Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Examination Is More Predictive of Ambulation Recovery Than CT Lesion Location Following Subcortical Ischemic Stroke

Stroke outcome predictions based on neuroimaging assessments of lesion size, cortical vs. subcortical location, or lobes involved have not been clinically useful. In order to assess the value of an "arterial distribution" outcome schema for subcortical stroke, we reviewed the CT scans of three hundred patients to find fourteen that were obtained two or more days following ischemic stroke which showed lesions restricted to either the lateral lenticulostriate (LLS) or anterior choroidal (AC) arterial distributions. Films were reviewed by two neurologists blinded to the clinical status. Motor paresis and hemisensory deficits were scored at the time of inpatient rehabilitation hospital admission by the staff neurologist having access to the CTS result but unaware of this study. Functional outcome was assessed by Life Table Analysis of the Barthel Index ambulation subscore recorded up to six months post-stroke by rehabilitation team members unaware of CT results. Of the fourteen patients, five had LLS lesions and had a 43 percent probability of becoming independent ambulators. The remaining nine had AC lesions and had a 23 percent probability of becoming independent ambulators (P = N.S., Haenszel-Mantel test). Patients with isolated motor deficits had a 70 percent probability of reaching independent ambulation vs. a 0 percent probability of independent ambulation for those with motor plus hemisensory deficits (P <0.05, Haenszel-Mantel test). These data indicate that ambulation recovery following subcortical stroke is better predicted by clinical evaluation of neurologic impairment than by CT assessment of arterial distribution affected.
Changes in electroencephalographic activity during observation, preparation, and execution of a motor learning task

This study aimed to compare electroencephalographic (EEG) activity between high- and low-motor learning groups (n = 10 each) during observation of, preparation for, and execution of a motor learning task. The subjects performed a ball rotation task in which two balls were rotated clockwise with the right hand. Each trial started with a rest period (5 s), subjects then observed the task action on a computer screen (30 s), this was followed by another rest (5 s), preparation for performing the action (5 s), and finally action execution (30 s); five trials were performed. The number of rotations during execution and EEG activities during observation, preparation, and execution were recorded. The EEG data of the high-motor learning group were compared with those of the low-motor learning group and were analyzed using exact low-resolution electromagnetic tomography (eLORETA). The left sensorimotor and parietal areas of the high-motor learning group showed a greater decrease in the alpha-2 (10.5–12.0 Hz) and beta-2 (18.5–21.0 Hz) rhythms than those of the low-motor learning group during all three phases of the trials. The study results suggest that the decreases in the alpha-2 and beta-2 rhythms in these areas during observation, preparation, and execution are associated with motor skill improvement.
Protein Kinase Cθ Focusing at the cSMAC Is a Consequence rather than Cause of TCR Signaling and Is Dependent on the MEK/ERK Pathway1

Correlation between protein kinase Cθ focusing within the central supramolecular activation cluster (cSMAC) of the immunological synapse and optimal TCR/costimulatory receptor ligation was interpreted to imply that PKCθ focusing is required for productive signaling. However, this notion has been called into question and competing data suggest that the cSMAC contributes to receptor down-modulation. The observation that PKCθ focusing at the cSMAC is promoted by CD28 coligation, and also that it occurs late after proximal tyrosine phosphorylation events have been initiated, has led us to investigate an alternative possibility that PKCθ focusing might be a consequence rather than a cause of productive integrated signaling. Indeed, we found that inhibition of the downstream signaling molecules MEK and PI3K (but not of calcineurin, NF-κB, JNK, or p38 MAPK) significantly prevented the focusing of PKCθ at the cSMAC. It recently has been suggested that the cSMAC may be associated with TCR degradation and signal termination. Using MEK inhibition as a tool, we observed that absence of detectable PKCθ focusing had no significant effect on TCR down-modulation or duration of CD3ζ phosphorylation. Our results suggest that PKCθ focusing at the cSMAC occurs as a consequence of productive integrated downstream signaling at least at the level of MEK. If PKCθ focusing accurately reflects the cSMAC as a whole, then our data also argue against the cSMAC as being required for proximal TCR signal termination.
Predictive value of early serum cytokine changes on long-term interferon beta-1a efficacy in multiple sclerosis

