Miracle-dz/UniFAR-FTUs huggingface dataset:
Presynaptic neurotrophin‐3 increases the number of tectal synapses, vesicle density, and number of docked vesicles in chick embryos

To determine whether presynaptically derived neurotrophins may contribute to synaptic plasticity, we examined whether neurotrophin‐3 (NT‐3) changed the number, size, vesicle content, or vesicle distribution of synapses within the retinorecipient layers of the chick optic tectum. In this system, endogenous NT‐3 derives presynaptically from retinal ganglion cell axons. Retinotectal synapses comprise the majority of synapses in superficial tectal layers, as demonstrated by destruction of retinotectal input by intraocular application of the drug monensin. To examine the effect of increased or decreased levels of NT‐3, either exogenous NT‐3 or monoclonal NT‐3 blocking antibodies were injected into the optic tectum of 19‐day‐old chick embryos, spiked with radiolabeled protein to verify the success of injections and estimate effective concentrations. After 48 hours, the ultrastructure of superficial tectal layers was analyzed and compared with samples from control tecta injected with cytochrome C. NT‐3 increased the number of synapses, synaptic vesicles/profile, synaptic vesicle densities, the number of docked vesicles, and the length of the synaptic profile. Deprivation of anterogradely transported endogenous NT‐3 with NT‐3 antibodies resulted in the opposite effect: decreased numbers of synapses, decreased vesicle densities, and decreased numbers of docked vesicles. Brain‐derived neurotrophic factor (BDNF) had a largely different effect than NT‐3. BDNF increased the density of vesicles and deprivation of endogenous TrkB ligands with TrkB fusion protein reduced the density of vesicles in the synapses, without effects on synapse number or docked vesicles. We conclude that anterogradely transported NT‐3 affects synapse strength in a way that differs from that of presumably postsynaptic‐derived BDNF. J. Comp. Neurol. 458:62–77, 2003. © 2003 Wiley‐Liss, Inc.
TRA‐418, a novel compound having both thromboxane A2 receptor antagonistic and prostaglandin I2 receptor agonistic activities: its antiplatelet effects in human and animal platelets

Summary. TRA‐418 is a novel compound that has been found in our screening for compounds having both thromboxane A2 (TP) receptor antagonistic and prostaglandin I2 (IP) receptor agonistic activities. In the binding assays, TRA‐418 showed a 10‐fold higher affinity to TP‐receptors than IP‐receptors. TRA‐418 inhibited platelet aggregation induced by the TP‐receptor agonist, U‐46619 and by arachidonic acid at concentrations lower than those required for inhibition of ADP‐induced aggregations. Furthermore, TRA‐418 inhibited not only platelet aggregation induced by ADP alone, but also that induced by ADP in the presence of the TP‐receptor antagonist, SQ‐29548. When the IC50 values of TRA‐418 for platelet aggregation were estimated in platelet preparations from monkeys, dogs, cats, and rats using ADP and arachidonic acid as the platelet stimulating agents, it was found that the values estimated in monkey platelets were quite similar to those estimated in human platelets. In ex vivo platelet aggregation in monkeys, TRA‐418 exhibited significant inhibitory effects on arachidonic acid‐induced aggregation in platelet preparations from monkeys treated at 3 µg kg min−1 or higher doses, where neither a significant decrease in blood pressure nor a significant increase in heart rate was observed. These results are consistent with the fact that TRA‐418 has a relatively potent TP‐receptor antagonistic activity together with a relatively weak IP‐receptor agonistic activity.
Antibiotic Dosing in Patients With Acute Kidney Injury

Increasing evidence suggests that antibiotic dosing in critically ill patients with acute kidney injury (AKI) often does not achieve pharmacodynamic goals, and the continued high mortality rate due to infectious causes appears to confirm these findings. Although there are compelling reasons why clinicians should use more aggressive antibiotic dosing, particularly in patients receiving aggressive renal replacement therapies, concerns for toxicity associated with higher doses are real. The presence of multisystem organ failure and polypharmacy predispose these patients to drug toxicity. This article examines the pharmacokinetic and pharmacodynamic consequences of critical illness, AKI, and renal replacement therapy and describes potential solutions to help clinicians give “enough but not too much” in these very complicated patients.
Analysis of Big Data Based On Ensemble Classification

