Miracle-dz/UniFAR-FTUs huggingface dataset:
Pooled analysis of prognostic impact of uPA and PAI-1 in breast cancer patients

Summary In this report we present an extension of the pooled analysis of the prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in breast cancer patients. We analyzed a different endpoint, metastasis-free survival (MFS). We checked the consistency of the estimates for uPA and PAI-1 for relapse-free survival (RFS) and MFS exploring possible sources of heterogeneity. Nodal status, the most important prognostic factor for breast cancer, introduced heterogeneity in the uPA/PAI-1 survival analyses, reflecting the interaction between nodal status and uPA/PAI-1. The estimates for uPA and PAI-1 were found to be consistent, even when a different transformation of their values was used. The heterogeneity of the separate data sets decreased if the levels of uPA and PAI-1 were ranked, data sets were pooled, and the analyses corrected for the base model that included all traditional prognostic factors, and stratified by data set. We conclude that uPA and PAI-1 are ready to be used in the clinic to help classify breast cancer patients into high and low risk groups. Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.
Gynecological efficacy and chemical investigation of Vitex agnus-castus L. fruits growing in Egypt

Flavonoid glycosides, orientin and apigenin 3, 8-di-C-glycosides in addition to, iridoid compound, aucubin were isolated from the ethanolic extract of Vitex agnus-castus fruits. Their structures were identified on the basis of the spectroscopic data. The estrogenic activity of the ethanolic extract in two dose levels 0.6 and 1.2 g kg−1 per body weight (b.w.) was studied by the vaginal smear, and uterine weight methods for normal and ovariectomized female rats. The extract induced significant increase in the uterine weight of ovariectomized rats at two dose levels comparable to that of control group. The percentages of the total average number of scores were increased significantly too. Significant increases in plasma progesterone and total estrogens levels were shown at the two dose levels when compared to that of control group. On the other side, the extract induced significant reduction in lutinizing and plasma prolactin hormones.
Electrophysiological markers of voice familiarity

Our ability to discriminate and recognize human voices is amongst the most important functions of the human auditory system. The current study sought to determine whether electrophysiological markers could be used as objective measures of voice familiarity, by looking at the electrophysiological responses [mismatch negativity (MMN) and P3a] when the infrequent stimulus presented is a familiar voice as opposed to an unfamiliar voice. Results indicate that the MMN elicited by a familiar voice is greater than that elicited by an unfamiliar voice at FCz. The familiar voice also produced a greater P3a wave than that triggered by the unfamiliar voice at Fz. As both the MMN and the P3a were elicited as participants were instructed not to pay attention to incoming stimulation, these findings suggest that voice recognition is a particularly potent preattentive process whose neural representations can be objectively described through electrophysiological assessments.
Analytical and clinical evaluation of the new Fujirebio Lumipulse®G non-competitive assay for 25(OH)-vitamin D and three immunoassays for 25(OH)D in healthy subjects, osteoporotic patients, third trimester pregnant women, healthy African subjects, hemodialyzed and intensive care patients

Abstract Background: In this study, we provide a short analytical evaluation of the new Fujirebio Lumipulse®G non-competitive immunoassay for 25(OH)D. Clinical performance was compared with three commercial competitive automated immunoassays against a Vitamin D Standardization Program (VDSP)-traceable liquid chromatography-tandem mass spectrometry (LC-MS/MS) in six different clinically relevant populations. Methods: Lumipulse®G 25(OH)D precision, measurement uncertainty, recovery, limit of quantification were assessed, as well as 25(OH)D2 and C3-epimer recovery. For method comparison, 250 serum samples obtained in healthy Caucasians and Africans, osteoporotic, hemodialyzed and intensive care patients and 3rd trimester pregnant women were analyzed by all methods. Correlation was studied using Passing-Bablok and Bland-Altman analysis. Concordance correlation coefficient (CCC) was calculated to evaluate agreement between immunoassays and the LC-MS/MS. Results: The Lumipulse®G 25(OH)D assay presented interesting analytical features and showed excellent correlation to the LC-MS/MS results (y=1.00×–1.35 ng/mL), as obtained in healthy Caucasian individuals. In the other special populations, Lumipulse®G presented a concordance with LC-MS/MS which was generally higher than competitors, even if all methods significantly under-recovered 25(OH)D in hemodialyzed patients. Intra-assay CV ranged from 12.1% at 9.6 ng/mL to 2.1% at 103.7 ng/mL and inter-assay CV ranged from 16.2 to 3.7% at the same concentrations, respectively. Measurement uncertainty, with a probability of 95%, were respectively 33.1 and 7.6% at these concentrations. LOQ was found to be at 4.6 ng/mL. Mean (95% CI) 25(OH)D2 revovery was 77% (74–81) and no cross-reactivity was observed with C3-epimer. Conclusions: Fujirebio Lumipulse®G 25-OH Vitamin D Total assay is therefore considered suitable for assessment of vitamin D status in clinical routine.
Assessment of practical knowledge of self-management of acute asthma.

