Miracle-dz/UniFAR-FTUs huggingface dataset:
Pre- and In-Hospital Delays From Stroke Onset to Intra-arterial Thrombolysis

Background and Purpose— Thrombolysis for treatment of acute ischemic stroke should be administered as fast as possible after symptom onset. The aim of this study was to examine, in our tertiary care center, the time intervals preceding intra-arterial thrombolysis in order to accelerate and optimize the management of acute strokes. Methods— Between January 1, 2000, and April 30, 2002, 597 patients with acute stroke were admitted to our stroke center. One hundred forty-eight patients underwent diagnostic arteriography, and 100 (16.8%) received intra-arterial thrombolysis. For all patients, we prospectively recorded and analyzed the time of symptom onset, admission, CT and/or MRI scan, diagnostic arteriography, and, if performed, intra-arterial thrombolysis. Results— The mean time to arrival in the emergency department was 99 minutes for patients who were admitted directly (Bern patients), 127 minutes for those who were referred from community hospitals without a CT scanner (non-Bern/−CT patients), and 210 minutes for patients from hospitals with imaging facilities (non-Bern/+CT patients). The mean delay from symptom onset to treatment was 234 minutes for Bern patients, 269 minutes for non-Bern/−CT patients, and 302 minutes for non-Bern/+CT patients. The patients from the last group needed longer to receive intra-arterial thrombolysis than did patients who were admitted directly (P =0.002) or who were transferred from a hospital without a CT scanner (P =0.03). Conclusions— This prospective study indicates that direct referral without prior imaging at community hospitals shortens the time until intra-arterial thrombolysis. In addition, our in-hospital delay preceding intra-arterial thrombolysis is longer than the delays reported for intravenous thrombolysis and indicates potential for improvement.
Systemically Administered Ligands of Toll-Like Receptor 2, -4, and -9 Induce Distinct Inflammatory Responses in the Murine Lung

Objective. To determine whether systemically administered TLR ligands differentially modulate pulmonary inflammation. Methods. Equipotent doses of LPS (20 mg/kg), CpG-ODN (1668-thioat 1 nmol/g), or LTA (15 mg/kg) were determined via TNF activity assay. C57BL/6 mice were challenged intraperitoneally. Pulmonary NFκB activation (2 h) and gene expression/activity of key inflammatory mediators (4 h) were monitored. Results. All TLR ligands induced NFκB. LPS increased the expression of TLR2, 6, and the cytokines IL-1αβ, TNF-α, IL-6, and IL-12p35/p40, CpG-ODN raised TLR6, TNF-α, and IL12p40. LTA had no effect. Additionally, LPS increased the chemokines MIP-1α/β, MIP-2, TCA-3, eotaxin, and IP-10, while CpG-ODN and LTA did not. Myeloperoxidase activity was highest after LPS stimulation. MMP1, 3, 8, and 9 were upregulated by LPS, MMP2, 8 by CpG-ODN and MMP2 and 9 by LTA. TIMPs were induced only by LPS. MMP-2/-9 induction correlated with their zymographic activities. Conclusion. Pulmonary susceptibility to systemic inflammation was highest after LPS, intermediate after CpG-ODN, and lowest after LTA challenge.
Cytochrome P450 expression in human hepatocytes and hepatoma cell lines: molecular mechanisms that determine lower expression in cultured cells

1. Cultured hepatic cells have reduced cytochrome P450 (CYP) activities in comparison with human liver, but the mechanism(s) that underlies this circumstance is not clear. We investigated the causes of this low CYP activity by analysing the activity, protein, mRNA and heterologous nuclear RNA contents of the most important CYPs involved in drug metabolism (1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4, 3A5) in cultured human hepatocytes, and in HepG2 and Mz-Hep-1 hepatoma cell lines. 2. After 24 h of culture, hepatocytes retained most of their CYP activities and protein contents, but the mRNA decreased 20-fold. However, the mRNA content of most CYPs in 24-h hepatocytes was still 400-fold higher than in hepatoma cells. When we examined the transcriptional activity of the CYP genes, this decreased during culture time in hepatocytes and it was poor in hepatoma cell lines. 3. We investigated the abundance of key hepatic transcription factors that govern CYP transcription (C/EBP- β : LAP and LIP, HNF-3 α, HNF-4 α, RXR- α) and observed that the expression of some factors was altered in the hepatoma cells. 4. In conclusion, the loss of biotransformation activity in cultured hepatic cells is caused by a decrease in CYP transcription, which correlates with an alteration in the expression of key transcription factors.
Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infectionsa