------------------------------------------------------------------- ABSTRACT ---------------------------------------------------- Big Data describes a technology used to store and process the exponentially increasing dataset which contains structured, semi structured and unstructured data that has to be mined for valuable information. It deals with 3 V’s: Volume, Variety and Velocity of processing data. It is associated with cloud computing for the analysis of large data sets in real time. Volume refers to the huge amount of data it collects, Velocity refers to the speed at which it process the data and Variety defines that data does not mean just numbers, dates or strings but also geospatial data,3D data, audio, video, social files, etc. The main objective of the big data technology is to achieve high level quality of data and accessibility for business intelligence. It replaces the traditional warehousing, relational databases and complicates software techniques used to process these huge data’s. The example of big data is petabytes and exabytes . With the rapid development in the networking technology which handles huge data at a time, the big data technology is gaining importance nowadays. It is now rapidly expanding in all science and engineering domains, including physical, biological and biomedical sciences. It is also used in government agencies, financial corporations, large enterprises
Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria.

BACKGROUND & AIMS To explore the hypothesis that selective immune responses to distinct components of the intestinal microflora induce intestinal inflammation, we characterized disease kinetics and bacterial antigen-specific T-cell responses in ex germ-free interleukin 10 -/- and wild-type control mice monoassociated with Enterococcus faecalis , Escherichia coli , or Pseudomonas fluorescens . METHODS Colitis was measured by using blinded histological scores and spontaneous interleukin 12 secretion from colonic strip culture supernatants. Interferon gamma secretion was measured from mesenteric or caudal lymph node CD4 + T cells stimulated with bacterial lysate-pulsed antigen-presenting cells. Luminal bacterial concentrations were measured by culture and quantitative polymerase chain reaction. RESULTS Escherichia coli induced mild cecal inflammation after 3 weeks of monoassociation in interleukin 10 -/- mice. In contrast, Enterococcus faecalis-monoassociated interleukin 10 -/- mice developed distal colitis at 10-12 weeks that was progressively more severe and associated with duodenal inflammation and obstruction by 30 weeks. Neither bacterial strain induced inflammation in wild-type mice, and germ-free and Pseudomonas fluorescens-monoassociated interleukin 10 -/- mice remained disease free. CD4 + T cells from Enterococcus faecalis- or Escherichia coli-monoassociated interleukin 10 -/- mice selectively produced higher levels of interferon gamma and interleukin 4 when stimulated with antigen-presenting cells pulsed with the bacterial species that induced disease; these immune responses preceded the onset of histological inflammation in Enterococcus faecalis -monoassociated mice. Luminal bacterial concentrations did not explain regional differences in inflammation. CONCLUSIONS Different commensal bacterial species selectively initiate immune-mediated intestinal inflammation with distinctly different kinetics and anatomic distribution in the same host.
CCL 2 , CCL 3 and CCL 5 chemokines in systemic sclerosis : the correlation with SSc clinical features and the effect of prostaglandin E 1 treatment

1Division of Rheumatology, Department of BioMedicine, Denothe Center, University of Florence, Florence, Italy; 2Section of Clinical Medicine, Department of Medical Science and Surgery, University of Marche, Ancona, Italy; 3Division of Rheumatology, Department of Internal Medicine and Public Health, University of L’Aquila, L’Aquila, Italy. Francesca Bandinelli, MD, Angela Del Rosso, MD, PhD Armando Gabrielli, MD, PhD, Prof. Roberto Giacomelli, MD, PhD, Prof. Francesca Bartoli, MD Serena Guiducci, MD, PhD Marco Matucci-Cerinic, MD, PhD, Prof. Please address correspondence to: Dr Francesca Bandinelli, Villa Monna Tessa, Division of Rheumatology, Università di Firenze, Viale Pieraccini 18, 50139 Florence, Italy. E-mail: bandin@hotmail.it Received on January 9, 2011; accepted in revised form on December 20, 2011. Clin Exp Rheumatol 2012; 30 (Suppl. 71): S44-S49. © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2012.
Genetic epidemiology of cancer in utah genealogies: A prelude to the molecular genetics of common cancers

