Miracle-dz/UniFAR-FTUs huggingface dataset:
Bleeding risk and reversal strategies for old and new anticoagulants and antiplatelet agents

Summary. The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. In the case of severe bleeding in a patient who uses anticoagulant agents or when a patient on anticoagulants needs to undergo an urgent invasive procedure, it may be useful to reverse anticoagulant treatment. Conventional anticoagulants such as vitamin K antagonists may be neutralized by administration of vitamin K or prothrombin complex concentrates, whereas heparin and heparin derivatives can be counteracted by protamine sulphate. The anti‐hemostatic effect of aspirin and other antiplatelet strategies can be corrected by the administration of platelet concentrate and/or desmopressin, if needed. Recently, a new generation of anticoagulants with a greater specificity towards activated coagulation factors as well as new antiplatelet agents have been introduced and these drugs show promising results in clinical studies. A limitation of these new agents may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs, although experimental studies show hopeful results for some of these agents.
Anti-inflammatory and anticancer effects of flavonol glycosides from Diplotaxis harra through GSK3β regulation in intestinal cells

Abstract Context and objective: Diplotaxis harra (Forssk.) Boiss. (Brassicaceae) is traditionally used as an antidiabetic, anti-inflammatory or anticancer agent. In these pathologies, the glycogen synthase kinase 3 β (GSK3β) is overactivated and represents an interesting therapeutic target. Several flavonoids can inhibit GSK3β and the purpose of this study was to search for the compounds in Diplotaxis harra which are able to modulate GSK3β. Materials and methods: Methanol extracts from D. harra flowers were prepared and the bio-guided fractionation of their active compounds was performed using inflammatory [protease-activated receptor 2 (PAR2)-stimulated IEC6 cells] and cancer (human Caco-2 cell line) intestinal cells. 50–100 μg/mL of fractions or compounds purified by HPLC were incubated with cells whose inhibited form of GSK3β (Pser9 GSK3β) and survival were analyzed by Western blot at 1 h and colorimetric assay at 24 h, respectively. LC-UV-MS profiles and MS-MS spectra were used for the characterization of extracts and flavonoids-enriched fractions, and the identification of pure flavonoids was achieved by MS and NMR analysis. Results: The methanol extract from D. harra flowers and its flavonoid-enriched fraction inhibit GSK3β in PAR2-stimulated IEC6 cells. GSK3β inhibition by the flavonoid-enriched D. harra fraction was dependent on PKC activation. The flavonoid-enriched D. harra fraction and its purified compound isorhamnetin-3,7-di-O-glucoside induced a 20% decrease of PAR2-stimulated IEC6 and Caco-2 cell survival. Importantly, normal cells (non-stimulated IEC6 cells) were spared by these treatments. Conclusion: This work indicates that flavonoids from D. harra display cytotoxic activity against inflammatory and cancer intestinal cells which could depend on GSK3β inhibition.
Monocytes differentiated with GM‐CSF and IL‐15 initiate Th17 and Th1 responses that are contact‐dependent and mediated by IL‐15

Distinct types of DCs are generated from monocytes using GM‐CSF with IL‐4 (IL4‐DC) or IL‐15 (IL15‐DC). IL15‐DCs are potent inducers of antigen‐specific CD8+ T cells, display a phenotype similar to CD14+ cells commonly described in chronically inflamed tissues, and produce high levels of IL‐1β and IL‐15 in response to TLR4 stimulation. As these cytokines promote Th17 responses, which are also associated with inflammatory diseases, I hypothesized that TLR‐primed IL15‐DCs favor Th17 activation over IL4‐DCs. Compared with IL4‐DCs, IL15‐DCs stimulated with TLR agonists secreted significantly higher concentrations of the Th17‐promoting factors, IL‐1β, IL‐6, IL‐23, and CCL20, and lower levels of the Th1 cytokine, IL‐12. In addition, IL15‐DCs and not IL4‐DCs up‐regulated IL‐15 on the cell surface in response to TLR agonists. IL15‐DCs primed with TLR3 or TLR4 agonists triggered Th17 (IL‐17, IL‐22, and/or IFN‐γ) and Th1 (IFN‐γ) responses, whereas IL4‐DCs primed with the same TLR agonists activated Th1 (IFN‐γ) responses. Secretion of IL‐17 and IFN‐γ required contact with TLR‐primed IL15‐DC, and IFN‐γ production was mediated by membrane‐bound IL‐15. These findings identify key differences in monocyte‐derived DCs, which impact adaptive immunity, and provide primary evidence that IL‐15 promotes Th17 and Th1 responses by skewing monocytes into IL15‐DC.
[A clinical study of femoral head osteonecrosis in patients with systemic lupus erythematosus.].