Benjamin A. Lipsky, Anthony R. Berendt, Paul B. Cornia, James C. Pile, Edgar J. G. Peters, David G. Armstrong, H. Gunner Deery, John M. Embil, Warren S. Joseph, Adolf W. Karchmer, Michael S. Pinzur, and Eric Senneville Department of Medicine, University of Washington, Veterans Affairs Puget Sound Health Care System, Seattle; Bone Infection Unit, Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Trust, Oxford; Department of Medicine, University of Washington, Veteran Affairs Puget Sound Health Care System, Seattle; Divisions of Hospital Medicine and Infectious Diseases, MetroHealth Medical Center, Cleveland, Ohio; Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands; Southern Arizona Limb Salvage Alliance, Department of Surgery, University of Arizona, Tucson; Northern Michigan Infectious Diseases, Petoskey; Department of Medicine, University of Manitoba, Winnipeg, Canada; Division of Podiatric Surgery, Department of Surgery, Roxborough Memorial Hospital, Philadelphia, Pennsylvania; Department of Medicine, Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Orthopaedic Surgery and Rehabilitation, Loyola University Medical Center, Maywood, Illinois; and Department of Infectious Diseases, Dron Hospital, Tourcoing, France
Overexpression of miR-155 promotes the proliferation and invasion of oral squamous carcinoma cells by regulating BCL6/cyclin D2

Although microRNA-155 (miR-155) is known to play an important role in many cancers, its expression and function in oral squamous cell carcinoma (OSCC) was not fully understood. Thus, in the present study, we investigated the expression of miR-155 and also the role this miR plays in OSCC. We used the OSCC cell line (CAL27) and paired tumor and non-tumor tissue samples from patients with OSCC in order to detect the expression of miR-155. Cell proliferation, migration and invasion assays were then undertaken in order to determine the effect of miR-155 on the biological behavior of CAL27 cells following transient transfection with miR-155 mimic and antagomir. The regulatory effect of miR-155 on its target gene B-cell CLL/lymphoma 6 (BCL6) and downstream gene cyclin D2 (CCND2) was also analyzed. We found that miR-155 expression in OSCC cell and tumor tissues was significantly higher than that of the controls. We noted that the miR-155 mimic enhanced CAL27 cell proliferation, migration and invasion ability, downregulated BCL6 levels, and increased cyclin D2 expression. However, we noted that abrogating miR-155 with the miR-155 antagomir suppressed CAL27 cell proliferation, migration and invasion, upregulated BCL6 and reduced cyclin D2 expression. These results indicate that miR-155 plays a tumor-promoting role in OSCC by regulating the BCL6/cyclin D2 axis.
Gender-Job Satisfaction Differences Across Europe: An Indicator for Labor Market Modernization

In 14 member states of the European Union, women's relative to men's levels of job satisfaction are compared by using data of the European Household Community Panel. The countries under consideration can be assigned to three different groups. Denmark, Finland and the Netherlands do not show significant gender-job satisfaction differences. In contrast, in Portugal men are more satisfied with their jobs than women. However, in the vast majority of the investigated countries female workers show a significantly higher level of job satisfaction. As the majority of women are disadvantaged compared to men in the labor market, the findings clearly demonstrate a gender-job satisfaction paradox in these countries. From this point of view, only Denmark, Finland and the Netherlands display gender-job satisfaction equality. The results suggest that objective (socio-economic and institutional) determinants of labor market statuses and subjective (assessed and evaluated) perspectives are mutually complementary. The more restrictive the labor market access and process is for women, the more likely a gender-job satisfaction paradox is to emerge in any country. With regard to the process of labor market modernization, the results support the hypotheses that equal opportunities for women and men like in Scandinavian countries and also partially in the Netherlands implicate that the gender-job satisfaction paradox does not appear anymore due to a fading-out over past decades.
Learning Networks of Stochastic Differential Equations