The traditional approach of clinical geneticists has been to collect information on families that have come to their attention as unusual clusters of diseased individuals. These efforts have yielded valuable descriptions of traits that were due to simple dominant or recessive genes, but they failed to give insights into complex situations involving age andor sex-dependent penetrance, genetic heterogeneity, multiple loci, and gene-environment interactions. In particular, this approach is ill suited to more common diseases, such as cancer, where many such clusters are expected to occur by chance. Such anecdotal reports are not sufficient to establish the familial clustering of common diseases. The discussion of the familiality of common diseases is therefore only valid when ascertainment of all cases in a well-defined population is complete and the genetic relationships be-tween all the cases are known. These requirements represent the strength of the Utah Database which incorporates genealogical records with a statewide cancer registry. The utilization of these combined data sources allows an unbiased assessment of cancer familiality. In The Utah Database, below, we describe the population, the genealogical database and the Utah Cancer Registry which is the source of the cancer diagnoses. In Familiality of Cancer we review some of the epidemiological findings about cancer in Utah, and our preliminary re-sults of a population-based assessment of clustering. The recognition of familial clustering of common diseases promotes a serious discussion about the appropriate study design to elucidate the disease etiology while emphasizing the mechanisms that could cause clustering. There have been various approaches to the study of clustering, none of which have sought to resolve the disease etiology. For instance, the epidemiologic approach is to determine the risks for relatives
Molecular genetic analysis reveals chromosomal deletion, gene amplification, and autocrine growth factor production in the pathogenesis of human lung cancer.

These studies of lung cancer suggest that a number of molecular mechanisms may be important in the pathogenesis of lung cancer, especially SCLC. An inherited predisposition to develop SCLC may correlate with a nonfunctional, recessive allele for a gene (McKusick #18228, McKusick 1986) that maps to chromosome region 3p(14-23). Individuals at risk would be heterozygous for this allele in their germ line, carrying one copy of a normal functional gene and one mutant, recessive allele. Exposure to carcinogens, in particular cigarette smoke, can produce somatic genetic changes such as chromosomal deletion or gene mutation in the functional allele of this gene, unmasking the nonfunctional allele. Loss of this normal gene may alter the regulation of cell growth, perhaps by allowing the deregulated expression of proto-oncogenes of the myc family, or autocrine growth factors such as GRP and/or its receptor. Alternatively, loss of this gene may result in the cell returning to a less differentiated developmental state where growth regulation is less stringent. Persons with this mutant gene should be at increased risk to develop SCLC, and further RFLP analysis of the 3p region in SCLC may allow identification of specific haplotypes with increased risk of developing lung cancer. If this notion is correct, one might expect to find an increased frequency of second tumors in lung cancer patients and the presence of similar chromosomal deletions in second tumors arising in SCLC patients. In this regard, cured lung cancer patients, including those with SCLC, have a tenfold increased risk of developing a second lung cancer (Fontana 1977; Cortese et al. 1983; Johnson et al. 1986b). In fact, a chromosome 3p deletion along with other chromosomal abnormalities was identified in acute erythroleukemia cells arising in a long-term survivor of SCLC (Bradley et al. 1982), implicating this same region in the pathogenesis of both tumors. Other predictions include the correction of at least a portion of the defect by introducing a normal chromosome 3 into SCLC cells. While c-myc is expressed in many fetal and adult tissues, high-level expression of N- and L-myc is very restricted as to tissue and stage in the developing mouse, with N-myc expressed in the fetal but not adult lung, whereas the lung was the only adult tissue where L-myc expression was detected (Zimmerman et al. 1986). Could these patterns provide a clue to the differential expression of c-, N-, and L-myc found in different lung cancers (Nau et al. 1986)? (ABSTRACT TRUNCATED AT 400 WORDS)
Evaluation of a micro-Doppler classification method on mm-wave data