Background: In a previous study, we had evaluated short-term effects of interferon beta-1a (IFNB-1a) 44 μg s.c. three times per week treatment on serum levels of IFN-gamma (IFNG), IL-23, IL-17, IL-10, IL-9, IL-4 and TGF-beta (TGFB) and found a reduction only in IL-17 and IL-23 levels after 2 months of treatment. Methods: Using the same multiple sclerosis (MS) cohort, we assessed the predictive value of early cytokine level changes (difference between 2nd month and baseline levels as measured by ELISA) on the efficacy of long-term IFNB-1a treatment. Results: The alteration in IFNG levels of patients without any relapse was statistically lower than that of patients having one or more relapses (p = 0.019, Student's t-test). When patients with or without expanded disability severity scale (EDSS) progression were compared, none of the cytokine level changes showed a significant difference between groups. IL-17 and IL-23 level changes did not predict relapse and EDSS progression in IFNB-1a-treated MS patients. Conclusion: Our results show that the predictive power of early IFNG measurement on relapse occurrence may potentially extend a time span of several years.
Intra-artery infusion of recombinant human erythropoietin reduces blood–brain barrier disruption in rats following cerebral ischemia and reperfusion

Objectives: Intra-artery infusion of recombinant human erythropoietin (rhEPO) has recently been reported to confer neuroprotection against cerebral ischemia-reperfusion injury in animal models; however, the molecular mechanisms are still under investigation. The present study focused on the specific mechanism involved in blood–brain barrier (BBB) disruption. Methods: Thirty-six male and nine female Sprague Dawley rats were subjected to middle cerebral artery (MCA) occlusion to induce focal cerebral ischemia, and administrated rhEPO at a dose of 800 U/kg through MCA infusion at the beginning of reperfusion. Neurobehavioral deficits, brain edema, and infarct volume were evaluated after 2 h of ischemia and 24 h of reperfusion. BBB permeability was assessed by quantifying the extravasation of Evans blue (EB) dye. The expression of tight junction proteins and matrix metalloproteinases (MMPs) (Claudin-5, Occludin, MMP-2, and MMP-9) in microvessels were detected by immunofluorescence and western blot. The activities of MMPs in the cerebral microvessels were determined by gelatin zymography. Results: Treatment with rhEPO through the MCA strongly alleviated infarct volume, brain edema, and improved neurobehavioral outcomes in male and female rats. In addition, rhEPO remarkably suppressed the EB extravasation induced by brain ischemia. Furthermore, rhEPO prevented degradation of Claudin-5 and Occludin, and reduced the expression and activity of MMP-2 and MMP-9 in isolated brain microvessels. Conclusions: Treatment with rhEPO through MCA infusion prevented brain edema formation and infarction through inhibition of MMP-mediated BBB disruption in acute ischemic stroke.
Calcitriol Suppresses Antiretinal Autoimmunity through Inhibitory Effects on the Th17 Effector Response 1

Experimental autoimmune uveitis (EAU) serves as a model for human autoimmune uveitis and for cell-mediated autoimmunity in general. EAU induced in mice by immunization with the retinal Ag interphotoreceptor retinoid-binding protein in CFA is driven by the Th17 response. Oral calcitriol (1,25-dihydroxyvitamin D3) prevented as well as partly reversed disease and suppressed immunological responses. In vitro, calcitriol directly suppressed IL-17 induction in purified naive CD4+ T cells without inhibiting Th17 lineage commitment, as reflected by unaltered RORγt, STAT3, and FoxP3 expression. In contrast, in vivo treatment with calcitriol of mice challenged for EAU impaired commitment to the Th17 lineage, as judged by reduction of both RORγt and IL-17 in CD4+ T cells. Innate immune response parameters in draining lymph nodes of treated mice were suppressed, as was production of IL-1, IL-6, TNF-α, and IL-12/IL-23p40, but not IL-10, by explanted splenic dendritic cells (DC). Finally, supernatants of calcitriol-conditioned bone marrow-derived DC had reduced ability to support Th17 polarization of naive CD4+ T cells in vitro and in vivo. Thus, calcitriol appears to suppress autoimmunity by inhibiting the Th17 response at several levels, including the ability of DC to support priming of Th17 cells, the ability of CD4+ T cells to commit to the Th17 lineage, and the ability of committed Th17 T cells to produce IL-17.
Association of ALOX5AP rs10507391/SG13S114 A>T polymorphism with cerebral infarction in the Chinese population: a meta-analysis study