We consider linear models for stochastic dynamics. To any such model can be associated a network (namely a directed graph) describing which degrees of freedom interact under the dynamics. We tackle the problem of learning such a network from observation of the system trajectory over a time interval $T$. We analyze the $\ell_1$-regularized least squares algorithm and, in the setting in which the underlying network is sparse, we prove performance guarantees that are \emph{uniform in the sampling rate} as long as this is sufficiently high. This result substantiates the notion of a well defined `time complexity' for the network inference problem.
An experimental and numerical investigation of the interaction between splits and edge delaminations in [+20m/-20m]ns carbon/epoxy laminates

Experimental and numerical investigations were carried out to study ply thickness scaling effects of angle ply laminates and interaction between splits and edge delaminations. Two series of [+20m/-20m]ns laminates which are dispersed ply laminates (m=1, n=8) and blocked ply laminates (m=2, n=4) were tested under uniaxial tensile load. Additionally, interrupted tests were carried out to investigate the failure initiation mechanism. A FE method using the explicit code LS-Dyna with splitting and interface elements was applied to understand the failure process. Moreover, a simplified method was also used to predict the stress for the angle ply edge delamination initiation.
Improving false discovery rate estimation

MOTIVATION Recent attempts to account for multiple testing in the analysis of microarray data have focused on controlling the false discovery rate (FDR). However, rigorous control of the FDR at a preselected level is often impractical. Consequently, it has been suggested to use the q-value as an estimate of the proportion of false discoveries among a set of significant findings. However, such an interpretation of the q-value may be unwarranted considering that the q-value is based on an unstable estimator of the positive FDR (pFDR). Another method proposes estimating the FDR by modeling p-values as arising from a beta-uniform mixture (BUM) distribution. Unfortunately, the BUM approach is reliable only in settings where the assumed model accurately represents the actual distribution of p-values. METHODS A method called the spacings LOESS histogram (SPLOSH) is proposed for estimating the conditional FDR (cFDR), the expected proportion of false positives conditioned on having k 'significant' findings. SPLOSH is designed to be more stable than the q-value and applicable in a wider variety of settings than BUM. RESULTS In a simulation study and data analysis example, SPLOSH exhibits the desired characteristics relative to the q-value and BUM. AVAILABILITY The Web site www.stjuderesearch. org/statistics/splosh.html has links to freely available S-plus code to implement the proposed procedure.
AG-MIC: Azure-Based Generalized Flow for Medical Image Classification

Medical image-based research requires heavy computational workload associated with image analysis and collaborative device independent platforms to incorporate expert opinions from multiple institutions. Cloud-based resources such as Microsoft Azure Machine Learning Studio (MAMLS) provide such a platform that is conducive to the medical-image-based data analysis. This paper fosters the advantages of the cloud-based computing frameworks (such as MAMLS) and presents a practical work-flow well-suited for the standard machine learning tasks seen in medical image research viz., binary classification, multi-class learning, regression and so on. The proposed automated generalized workflow allows medical researchers/practitioners to focus on data inferencing rather than dealing with the intricate details of predictive modeling, such as feature and model selection. The scalable architecture of the proposed flow utilizes the MAMLS framework to processes data sets that require partial core storage space in the virtual machine to one complete core storage space in a common flow. Also, the proposed flow invokes multiple feature ranking and predictive models in parallel for automated selection and parameterization of the optimal data model. The performance of the proposed flow is bench-marked on 14 public data sets and four local medical image data sets (~0.12 MB-1.22 GB) using a single common flow, while ensuring better (~8% improvement) or atleast similar generalization capability with respect to existing works.
Further refinement of strong multiplicity one for GL(2)

We obtain a sharp refinement of the strong multiplicity one theorem for the case of unitary non-dihedral cuspidal automorphic representations for GL(2). Given two unitary cuspidal automorphic representations for GL(2) that are not twist-equivalent, we also find sharp lower bounds for the number of places where the Hecke eigenvalues are not equal, for both the general and non-dihedral cases. We then construct examples to demonstrate that these results are sharp.
Characterization of barbiturate-stimulated chloride efflux from rat brain synaptoneurosomes