Radar micro-Doppler signatures (MDS), which show how different parts of the target move, can be utilized for security and safety applications like detection and assessment of human activity at airports, nuclear power plants etc. We have evaluated a MDS classification method on measured data at 77 GHz. The important part of the method is the feature extraction, which is based on selecting the strongest parts of a Cadence-Velocity Diagram (CVD), which expresses how the curves in the MDS repeat. By our classification of MDSs of human gaits we study also how MDSs of more general target types and activities can be distinguished. We have analyzed and improved the method. The method is sound with good classification results but needs further evaluations and improvements.
Perioperative Assessment of Diastolic Dysfunction

Assessment of diastolic function should be a component of a comprehensive perioperative transesophageal echocardiographic examination. Abnormal diastolic function exists in >50% of patients presenting for cardiac and high-risk noncardiac surgery, and has been shown to be an independent predictor of adverse postoperative outcome. Normalcy of systolic function in 50% of patients with congestive heart failure implicates diastolic dysfunction as the probable etiology. Comprehensive evaluation of diastolic function requires the use of various, load-dependent Doppler techniques This is further complicated by the additional effects of dehydration and anesthetic drugs on myocardial relaxation and compliance as assessed by these Doppler measures. The availability of more sophisticated Doppler techniques, e.g., Doppler tissue imaging and flow propagation velocity, makes it possible to interrogate left ventricular diastolic function with greater precision, analyze specific stages of diastole, and to differentiate abnormalities of relaxation from compliance. Additionally, various Doppler-derived ratios can be used to estimate left ventricular filling pressures. The varying hemodynamic environment of the operating room mandates modification of the diagnostic algorithms used for ambulatory cardiac patients when left ventricular diastolic function is evaluated with transesophageal echocardiography in anesthetized surgical patients.
Hypotension begins at 110 mm Hg: redefining "hypotension" with data.

BACKGROUND Clinicians routinely refer to hypotension as a systolic blood pressure (SBP) < or =90 mm Hg. However, few data exist to support the rigid adherence to this arbitrary cutoff. We hypothesized that the physiologic hypoperfusion and mortality outcomes classically associated with hypotension were manifest at higher SBPs. METHODS A total of 870,634 patient records from the National Trauma Data Bank with emergency department SBP and mortality data were analyzed. Patients (140,898) with severe head injuries, a Glasgow Coma Score < or =8, and base deficit (BD) <5, or missing data items were excluded from analysis. Admission BD, as a measure of metabolic hypoperfusion, was evaluated in 81,134 patients and mortality was plotted against SBP. RESULTS Baseline mortality was <2.5%. However, at 110 mm Hg, the slope of the mortality curve increased such that mortality was 4.8% greater for every 10-mm Hg decrement in SBP. This effect was consistent to a maximum of 26% mortality at a SBP of 60 mm Hg. Hypoperfusion (change in the slope of BD curve) began to increase above baseline of 4.5 at a SBP 118 mm Hg. CONCLUSION Taking the BD and mortality measurements together, this analysis shows that a SBP < or =110 mm Hg is a more clinically relevant definition of hypotension and hypoperfusion than is 90 mm Hg. This analysis will also be useful for developing appropriately powered studies of hemorrhagic shock.
Utility of the Canadian Occupational Performance Measure as an admission and outcome measure in interdisciplinary community-based geriatric rehabilitation