AIMS To develop an instrument for the measurement of, and to determine the level of, practical knowledge of self-management of acute asthma. METHODS Eighty patients with moderate/severe asthma attending a hospital-based asthma clinic responded to an interviewer-administered questionnaire. Subjects were asked to describe the action they would take in response to each of two hypothetical evolving attacks: (1) one of gradually increasing severity and (2) the other developing rapidly. Responses were scored according to the appropriateness of actions taken relevant to the stage of the attack. Transcripts of the responses were scored independently by three of the investigators according to a system based on Thoracic Society of Australia and New Zealand (TSANZ) and British Thoracic Society (BTS) consensus statements on asthma management. A 25-point scale was used on which 0 represented a total lack of appropriate responses and a score of 25 was an optimal response. RESULTS Interrater and intrarater reliability were excellent. Mean (+/- SD) scores for the slow and rapid onset attacks were 12.8 +/- 4.0 and 13.9 +/- 4.8, respectively. The scores for the two scenarios were predicted by each other (p = 0.002) and by the interviewer's rating of asthma management knowledge (p = 0.0004, p = 0.0001), but not by age, sex, race, previous asthma morbidity, depression, or anxiety. In both scenarios, most patients indicated that they would increase inhaled beta-agonist (85% for slow-onset scenarios and 94% for rapid-onset scenarios, respectively) and use their action plan and/or seek urgent medical advice at an appropriate time (74% and 70%). Although some would measure peak expiratory flow (PEF) initially (54% and 30%), only a minority would continue to monitor PEF in the context of worsening acute asthma (30% and 24%). When a severe life-threatening situation was described, only 50% and 64%, respectively, indicated that they would call emergency services. CONCLUSIONS Scenarios describing hypothetical asthma attacks are a useful and reproducible method of assessing practical knowledge of self-management of acute asthma. Patients presented with scenarios frequently made errors in their hypothetical responses. The errors made with scenarios, which parallel errors reported in real clinical situations, occurred despite the fact that this patient population had received considerable education and training about how to manage asthma. Most indicated they would not monitor PEF even in an exacerbation of asthma and would not call emergency services despite life-threatening asthma. These scenarios may allow us to explore the gap between knowledge about treatment and actual practice, and perhaps to help close that gap and thus reduce asthma morbidity and mortality.
Lung collagen composition and synthesis. Characterization and changes with age.

Abstract In the lung, collagen is found associated with bronchi, with blood vessels, and with the alveolar interstitium; it is known to be fundamental in the maintenance of lung structure and function. Two collagen chains, α1 and α2, can be extracted from rabbit lung homogenates; each chain has an approximate molecular weight of 100,000 and is composed of amino acids that are characteristic of collagen, but are not specific for lung. Lung slices incubated in vitro synthesize α1 and α2 chains, as demonstrated by carboxymethylcellulose chromatography, by sodium dodecyl sulfate acrylamide gel electrophoresis, by acidic acrylamide gel electrophoresis, by sensitivity to collagenase, and by sensitivity to trichloroacetic acid at 90°. As a percentage of dry weight, lung protein does not change significantly during maturation, but the content of collagen increases 5-fold from the late stages of gestation to adult life. The average rate of collagen synthesis per cell decreases slowly 10-fold from fetal to adult life whereas the average rate of noncollagen protein synthesis per cell rapidly decreases to adult levels before birth. The rate of collagen synthesis relative to the rate of total protein synthesis is low in fetal life, rises from 2 to 15% in the first month of life, and then declines by 2 months of age to the fetal level throughout adult life. The maturing lung, therefore, has significant changes in genetic expression during a period of rapid growth as the lung converts to a gas-exchanging organ.
Bacteriological studies of developing supragingival dental plaque.