OBJECTIVE To investigate the clinical features of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE). METHODS The consecutive 461 SLE patients who underwent inpatient care in China-Japan Friendship Hospital were reviewed, the clinical data of 32 cases complicated with ONFH and 64 without ONFH as control was studied. RESULTS The incidence of ONFH in 461 SLE patients was 6.94%. 65.63% of the ONFH was diagnosed within the first 3 years of SLE. It was found that the incidence of vasculitis, osteoporosis, high level of blood platelet, serum low density lipoprotein cholesterol (LDL-C) and fibrinogen was higher in SLE patients with ONFH than that in SLE patients without ONFH (P < 0.05). When compared with controls, the ONFH initial glucocorticoid dosage and accumulative dosage of glucocorticoid within the first month or six months were significantly higher in SLE patients with ONFH (P < 0.05). There was no significant difference between two groups in sex, age, duration of SLE, dental ulcer, Raynaud's phenomenon, hypocalcemia, renal diseases, hypertension, anemia, positive anticardiolipin antibodies and immunosuppresive treatment (P > 0.05). CONCLUSION The incidence of ONFH in patients with SLE is relatively high within the first 3 years of SLE. The SLE patients with ONFH are more likely to have such clinical features as vasculitis, osteoporosis, high level of blood platelet, serum LDL-C and fibrinogen and exposed to high-dose glucocorticoid therapy.
Mobility and bioavailability of trace metals in sulfidic coastal sediments

High concentrations of Hg, Cd, Pb, Cu, and Zn were found in the euxinic sediment of the inner archipelago of Stockholm. In the sulfide‐rich sediment, they are precipitated as metal sulfides with low dissolving capacity and bioavailability. In two experiments, the significance of acid‐volatile sulfide (AVS) and dissolved sulfides for mobility, bioavailability, and toxicity of metals were studied by oxygenation of intact sediment cores. Influence of bioturbating deposit‐feeding amphipods, that is, Monoporeia affinis, was examined on studied sediment processes. Results showed a low mobility of most metals except Cd and Zn. Bioturbation did not enhance mobility. Cd and Zn, released from the sediment, were not bioaccumulated in amphipods. In contrast, the less mobile metals Hg and Pb were bioaccumulated. A low toxicity of contaminated sediments, in terms of mortality and embryonic malformations of amphipods, was recorded. Results indicate that Cd, Zn, and Cu are comparatively unavailable after oxygenation of the metal sulfides. Similar results were recorded in contaminated sediments differing in redox potential, AVS, dissolved sulfides, and organic contents, suggesting that other metal ligands, in addition to AVS, are important for metal bioavailability and toxicity in anoxic and suboxic environments.
The effects of high physical activity on pharmacokinetic drug interactions

Introduction: With the development of new drugs, it is common practice for drug manufacturers to measure their pharmacokinetic parameters. This testing involves the discovery of the absorption, distribution, metabolic, excretory and toxicological properties of drugs. The testing is usually done in non-stressful conditions at rest, however, this does not necessarily tell the entire picture as there is increasing knowledge about the effects that high levels of physical activity can have on the pharmacokinetics of some medications. Areas covered: This review discusses the alterations that physical activity can have on the absorption, distribution, metabolism and elimination parameters of commonly used medications, and clinical outcomes data are reported when known, demonstrating that an interaction exists between exercise and certain medications. This drug–exercise pharmacokinetic interaction alters the performance of medications especially under conditions where exercise is performed for a long period of time. Particular medications that may be affected are those with a narrow therapeutic dosing range, such as digoxin, theophylline and warfarin. Other important medications include insulin and those administered via a transdermal patch drug delivery system. For this review, a literature search was performed between 1966 and 2010. Expert opinion: Patients and healthcare providers should be aware that exercise can adversely affect the way some medications are intended to work. Patients taking certain medications should be closely monitored when performing high amounts of physical activity.
[Clinical diagnosis and treatment of male Kallmann syndrome].