Membrane chloride (Cl-) permeability was studied in a novel subcellular brain preparation, the synaptoneurosome. Using a radioactive tracer exchange technique, Cl- transport was determined by measuring 36Cl- efflux from rat cerebral cortical synaptoneurosomes. Barbiturates increased 36Cl- efflux in a dose-dependent manner with the following relative order of potency: 5-(1,3-dimethylbutyl)-5-ethyl barbituric acid ((-)-DMBB) greater than pentobarbital greater than secobarbital greater than (+)-DMBB greater than hexobarbital greater than amobarbital greater than mephobarbital. Phenobarbital and barbital were virtually inactive. A good correlation was observed between the potencies of these barbiturates in stimulating 36Cl- efflux and their anesthetic potencies in mice (r = 0.90, p less than 0.01) and their abilities to enhance [3H] diazepam binding to brain membranes (r = 0.77, p less than 0.05). The effect of pentobarbital in enhancing 36Cl- efflux was reversed by the gamma-aminobutyric acid (GABA) antagonists picrotoxin and bicuculline. Picrotoxin and bicuculline both decreased 36Cl- efflux in the absence of pentobarbital, suggesting the presence of endogenous GABA. Incubation of synaptoneurosomes with 4,4′-di- isothiocyano- or dinitro-2,2′-disulfonic acid stilbene, inhibitors of anion transport, also decreased both basal and pentobarbital-induced 36Cl- efflux. Pentobarbital (500 microM) was most effective in inducing 36Cl- efflux in the cerebellum, hippocampus, and cortex (23.7, 23.6, and 22.5%, respectively), and was less effective in stimulating 36Cl- efflux in the striatum (15.1%) and pons-medulla (6.2%). The relative efficacy of pentobarbital in enhancing 36Cl- efflux among these various brain regions was highly correlated (r = 0.96, p 0.01) with the relative densities of [35S]-t-butylbicyclophosphorothionate-binding sites, a measure of GABA-gated Cl- channel density. (ABSTRACT TRUNCATED AT 250 WORDS)
Evolutionary multiobjective optimization in dynamic environments: A set of novel benchmark functions

Time varying nature of the constraints, objectives and parameters that characterize several practical optimization problems have led to the field of dynamic optimization with Evolutionary Algorithms. In recent past, very few researchers have concentrated their efforts on the study of Dynamic multi-objective Optimization Problems (DMOPs) where the dynamicity is attributed to multiple objectives of conflicting nature. Considering the lack of a somewhat diverse and challenging set of benchmark functions, in this article, we discuss some ways of designing DMOPs and propose some general techniques for introducing dynamicity in the Pareto Set and in the Pareto Front through shifting, shape variation, slope variation, phase variation, and several other types. We introduce 9 benchmark functions derived from the benchmark suite used for the 2009 IEEE Congress on Evolutionary Computation competition on bound-constrained and static MO optimization algorithms. Additionally a variant of multiobjective EA based on decomposition (MOEA/D) have been put forward and tested along with peer algorithms to evaluate the newly proposed benchmarks.
EFFECT OF EXTRACELLULAR pH ON CONTRACTILE RESPONSES OF THE GUINEA‐PIG VAS DEFERENS

1. Effects of changing the pH of the bathing solution (7.0, 7.4 and 7.8) on the contractile response of the guinea‐pig isolated vas deferens to ATP, noradrenaline (NA) and ATP in the presence of NA or electrical field stimulation (EFS) were investigated.
Celecoxib derivatives induce apoptosis via the disruption of mitochondrial membrane potential and activation of caspase 9