Various studies have investigated that the single nucleotide polymorphisms (SNPs) rs10507391/SG13S114 A>T polymorphism could increase the risk of cerebral infarction, however these results still remain controversial. Therefore we conducted a meta-analysis to estimate the association of the 5-lipoxygenase-activating protein gene (ALOX5AP) rs10507391/SG13S114 A > T polymorphism with the incidence of cerebral infarction in the Chinese population. Our researchers searched PubMed, Embase, Web of Science databases, China Biological Medicine Database (CBMD), Wanfang Chinese database, and the Chinese National Knowledge Infrastructure (CNKI) database. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the strength of the association between the ALOX5AP rs10507391/SG13S114 A>T polymorphism and incidence of cerebral infarction. A total of 12 eligible studies including 6,844 cases and 7,850 controls based on the search criteria were involved in this meta-analysis. The distributions of genotypes in the cases and controls were all in agreement with Hardy-Weinberg equilibrium. We observed that the ALOX5AP rs10507391/SG13S114 A>T polymorphism carried with T allele contrast model, the homozygote codominant model, the heterozygote codominant model, the dominant model and the recessive model (all the models p > 0.05) had no risk of cerebral infarction when all studies were pooled into the meta-analysis. The results of the meta-analysis indicate that ALOX5AP rs10507391/SG13S114 A>T polymorphism is not associated with the risk of cerebral infarction in the Chinese population.
Association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke in the Chinese population: a meta-analysis

Purpose: The association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke (IS) has been extensively studied; however, the results from genetic association studies have been inconsistent even in the Chinese population. As far as we know, there was no previous meta-analysis concerning this association in the Chinese population. Therefore, the aim of our meta-analysis was to further evaluate the association in the Chinese population. Methods: We collected all of the relevant studies from Pubmed, OVID, Embase, Chinese Wan Fang database, CNKI, Chongqing VIP database and CBM up to August 2014. The available data was analyzed by Stata (version 12.0). We used odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to present the strength of the association. Heterogeneity was evaluated by the Q-test and I2 statistic. Different genetic models, subgroup analysis, publication bias and sensitivity analysis were used to improve the comprehensive understanding. Results: The results showed a significant association between the MTHFR gene C677T polymorphism and IS in six genetic models (additive model: OR = 1.34, 95%CI: 1.17∼1.54, p < 0.001; dominant model: OR = 1.44, 95% CI:1.26∼1.64, p < 0.001; recessive model: OR = 1.45, 95% CI: 1.15∼1.83, p = 0.001; heterozygote model: OR = 1.35, 95% CI: 1.18∼1.55, p < 0.001; homozygote model: OR = 1.80, 95% CI: 1.34∼2.41, p < 0.001; and allelic model: OR = 1.34, 95% CI: 1.17∼1.53, p < 0.001) based on the overall population, as well as subgroup analysis. In addition, the similar results were obtained in the sensitivity analysis based on studies with the high quality. Conclusions: This meta-analysis presented a significant association between the MTHFR gene C677T polymorphism and IS, the T allele might be a risk factor for IS in the Chinese population.
Availability analysis of repairable redundant system with three types of failures subject to common cause failure