OBJECTIVE To investigate the diagnosis and treatment of male Kallmann syndrome. METHODS We retrospectively analyzed the clinical data of 12 cases of male Kallmann syndrome, 3 treated for male sterility and the other 9 for secondary sex characteristics dysplasia and external genitalia developmental anomalies, all by combined replacement therapy with human chorionic gonadotropin (hCG), human menopause gonadotropin (hMG) and testosterone undecanoate for 6 months to 3 years. We compared the secondary sexual development and serum sex hormone levels of the patients before and after treatment. RESULTS After 9 months of treatment, all the 12 patients showed significant improvement in the penile length, testicular volume and sex hormone levels (P < 0.01), with different degrees of promotion of the secondary sexual development. Three married cases could have normal sexual intercourse, and one of them achieved normal pregnancy. CONCLUSION The clinical characteristics of Kallmann syndrome include lack of gonadotropins, lower gonad function and loss or reduction of olfactory sensation. Replacement therapy with hCG, hMG and androgens is an effective treatment method. However, no effective therapy is now available for olfactory dysfunction. Early diagnosis and hormone replacement therapy can best alleviate its clinical symptoms and eventually achieve fertility.
[Mechanism of Apoptosis for Resveratrol-mediated Reversing the Drug-resistance of AML HL-60/ADR cells].

OBJECTIVE To explore the mechanism of apoptosis for resvertrol-mediated reversing the drug-resistance of AML HL-60/ADR cells. METHODS The HL-60/ADR cells were divided into 4 groups: control group, adriamycin (ADR)-treated group, resveratrol(Res)-treated group and ADR+Res-treated group. The inhibitory rate of cell proliferation was analyzed by CCK-8 method. The auto-fluorescence intensity of intracellular ADR and the apoptotic rate of HL-60/ADR cells were detected by flow cytometry. The mRNA expression levels of multidrug-resistance associated protein-1(MRP1), anti-apoptotic gene BCL-2 and pro-apoptotic gene BAX were analyzed by real-time fluorescence quantitative RT-PCR. The protein expression levels of MRP1, BCL-2 and BAX were detected by Western blot. RESULTS The maximal inhibition rates of cell proliferation were 44%, 61%, 76% and 81%, respectively in different concentration of Res (25, 50, 100, 200 µmol/L) and with concentration-dependent manner(r=0.876, P<0.05). Compared with ADR group (IC50: 8.534±1.111 µmol/L), the half inhibitory concentration (IC50) of HL-60/ADR cells [(1.591±0.373) µmol/L] decreased significantly in ADR+Res group(P<0.05). The auto-fluorescence intensity of ADR in HL-60/ADR cells of ADR+Res group increased significantly (P<0.05). The apoptotic rate of HL-60/ADR cells in Res or ADR+Res group increased significantly (P<0.05). The mRNA expression levels of MRP1 and Bcl-2 in Res or ADR+Res groups decreased and BAX increased significantly (P<0.05). The protein expression levels of MRP1 and BCL-2 were decreased, BAX increased significantly in Res or ADR+Res group (P<0.05). CONCLUSION Resveratrol shows the effect of reversing the drug resisitance of HL-60/ADR cells in acute myeloid leukemia, possibly via promoting the apoptosis of HL-60/ADR cells and inhibiting the expression of MRP1, which may be related with the inhibition of BCL-2 expression and the promotion of BAX expression.
Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure.

In cardiac and skeletal muscle, the sarcoplasmic reticulum (SR) plays a central role in the contraction relaxation cycle of the muscle by virtue of its ability to regulate the intracellular free Ca'+ concentration [Ca'+],. Ca'+ release from the SR increases [Ca'+] (10`mol/L), thus inducing contraction, whereas Ca2` uptake by the SR reduces [Ca'+] (=10-7 mol/L), producing muscle relaxation. In cardiac muscle, the beatto-beat rhythm (contraction-relaxation cycle) is tightly controlled by the regulated release and removal of Ca'+ by the SR. In view of this key role in excitationcontraction coupling, alterations in the SR function are expected to significantly affect cardiac performance. Over the past three decades, varying degrees of defects in the SR Ca'+ uptake function have been identified in different experimental models of heart disease, and the literature has been reviewed extensively.1 ~5More recent analyses using animal models and human failing heart samples suggest that alterations in SR function may be primarily due to alterations in the expression level of mRNAs encoding key SR Ca2' transport proteins. The purpose of this review is to highlight recent advances concerning the regulation of SR gene expression during cardiac hypertrophy and heart failure.
Effects of Antemortem and Postmortem Variables on Human Brain mRNA Quality: A BrainNet Europe Study