Celecoxib is a potent nonsteroid antiinflammatory drug (NSAID) that has shown great promise in cancer chemoprevention and treatment. The tumor suppression activity of celecoxib and other NSAIDs have been related to the induction of apoptosis in many cancer cell lines and animal models. While celecoxib is a specific inhibitor of cyclooxygenase (COX)‐2, recent data indicate that its apoptotic properties may also be mediated through COX‐independent pathways. In our study, we evaluated second generation celecoxib derivatives, lacking COX‐2 inhibitory activity, in a premalignant and malignant human oral cell culture model to determine their potential anticancer effect and mechanisms responsible for the COX‐independent apoptotic activity. Celecoxib and its derivatives delayed the progression of cells through the G2/M phase and induced apoptosis. The derivatives with apolar substituents at the terminal phenyl moiety of celecoxib greatly enhanced apoptosis and cell cycle delay. Apoptosis and cell cycle arrest appeared to be independent of derivative induced inhibition of PDK1 and phosphorylation of Akt and Erk1/2. Derivatives induced apoptosis was mediated by the cleavage and activation of caspase‐9 and caspase‐3, but not caspase 8, implicating the mitochondrial pathway for apoptosis induction. Inhibitors of caspase‐3 and caspase‐9 and cyclosporin A, a mitochondrial membrane potential stabilizer, attenuated derivative induced apoptosis. Inhibition of caspase‐3 prevented the activation of caspase 8, while the inhibition of caspase‐9 inhibitor blocked activation of both caspase 3 and 8 by the derivatives. Apoptosis was independent of Bcl‐2. These results indicate that the second generation celecoxib derivatives induce apoptosis in human oral cancer lines by the disruption of mitochondrial membrane potential activating caspase 9 and downstream caspase 3 and 8. This suggests that the modification of the celecoxib structure can lead to highly effective COX‐independent growth inhibitory and apoptotic agents in chemoprevention and therapy. © 2004 Wiley‐Liss, Inc.
Acute intermittent porphyria: prevalence of mutations in the porphobilinogen deaminase gene in blood donors in France

Nordmann Y, Puy H, Da Silva V, Simonin S, Robreau AM, Bonaiti C, Phung LN, Deybach JC (Centre Français des Porphyries, Hopital Louis Mourier, Colombes Cedex, France, and the Institut Gustave Roussy, Cedex, France). Acute intermittent porphyria: prevalence of mutations in the porphobilinogen deaminase gene in blood donors in France. J Intern Med 1997; 242: 213–217.
The Mechanisms of Movement Control and Time Estimation in Cervical Dystonia Patients

Traditionally, the pathophysiology of cervical dystonia has been regarded mainly in relation to neurochemical abnormities in the basal ganglia. Recently, however, substantial evidence has emerged for cerebellar involvement. While the absence of neurological “cerebellar signs” in most dystonia patients may be considered at least provoking, there are more subtle indications of cerebellar dysfunction in complex, demanding tasks. Specifically, given the role of the cerebellum in the neural representation of time, in the millisecond range, dysfunction to this structure is considered to be of greater importance than dysfunction of the basal ganglia. In the current study, we investigated the performance of cervical dystonia patients on a computer task known to engage the cerebellum, namely, the interception of a moving target with changing parameters (speed, acceleration, and angle) with a simple response (pushing a button). The cervical dystonia patients achieved significantly worse results than a sample of healthy controls. Our results suggest that the cervical dystonia patients are impaired at integrating incoming visual information with motor responses during the prediction of upcoming actions, an impairment we interpret as evidence of cerebellar dysfunction.
Distinct functions of condensin I and II in mitotic chromosome assembly

Condensin is a protein complex associated with mitotic chromosomes that has been implicated in chromosome condensation. In vertebrates, two types of condensin complexes have recently been identified, called condensin I and II. Here, we show that in mammalian cells condensin II associates with chromatin in prophase, in contrast to condensin I which is cytoplasmic and can thus interact with chromosomes only after nuclear envelope breakdown. RNA interference experiments in conjunction with imaging of live and fixed cells revealed that condensin II is required for chromosome condensation in early prophase, whereas condensin I appears to be dispensable at this stage. By contrast, condensin I is required for the complete dissociation of cohesin from chromosome arms, for chromosome shortening and for normal timing of progression through prometaphase and metaphase, whereas normal condensin II levels are dispensable for these processes. After depletion of both condensin complexes, the onset of chromosome condensation is delayed until the end of prophase, but is then initiated rapidly before nuclear envelope breakdown. These results reveal that condensin II and I associate with chromosomes sequentially and have distinct functions in mitotic chromosome assembly.