The predominant flora of plaque developing on an area of about 1 sq cm. on the middle third of the buccal surface of the upper first molar of one individual was studied. Samples were taken at 5 and 15 min, 1, 2, 4 and 8 hr, and 1, 2, 4, 8 and 16 days; the tooth surface was cleaned prior to each period. Plaque samples were handled and cultured under anaerobic conditions utilizing various growth media. AH isolates from blood agar plates in Brewer jars with 30 to 100 colonies were characterized. Streptococcus sanguis, the single-most predominant organism, and Actinomyces viscosus were consistently found. Streptococcus mitis, Staphylococcus epidermidis, Actinomyces israelii, Peptostreptococcus sp. and Veillonella alcalescens were found at more than one time period. High proportions of “suspected pairs” (mixtures of 2 or more intimately-associated organisms), were regularly detected. Bacterial population changes with time were observed. Many isolates, particularly those present in plaques up to 8 hr, agglutinated in the presence of saliva. Less than half of the isolates, including Gram-positive saccharolytic rods, staphylococci and some S. sanguis strains, formed plaque in vitro on wires in the presence of sucrose or glucose. The data suggest that the nature of the early microflora observed is determined by bacterial attachment which may be influenced by, amongst others, salivary constituents. Subsequent cell multiplication leads to a large bacterial increase in which proportional changes may occur as a result of differences in bacterial growth.
Running increases neurogenesis without retinoic acid receptor activation in the adult mouse dentate gyrus

Both vitamin A deficiency and high doses of retinoids can result in learning and memory impairments, depression as well as decreases in cell proliferation, neurogenesis and cell survival. Physical activity enhances hippocampal neurogenesis and can also exert an antidepressant effect. Here we elucidate a putative link between running, retinoid signaling, and neurogenesis in hippocampus. Adult transgenic reporter mice designed to detect ligand‐activated retinoic acid receptors (RAR) or retinoid X receptors (RXR) were used to localize the distribution of activated RAR or RXR at the single‐cell level in the brain. Two months of voluntary wheel‐running induced an increase in hippocampal neurogenesis as indicated by an almost two‐fold increase in doublecortin‐immunoreactive cells. Running activity was correlated with neurogenesis. Under basal conditions a distinct pattern of RAR‐activated cells was detected in the granule cell layer of the dentate gyrus (DG), thalamus, and cerebral cortex layers 3–4 and to a lesser extent in hippocampal pyramidal cell layers CA1–CA3. Running did not change the number of RAR‐activated cells in the DG. There was no correlation between running and RAR activation or between RAR activation and neurogenesis in the DG of hippocampus. Only a few scattered activated retinoid X receptors were found in the DG under basal conditions and after wheel‐running, but RXR was detected in other areas such as in the hilus region of hippocampus and in layer VI of cortex cerebri. RAR agonists affect mood in humans and reduce neurogenesis, learning and memory in animal models. In our study, long‐term running increased neurogenesis but did not alter RAR ligand activation in the DG in individually housed mice. Thus, our data suggest that the effects of exercise on neurogenesis and other plasticity changes in the hippocampal formation are mediated by mechanisms that do not involve retinoid receptor activation. © 2008 Wiley‐Liss, Inc.
Chromatin condensation and acrosome development during spermiogenesis of Ensis ensis (Mollusca, Bivalvia)

We describe chromatin condensation and acrosome development during spermiogenesis of Ensis ensis. The overall shape of the mature spermatozoon corresponds to the primitive type. The nucleus is oval and on its superior pole there is an elongated acrosome; the middle piece contains four mitochondria around the centriolar complex. The condensation of the nuclei seems to occur in three steps: first the diameter of chromatin fibers increases slightly from 17 to 20 nm; second, in midspermatids fiber pairs coalesce; and third, the coalescence continues by addition of other fibers until the nuclei become highly compacted. Chromatin changes are related with nuclear protein composition. Small proacrosomal vesicles show two regions of different electron density. At a later stage they fuse to give a single, spherical vesicle in round spermatids, which migrates to the upper pole and transforms into a tapered acrosome (18 μm long) with a central channel filled with finely fibrous material. © 1994 Wiley‐Liss, Inc.
Prevalence of sleep bruxism and associated factors in preschool children.