Abstract In a community-based geriatric rehabilitation project, the Canadian Occupational Performance Measure (COPM) was used to develop a coordinated, interdisciplinary, and client-centred approach focusing on occupational performance. The purpose of this study was to evaluate the utility of the COPM as an admission and outcome measure in an interdisciplinary geriatric rehabilitation context in Denmark. Eighteen occupational and physiotherapists administered the COPM among elderly citizens. Of 185 citizens referred to the study, 152 were admitted to rehabilitation based on health indices, and 124 completed the COPM after their admission, identifying 404 occupational performance issues in all. Post-assessment data were obtained from 95 participants and revealed statistically significant positive change (p < 0.001) in both performance and satisfaction with performance. Furthermore the therapists answered a questionnaire evaluating their experiences, showing that they found development in knowledge and community between the professions to benefit both therapists and citizens, and gained a better insight into their clients' everyday lives through the COPM. In conclusion, the COPM may be useful as an admission and outcome measurement for the rehabilitation of elderly citizens; however, aspects of education and administration must be considered before the instrument can be successfully administered in an interdisciplinary geriatric rehabilitation context.
Adaptive Non-Linear Prediction of Speech in Impulse Noise

This paper investigates the Linear Predictive Coding (LPC) of speech in an impulsive noise environment. Batch processing and adaptive processing are comparatively studied and it is shown that the adaptive processing scheme is basically suitable in an impulsive noise environment. As an extended version of the Order Statistic Least Mean Square (OSLMS) algorithm addressed by Shimamura et al., an OSLMS algorithm involving ambiguous sorting is developed. The performance of the proposed algorithm is demonstrated and it is shown that the convergence speed of the proposed algorithm is similar with that of the LMS algorithm, while the effects of impulse noise are significantly suppressed by the proposed algorithm.
Recurrent lacunar infarction following a previous lacunar stroke: a clinical study of 122 patients

Objective: To determine clinical variables related to recurrent lacunar infarction following a previous lacunar stroke. Methods: A total of 122 out of 733 consecutive patients with lacunar infarction collected from a hospital based registry between 1986 and 2004 were readmitted because of a recurrent lacunar infarction. In a subset of 59 patients, cognition was assessed using the Mini-Mental State Examination (MMSE). Predictors of lacunar infarction recurrence were assessed by logistic regression analysis. Results: First lacunar infarction recurrence occurred in 101 patients (83%) and multiple recurrences in 21. The mean time between first ever lacunar infarction and recurrent lacunes was 58.3 months (range 2–240). In the subset of 59 patients in whom cognition was studied, cognitive impairment, defined as an MMSE score <24, was detected in 16% (8/49) of patients with first lacunar infarction recurrence and in 40% (4/10) of those with multiple lacunar infarction recurrences. In the multivariate analysis, hypertension (odds ratio 2.01, 95% CI 1.23 to 3.30) and diabetes (odds ratio 1.62, 95% CI 1.07 to 2.46) were significant predictors of lacunar stroke recurrence, whereas hyperlipidaemia was inversely associated (odds ratio 0.52, 95% CI 0.30 to 0.90). Conclusions: Hypertension and diabetes were significant factors related to recurrent lacunar infarction. Hyperlipidaemia appeared to have a protective role. Cognitive impairment was a frequent finding in patients with multiple lacunar infarction recurrences.
Local acquisition and nosocomial transmission of Klebsiella pneumoniae harbouring the blaNDM‐1 gene in Australia

Patient A, a 68-year-old Australian-born woman living with her husband and son, had never travelled overseas and had no known contact with overseas visitors. Her past history included chronic bilateral lymphoedema with recurrent lower limb cellulitis, requiring multiple previous hospital admissions and home nursing care. She presented with septic shock and right leg erythema surrounding a 10 10 cm ulcer near the right lateral malleolus. Magnetic resonance imaging showed bony oedema and enhancement in the lateral malleolus, suggestive of osteomyelitis. Pseudomonas aeruginosa was isolated from blood cultures. A tissue biopsy from the overlying ulcer cultured P. aeruginosa, non-multiresistant methicillinresistant Staphylococcus aureus (NORSA), and carbapenemresistant Klebsiella pneumoniae, resistant to all first-line antimicrobials tested and susceptible to only colistin and fosfomycin.