This paper deals with the availability analysis of a redundant system consisting of N-non-identical components and S warm standby components under the care of single repair facility. The system may fail due to three reasons: 1) human error such as wrong adjustments in the design or development phase of the system or system may undergo damage during maintenance; 2) hardware failure; and 3) software failure. The incorporation of common cause failure gives the major impact on the system performance since it may cause dependant failures of some or all components of the system. An irreducible Markov process is used to construct the system of governing differential equations associated with three types of failure subject to common cause failure. The system availability for different configurations under transient condition is examined by using a numerical approach based on Runge-Kutta method of fourth order. Further, the sensitivity analysis is facilitated to demonstrate the validity of analytical results by taking a numerical illustration. The effect of different parameters on system performance indices are demonstrated graphically.
Immunosuppressive Myeloid-Derived Suppressor Cells Can Be Converted into Immunogenic APCs with the Help of Activated NKT Cells: An Alternative Cell-Based Antitumor Vaccine1

Myeloid-derived suppressor cells (MDSCs), which are known to be accumulated in the blood, spleen, and bone marrow of tumor-bearing mice and cancer patients, were tested as APCs for a cellular vaccine because they have phenotypical similarity with inflammatory monocytes and may be differentiated from the same precursors as monocytes. Although MDSCs have immunosuppressive properties, in vivo transferred MDSCs, which present tumor Ag and NKT cell ligand (α-galactosylceramide), significantly prolonged survival time in metastatic tumor-bearing mice in a CD8+ cell-, NK cell-, and NKT cell-dependent manner vs a CD4+ T cell- and host dendritic cell-independent manner. Major concerns about using MDSCs as APCs in a vaccine are their suppression of CTLs and their induction of Foxp3+ regulatory T cells. However, α-galactosylceramide-loaded MDSCs did not suppress CD4+ and CD8+ T cells and allowed for the generation of Ag-specific CTL immunity without increasing the generation of regulatory T cells. Furthermore, stimulation with activated NKT cells induced changes on MDSCs in phenotypical or maturation markers, including CD11b, CD11c, and CD86. Taken together, these findings suggest that NKT cells facilitate the conversion of immunosuppressive MDSCs into immunogenic APCs, eliciting successful antitumor immunity and providing the basis for alternative cell-based vaccines.
MAIL Regulates Human Monocyte IL-6 Production

IL-6 is a pleiotropic cytokine implicated in the pathogenesis of disorders such as sepsis and cancer. We noted that human monocytes are excellent producers of IL-6 as compared with monocyte-derived macrophages. Because macrophages from molecule containing ankyrin repeats induced by LPS (MAIL) knockout animals have suppressed IL-6 production, we hypothesized that regulation of MAIL is key to IL-6 production in humans and may explain the differences between human monocytes and macrophages. To test this hypothesis fresh human monocytes and monocyte-derived macrophages were compared for MAIL expression in response to LPS. LPS-induced monocyte MAIL expression was highly inducible and transient. Importantly for our hypothesis MAIL protein expression was suppressed during differentiation of monocytes to macrophages. Of note, the human MAIL protein detected was the 80 kDa MAIL-L form and human MAIL showed nuclear localization. Human MAIL-L bound to p50 subunit of the NF-κB and increased IL-6 luciferase promoter activity in a cEBPβ, NF-κB, and AP-1-dependent fashion. Like the differences in MAIL induction, monocytes produced 6-fold more IL-6 compared with macrophages (81.7 ± 29.7 vs 12.6 ± 6.8 ng/ml). Furthermore, suppression of MAIL by small interfering RNA decreased the production of IL-6 significantly in both THP-1 cells and in primary monocytes. Costimulation of monocytes with LPS and muramyl dipeptide induced an enhanced IL-6 response that was suppressed by siMAIL. Our data suggests that MAIL is a key regulator of IL-6 production in human monocytes and plays an important role in both TLR and NOD-like receptor ligand induced inflammation.
Transient analysis of a fluid queue driven by a chain sequenced birth and death process with catastrophes

In this paper, we analyse the transient behaviour of a fluid queue modulated by a birth and death processes (BDPs) whose birth and death rates are suggested by a chain sequence and catastrophes. We derive a system of differential equations satisfied by this fluid model. We employ the Laplace transform technique and continued fraction methodology to obtain a simple closed form transient state probability distribution. Also we find the distribution of busy period and analyse the system when there are no catastrophes.
Asthma-Related Environmental Fungus, Alternaria, Activates Dendritic Cells and Produces Potent Th2 Adjuvant Activity1