Well-characterized and preserved human brain tissue that is prepared and stored in brain banks is an essential resource for research in neurological diseases. This study examined the quality of human brain postmortem tissue from multiple laboratories within the BrainNet Europe brain bank network to identify all possible confounding variables and determine how they may affect RNA quality. Antemortem and postmortem information was retrospectively collected for a large cohort of samples. Total RNA was isolated from anatomically defined brain regions using a standardized procedure; RNA quality was assessed using an Agilent 2100 Bioanalyzer. No significant difference in RNA quality was observed in 6 different brain regions. RNA quality deteriorated with increasing numbers of antemortem events such as hospitalization, coma, respiratory illness, and the use of artificial ventilation; accumulation of such events was associated with elevated hypoxia-inducible factor 1&agr; mRNA expression. Brain pH was found to be a good indicator of RNA quality. There was no correlation of postmortem delay with cerebrospinal fluid pH or RNA quality overall, but some individual RNAs decreased in quality with antemortem events and with postmortem delay. RNA quality did not affect total RNA yield. Determining the factors that are best predictors of RNA quality can help brain banks with selection criteria for storing high-quality brain tissue for research.
NGF Deprivation of Adult Rat Brain Results in Cholinergic Hypofunction and Selective Impairments in Spatial Learning

Cholinergic hypofunction has often been correlated with a variety of behavioural impairments. In the present study, adult Wistar rats were intraventricularly infused with antibodies to nerve growth factor (anti‐NGF) to examine the effects on cholinergic neurons of the basal forebrain, and on behavioural performance. Immunocytochemical techniques indicated that chronically infused anti‐NGF penetrates into the basal forebrain, cortex, striatum, corpus callosum and hippocampus, confirming previous findings after a single injection. Treatment with anti‐NGF for 1 or 2 weeks resulted in a significant decrease of 27‐33% in density of choline acetyltransferase immunostaining of the cholinergic cell bodies in the medial septum and vertical diagonal band, and a 26% reduction in choline acetyltransferase enzyme activity in the septal area. An array of spatial learning Morris water maze tasks was used to distinguish between acquisition skills and the flexible use of learned information in novel tests. Rats subjected to the spatial learning paradigm received anti‐NGF infusion for 2 weeks prior to and for another 2 weeks during the behavioural testing. The anti‐NGF‐treated animals were found to be no different from those receiving control serum in the Morris water maze acquisition task, either in the latency to find the platform or in the time spent searching in the training quadrant when the platform was removed. However, in consecutive extinction trials, anti‐NGF rats continued to search in the empty training quadrant, suggesting the occurrence of perseveration; control rats expanded their search over other areas of the pool. This inflexibility of the anti‐NGF rats was also evident from their difficulty in learning to find a relocated platform in the reversal task. Finally, the anti‐NGF‐treated animals demonstrated hyperactivity in the open field, resembling in this respect the behaviour of animals after septal and fimbria fornix lesions, and during pharmacological cholinergic blockade. While these data support a role for NGF in cholinergic function and spatial learning behaviour, they indicate that deficits in the latter, e.g. those demonstrated in impaired aged rats, may not be attributable selectively to deficits in the function of NGF‐sensitive cholinergic neurons of the basal forebrain.
Natural transfer of conjugative transposon Tn916 between gram-positive and gram-negative bacteria