PURPOSE The purpose of this study was to evaluate the prevalence of sleep bruxism and associated factors in three- to five-year-olds. METHODS A representative cross-sectional study was conducted with a sample of 749 preschool children during immunization campaigns. Data acquisition involved an oral clinical exam, anthropometric measures, and a questionnaire administered in interview form. All data were analyzed using the chi-square test and Poisson regression with robust variance with the aid of SPSS software. RESULTS The prevalence of sleep bruxism among preschool children was approximately 14 percent. Statistically significant associations were found: between sleep bruxism and lower dental crowding (prevalence ratio=3.38; 95% confidence interval=1.9-5.7); for the habit of biting on objects (PR=2.49; 95% CI=1.4-4.4); for duration of breast-feeding for a period longer than 12 months (PR=1.98; 95% CI=1.2-3.2); and for bottle-feeding for more than 24 months (PR=1.93; 95% CI=1.2-3.1). CONCLUSIONS Lower arch crowding, the habit of biting on objects, and prolonged breast-feeding and bottle-feeding were associated with sleep bruxism in the preschool children analyzed in the present study.
Towards Collaborative Development Based on Software Architecture

Software projects often require many software engineers to coordinate their efforts to build large software systems. How to support collaborative development among the stakeholders in a project, even if separated by time or space, to produce software artifacts efficiently becomes a very important problem. Software architectures are considered important because they are the blueprints for target software products and determine system-wide qualities, and they can be used to organize various software artifacts in software development process from a high level perspective. Based on such an important role of software architectures, this paper puts forward an approach to collaborative software development based on software architecture, to support the collaboration spanning the whole software lifecycle. Moreover, the paper provides the detail on how this method works efficiently by a case study.
A systematic review of metabolic side effects related to the use of antipsychotic drugs in dementia

ABSTRACT Background: In clinical practice, Second Generation Antipsychotics (SGAs) are often used as first-line treatment for the Behavioral and Psychological Symptoms of Dementia (BPSD) in older adults due to their fewer neurological adverse events and similar effectiveness compared with First Generation Antipsychotics (FGAs). SGAs, however, are associated with more severe metabolic side effects (weight gain, hyperglycemia, diabetes risk, and hyperlipidemia) than FGAs are. In general, older patients, especially those affected by dementia, are at increased risk for malnutrition, and tend to have lower basal metabolism and reduced liver and kidney function. However, little is known about the metabolic side effects of antipsychotic drugs in this population. Methods: A comprehensive review of the literature published between January 1996 and December 2012 investigating the metabolic side effects related to FGAs and SGAs use in old patients affected by dementia. Results: Antipsychotic drugs currently used to treat BPSD in subjects with mild to moderate dementia are associated with weight gain. Currently, there are insufficient data to support a causal relationship between the use of FGAs and SGAs and changes in glucose homeostasis or lipid metabolism in older persons affected by severe dementia (MMSE <14). Conclusion: A possible association between antipsychotic drugs use and weight gain might exist, in particular in subjects with mild to moderate dementia whereas no significant effects are demonstrated regarding glucose homeostasis and lipid metabolism. The antipsychotic drugs potential for causing metabolic abnormalities in older patients requires further specifically designed studies. Clinicians must be aware of this possibility even if the shorter periods of treatment administered in late-life might not be as harmful as it is in younger individuals.
Rheumatoid disease and the heart: from epidemiology to echocardiography