Asthma is thought to result from dysregulated Th2-like airway inflammatory responses to the environment. Although the etiology of asthma is not fully understood in humans, clinical and epidemiological evidence suggest a potential link between exposure to environmental fungi, such as Alternaria, and development and/or exacerbation of asthma. The goal of this project was to investigate the mechanisms of airway Th2 responses by using Alternaria as a clinically relevant model for environmental exposure. Airway exposure of naive animals to an experimental Ag, OVA, or a common allergen, short ragweed pollen, induced no or minimal immune responses to these Ags. In contrast, mice developed strong Th2-like immune responses when they were exposed to these Ags in the presence of Alternaria extract. Extracts of other fungi, such as Aspergillus and Candida, showed similar Th2 adjuvant effects, albeit not as potently. Alternaria stimulated bone marrow-derived dendritic cells (DCs) to express MHC class II and costimulatory molecules, including OX40 ligand, in vitro. Importantly, Alternaria inhibited IL-12 production by activated DCs, and DCs exposed to Alternaria enhanced Th2 polarization of CD4+ T cells. Furthermore, adoptive airway transfer of DCs, which had been pulsed with OVA in the presence of Alternaria, showed that the recipient mice had enhanced IgE Ab production and Th2-like airway responses to OVA. Thus, the asthma-related environmental fungus Alternaria produces potent Th2-like adjuvant effects in the airways. Such immunogenic properties of certain environmental fungi may explain their strong relationships with human asthma and allergic diseases.
Golden section search over hyper-rectangle: a direct search method

This paper generalises the golden section optimal search method to higher dimensional optimisation problem. The method is applicable to a strict quasi-convex function of N-variables over an N-dimensional hyper rectangle. An algorithm is proposed in N-dimension. The algorithm is illustrated graphically in two dimensions and verified through several test functions in higher dimension using MATLAB.
Association between serum uric acid levels and cerebral white matter lesions in Chinese individuals

Purpose/aim of the study: We aimed to evaluate the association between serum uric acid (SUA) levels and cerebral white matter lesions (WMLs) in Chinese individuals. Material and methods: We prospectively identified patients aged 50 years and older in neurology department from July 2014 to March 2015. Both periventricular WMLs (P-WMLs) and deep WMLs (D-WMLs) were identified on magnetic resonance imanging (MRI) scans and the severity was graded using the Fazekas method. Multivariate logistic regression analyses were performed to examine the association between SUA and WMLs. Results: A total of 480 eligible participants were enrolled in this study. SUA level in severe group was much higher than that in mild group (for P-WMLs: 320.21 ± 79.97 vs. 286.29 ± 70.18, p = 0.000; for D-WMLs: 314.71 ± 74.74 vs. 290.07 ± 74.04, p = 0.031). Subgroup analyses showed that higher SUA level was associated with higher severity of P-WMLs in women, but not in male patients. Multivariate logistic regression analyses showed that SUA was still associated with increased risk of higher severity of P-WMLs (OR = 1.003, 95% = 1.000–1.006), but not D-WMLs. Conclusion: Elevated SUA level was independently associated with greater odds of higher severity of P-WMLs, particularly in women.
Lipídio: fator de risco e prevenção do câncer de mama

The hypothesis that a high fat diet promotes the development of postmenopausal breast cancer is supported by case-controls studies that show a strong correlation between fat intake and breast cancer rates. On the other hand, high fat intake is not correlated with breast cancer in cohort studies. In view of these conflicting findings, it has been difficult to propose nutritional recommendations for the prevention of breast cancer. Animal studies and recent observations in humans have shown that a diet high in polyunsaturated fatty acids stimulates several stages in the development of mammary cancer. Some evidences show that fish oil-derived w-3 fatty acids seem to prevent cancer by influencing the activity of enzymes and proteins related to cell proliferation. Thus, epidemiological studies that integrate the interactions of specific fatty acids with hormone catabolism, protective nutritional factors and risk factors associated with breast cancer are needed. In this article we will discuss protective factors, risk factors and qualitative and quantitative implications of dietary fatty acids in breast cancer.