The conjugative streptococcal transposon Tn916 was found to transfer naturally between a variety of gram-positive and gram-negative eubacteria. Enterococcus faecalis hosting the transposon could serve as a donor for Alcaligenes eutrophus, Citrobacter freundii, and Escherichia coli at frequencies of 10(-6) to 10(-8). No transfer was observed with several phototrophic species. Mating of an E. coli strain carrying Tn916 yielded transconjugants with Bacillus subtilis, Clostridium acetobutylicum, Enterococcus faecalis, and Streptococcus lactis subsp. diacetylactis at frequencies of 10(-4) to 10(-6). Acetobacterium woodii was the only gram-positive organism tested that did not accept the transposon from a gram-negative donor. The results prove the ability of conjugative transposable elements such as Tn916 for natural cross-species gene transfer, thus potentially contributing to bacterial evolution.
Video retrieval using speech and text in video

This paper presents an analysis process of lecture video retrieval with automated video indexing and video search for lecture video databases. The video retrieval extracts the relevant metadata from the two main parts of lecture videos, namely the visual screen and audio tracks. From the visual screen, we firstly detect the slide transition and extract each unique slide frame with its temporal transition considered as the video segment. The textual metadata from slide frames is extracted and then recognized using video OCR technique. Based on OCR results, the corresponding text in video information is saved. Secondly, the speech-to-text analysis is carried out from the audio signal. Sphinx speech recognition models are used for recognition of speech-to-text conversion process. In the proposed work, the combined text information from the visual slide frame and audio signal were used to retrieve the video from the lecture video database. The performance of this combined video retrieval system shows a significant improvement in performance when compared with an individual system built using audio and text in video systems respectively.
Activity, inactivity and quality of life among Lebanese adolescents

Background: The aim of the present study was to investigate recent overweight and obesity prevalence rates for Lebanese adolescents, and to examine differences in physical activity, screen time (sum of time spent in front of TV, computer, and videogames), and health‐related quality of life (HRQOL) for the first time among normal, overweight, and obese adolescents.
Case Report

Autism spectrum disorders are neurodevelopmental disorders that are thought to be caused by a gene-by-environment interaction and in which various immune alterations are reported. We investigate CD4+ T-cell cytokine profiles and subpopulations in 19-year-old monozygotic twins with autism and different comorbidities. CD4+ T cells from the twin with epilepsy produce more interferon-gamma, less interleukin-17, and have an increased interferon-γ/interleukin-4 ratio. CD4+ T cells from the twin with multiple sclerosis exhibit a cytokine profile similar to an age and gender-matched control and a higher percentage of T regulatory (Treg) cells. The twins’ mother’s T cells produce very high levels of both interleukin-17 and interferon-γ. Cytokine and CD4+ T-cell abnormalities in the twins could contribute to or be a result of the manifestation of their divergent comorbidities. A proinflammatory, autoimmune-polarized cytokine profile is observed in this unique family with autism.
Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck

Both p53 tumor suppressor and murine double minute 2 (MDM2) oncoprotein are crucial in carcinogenesis. We hypothesized that MDM2 promoter single nucleotide polymorphisms (SNPs) SNP309 T > G, A2164G, and p53 codon 72 are associated with risk and age at onset of squamous cell carcinoma of head and neck (SCCHN). We genotyped these SNPs in a study of 1,083 Caucasian SCCHN cases and 1,090 cancer‐free controls. Although none of these SNPs individually had a significant effect on risk of SCCHN, nor did their combined putative risk genotypes (i.e., MDM2 SNP309 GT + GG, 2164 AA, and p53 codon 72 CC), we found that individuals with two to three risk genotypes had significantly increased risk of non‐oropharyngeal cancer (OR = 1.42; 95% CI = 1.07–1.88). This increased risk was more pronounced among young subjects, men, smokers, and drinkers. In addition, female patients carrying the MDM2 SNP309 GT and GG genotypes showed a 3‐yr (56.7 yr) and 9‐yr (51.2 yr) earlier age at onset of non‐oropharyngeal cancer (Ptrend = 0.007), respectively, compared with those carrying the TT genotype (60.1 yr). The youngest age (42.5 yr) at onset of non‐oropharyngeal cancer was observed in female patients with the combined MDM2 SNP309 GG and p53 codon 72 CC genotypes. The findings suggest that MDM2 SNP309, A2164G, and p53 codon 72 SNPs may collectively contribute to non‐oropharyngeal cancer risk and that MDM2 SNP309 individually or in combination with p53 codon 72 may accelerate the development of non‐oropharyngeal cancer in women. Further studies with large sample sizes are warranted to validate these results. © 2011 Wiley‐Liss, Inc.