Rheumatoid disease (RD) is a common chronic inflammatory condition associated with progressive joint destruction. Sufferers of RD experience reduced life expectancy, reflected in the increased standardised mortality rates reported in several studies over the last 50 years. Most studies indicate that the increased mortality affecting this population is mainly due to cardio-vascular disease. Epidemiological data have revealed an increased risk of developing ischaemic heart disease and heart failure in RD. The increased risk of ischaemic heart disease may result from traditional risk factors but data suggest that RD may confer risk independently. Although pericardial involvement, valvopathy and myocarditis are the most well-recognised cardiac manifestations of RD, and constitute a rheumatoid heart disease, these features are relatively benign. The current prevalence of rheumatoid heart disease in the era of early administration of disease-modifying therapy requires evaluation.
Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis

Myelin-directed autoimmunity is considered to play a key role in the pathogenesis of multiple sclerosis (MS). Increased production of both pro- and anti-inflammatory cytokines is a common finding in MS. Interleukin-17 (IL-17) is a recently described cytokine produced in humans almost exclusively by activated memory T cells, which can induce the production of proinflammatory cytokines and chemokines from parenchymal cells and macrophages. In situ hybridisation with synthetic oligonucleotide probes was adopted to detect and enumerate IL-17 mRNA expressing mononuclear cells (MNC) in blood and cerebrospinal fluid (CSF) from patients with MS and control individuals. Numbers of IL-17 mRNA expressing blood MNC were higher in patients with MS and acute aseptic meningoencephalitis (AM) compared to healthy individuals. Higher numbers of IL-17 mRNA expressing blood MNC were detected in MS patients examined during clinical exacerbation compared to remission. Patients with MS had higher numbers of IL-17 mRNA expressing MNC in CSF compared to blood. This increase in numbers of IL-17 mRNA expressing MNC in CSF was not observed in patients with AM. Our results thus demonstrate increased numbers of IL-17 mRNA expressing MNC in MS with higher numbers in CSF than blood, and with the highest numbers in blood during clinical exacerbations.
Stroke Incidence in Women under 60 Years of Age Related to Alcohol Intake and Smoking Habit

Background and Purpose: The association between alcohol intake, cigarette smoking and risk of stroke amongst women remains unclear, especially in young women. Methods: This prospective cohort study included 45,449 Swedish women aged 30–50 years free of stroke and heart diseases at enrolment in 1991 and 1992. Information on drinking and smoking habits at enrolment was collected using a questionnaire. Incident stroke cases were identified through cross-linkage to the Swedish Inpatient Register. Cox proportional hazards regression models were used to calculate relative risks (RR) and their corresponding 95% confidence intervals (CIs). Results: During an average of 11 years of follow-up, 170 incident stroke cases, of which 111 ischemic and 47 hemorrhagic, were identified. Compared to abstainers, risk of stroke was reduced among women consuming less than 20 g (RR = 0.7, 95% CI 0.5–1.0) or 20–69.9 g (RR = 0.5, 95% CI 0.3–0.7) of alcohol per week, whilst women who consumed ≧70 g of alcohol per week had a nonsignificant reduced relative risk (RR = 0.7, 95% CI 0.4–1.3). We found no difference in stroke risk according to the types of alcoholic beverage consumed. Compared with never smokers, there was an increased risk of all strokes among current smokers of 1–9 cigarettes/day (RR = 2.3, 95% CI 1.5–3.7) or ≧10 cigarettes/day (RR = 2.6, 95% CI 1.7–4.1). The observed smoking-related excess risks were confined mainly to ischemic stroke. Former smokers had a 50–60% increase in RRs of both ischemic and hemorrhagic stroke. In stratified analyses, current smokers had a 4-fold excess risk if they were nondrinkers (RR = 4.2; 95% CI 2.2–7.8) but a lower risk (RR = 1.5; 95% CI 0.8–2.4) if they drank in moderation. Compared to never drinkers and never smokers, women who drank in moderation were also at reduced risk (RR = 0.6; 95% CI 0.3–1.1). These interactions were statistically significant (p = 0.001). Conclusions: Light to moderate alcohol intake, regardless of type of alcoholic beverage, reduces risk of stroke among women under 60 years of age, in particular those women who were never smokers. Smoking increases the risk of stroke, especially ischemic stroke.