‐loading with shear seems to induce higher collagen parallelism and a lower proteoglycan content in cartilage than more constant weight‐bearing. Therefore, we hypothesize that the formation of mature articular cartilage with a highly parallel collagen network and relatively low proteoglycan content in the peak‐loaded area of a joint is needed to withstand intermittent stress and shear, whereas a constantly weight‐bearing joint area benefits from lower collagen parallelism and a higher proteoglycan content.
Sociodemographic differences in parental satisfaction with an autism spectrum disorder diagnosis†

Abstract Background The diagnostic process for autism spectrum disorder (ASD) can be difficult for families. Growing evidence suggests that the diagnostic process may vary as a function of sociodemographic factors, such as socioeconomic status. The purpose of this study was to extend findings related to families’ experiences obtaining a diagnosis and accessing services for their young child with ASD. Method A mixed methods approach was used in this study, in which 46 families with children with ASD participated. A chi-square analysis compared ratings of parental satisfaction with the diagnostic process and current services between sociodemographic groups, and this was supplemented by thematic analysis of relevant open-ended questions. Results Results indicated that satisfaction ratings varied significantly by maternal education and family income levels. Ratings of satisfaction with the child's paediatrician also differed by family income. Major themes from the open-ended questions are discussed. Conclusions Results support assessing satisfaction and barriers in families seeking healthcare and school-based services to facilitate access to services.
Mastering the Information Age - Solving Problems with Visual Analytics

Data Nodes, Edges Display Interactive Display Visual Analogues VisualItems in ItemRegistry User Figure 6.3: The Information Visualisation Reference Model, adapted from Heer et al.[57] 6.2 State of the Art 93 a visual analytics issue that should be better tackled by all the visualisation communities. Blending different kinds of visualisations in the same application is becoming Blending different kinds of visualisations is currently difficult more frequent. Scientific visualisation and geographic visualisation need information visualisation because they manage multi-valued data with complex topologies that can be visualised using their canonical geometry. In addition, they can also be explored with more abstract visual representations to avoid geometric artefacts. For example, census data can be visualised as a coloured map but also as a multi-dimensional dataset where the longitude and latitude are two attributes among others. Clustering this data by some similarity measure will then reveal places that can be far away in space but behave similarly in term of other attributes (e.g., level of education, level of income, size of houses etc.), similarity that would not be visible on a map. On top of these visualisation systems, a user interface allows control of the overall application. User interfaces are well understood but they can be very different in styles. 3D systems use specific types of interfaces that are very different to traditional desktop interfaces. Moreover, information visualisation systems tend to deeply embed the interaction with the visualisation, offering special kinds of controls either directly inside the visualisations (e.g., range sliders on the axes of parallel coordinates) or around it but with special kinds of widgets (e.g., range sliders for performing range-queries). Interoperability can thus be described at several levels. At the data management level, at the architecture model level and at the interface level. 6.2. 2 Data Management All visual analytics applications start with data that can be either statically collected or dynamically produced. Depending on the nature of the data, visual analytics applications have used various ways of managing their storage. In order of sophistication, they are: Flat files using ad-hoc formats, Structured file formats such as XML, Specialised NoSQL systems, including Cloud Storage, Standard or extended transactional databases (SQL), Workflow or dataflow systems integrating storage, distribution and data processing. We will now consider these data storage methods, paying particular attention to Data Management for visual analytics can rely on different levels of sophistication the levels of service required by visual analytics, such as: Persistence (they all provide it by definition), Typing, Distribution, Atomic transactions, Notification, Interactive performance, Computation.