Miracle-dz/UniFAR-FTUs huggingface dataset:
Physical fitness and prior physical activity are both associated with less cortisol secretion during psychosocial stress

ABSTRACT Background: Evidence linking fitness and decreased psychosocial stress comes from studies of athletes and typically relies upon self-report measures. Furthermore, there is little evidence regarding the impact of physical activity (PA) prior to a stressor. The aims of this study were to determine whether fitness and prior PA influence cortisol concentrations during psychosocial stress. Methods: Seventy-five non-athletic participants took part in a submaximal walk prior to the Trier Social Stress Test for Groups (TSST-G). During the walk, fitness was assessed using heart rate (HR). A further 89 participants took part in the TSST-G without the walk. Stress responsiveness was assessed using salivary cortisol collected at 10-min intervals on seven occasions. Results: Hierarchical multiple regression revealed that average walking HR accounted for 9% of the variance in cortisol secretion (P = .016), where a higher HR was associated with higher cortisol secretion. Between-subjects ANCOVA revealed that the walking group had a significantly lower cortisol secretion than the non-walking group (P = .009). Conclusions: These findings indicate that fitter individuals have reduced cortisol secretion during psychosocial stress. They also indicate that prior PA can reduce cortisol concentrations during psychosocial stress and are suggestive of a role of PA in reducing the impact of stress on health.
Some hemostasis variables at the end of the population distributions are risk factors for severe postpartum hemorrhages

Summary. Background: Severe postpartum hemorrhages (PPH) represent a significant cause of maternal morbidity/mortality, but little is known about its hemostasis‐related risk factors. Among the 32 463 women enrolled in the NOHA First cohort, 317 developed severe PPH (S‐PPH group), 1269 non‐severe PPH (NS‐PPH group) and the remaining individuals were considered as control women (C group). Methods: We performed a case–control study, including 317 triplets of women allocated from the three groups that shared the same clinical characteristics as the S‐PPH group. Results: From values obtained 6–9 months after delivery, low (but not‐deficient) levels of fibrinogen, von Willebrand factor (VWF) antigen, factor (F) XI, platelet CD42b, TRAP‐induced increase of platelet CD41a and high values of serum residual prothrombin activity or closure aperture times using the collagen‐ADP cartridge on the PFA‐100® system, and blood group O, were independently associated with a significant risk of severe PPH. Being positive for at least two of these eight variables was found in 1.6%, 3.5% and 20.8% of the women from the C, the NS‐PPH and the S‐PPH groups, respectively, the odds ratio for S‐PPH in such a case being 16.4, 95%CI (6.5–41), P < 0.0001. Conclusions: Women with some hemostasis‐related variables at the low or high end of the population distributions are prone to the severe forms of PPH. Clinical trials will allow us to know if acting on these risk factors can lower the clinical severity of PPH.
Structure-related clustering of gene expression fingerprints of thp-1 cells exposed to smaller polycyclic aromatic hydrocarbons

This study was undertaken to test the hypothesis that structurally similar PAHs induce similar gene expression profiles. THP-1 cells were exposed to a series of 12 selected PAHs at 50 µM for 24 hours and gene expressions profiles were analyzed using both unsupervised and supervised methods. Clustering analysis of gene expression profiles revealed that the 12 tested chemicals were grouped into five clusters. Within each cluster, the gene expression profiles are more similar to each other than to the ones outside the cluster. One-methylanthracene and 1-methylfluorene were found to have the most similar profiles; dibenzothiophene and dibenzofuran were found to share common profiles with fluorine. As expression pattern comparisons were expanded, similarity in genomic fingerprint dropped off dramatically. Prediction analysis of microarrays (PAM) based on the clustering pattern generated 49 predictor genes that can be used for sample discrimination. Moreover, a significant analysis of Microarrays (SAM) identified 598 genes being modulated by tested chemicals with a variety of biological processes, such as cell cycle, metabolism, and protein binding and KEGG pathways being significantly (p < 0.05) affected. It is feasible to distinguish structurally different PAHs based on their genomic fingerprints, which are mechanism based.
Pattern and outcome of medical admissions in a Nigerian rural teaching hospital (2009-2012)

Background: Medical diseases vary depending on the locality and it reflects the pattern of medical admissions into a medical centre. We set out to collect, analyse, present the report of results from Igbinedion University Teaching Hospital to the wider scientific community on pattern and outcome of patients in medical wards in the hospital between January 2009 to December 2012. This we believe would reflect the relative pattern, trend of diseases burden and relative importance of diseases in the hospital locality. Methods: The study was a retrospective descriptive study where data of admission cases in both male and female medical wards were collected (from the admission register with occasional reference to some patients' case notes) and analysed. Results: A total of 1066 patients were admitted during the study period, Male patients constituted 52.5% while female were 47.5% (Male: Female ratio 1.11:1 , age range 14-99 years) while under 20 years, Under 30 years and Elderly constituted 30.1%, 59.3% and 12.5% respectively. Malaria, hypertension, Vaso-occlussive Crisis in Sickle Cell Diseases, Peptic Ulcer Disease, Gastroenteritis and Enteric Fever were the most common diseases admitted during the study period. Infectious and parasitic diseases was found to constitute the majority of diseases admitted. 81.2%, 4.6% and 1.6% of admitted patients were discharged, referred and died respectively. Discussions and Conclusion: The large proportion of patients in younger age groups was likely due to the university community that is located in the same town with the teaching hospital. Elderly patients accounted for 11.1% of total hospitalization similar to value gotten in another Teaching Hospital. The study showed essentially that Infectious diseases constituted the bulk of admission with malaria being the largest single disease. Non-Communicable Diseases (NCDs) were also prominent. Majority of the patients were discharged home with lesser outcome of referral, death and transfer etc.
AVE5026, a new hemisynthetic ultra‐low‐molecular‐weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery – TREK: a dose‐ranging study

Summary. Background: AVE5026 is a new hemisynthetic ultra‐low‐molecular‐weight heparin, with a novel anti‐thrombotic profile resulting from high anti‐factor (F)Xa activity and residual anti‐FIIa activity. AVE5026 is in clinical development for venous thromboembolism (VTE) prevention, a frequent complication after total knee replacement (TKR) surgery. Objectives: This study evaluated the dose‐response of AVE5026 for the prevention of VTE in patients undergoing TKR surgery. Patients/methods: In this parallel‐group, double‐blind, double‐dummy study, 690 patients were randomized, and 678 treated with once‐daily doses of AVE5026 (5, 10, 20, 40, or 60 mg) or enoxaparin 40 mg in the calibrator arm. The primary efficacy end point was VTE until post‐operative day 11, defined as deep vein thrombosis (DVT) detected by bilateral venography, symptomatic DVT, non‐fatal pulmonary embolism (PE) and VTE‐related death. The primary safety outcome was the incidence of major bleeding. Results: The primary efficacy outcome was assessed in 464 patients. There was a significant dose‐response across the five AVE5026 groups for VTE prevention (P < 0.0001), with the incidence of VTE ranging from 5.3% to 44.1% compared with 35.8% in the enoxaparin group and for proximal DVT (P = 0.0002). Also, a significant dose‐response for AVE5026 was seen for major bleeding (P = 0.0231) and any bleeding (P = 0.0003). Six patients in the AVE5026 groups, four in the 60 mg group, experienced major bleeding; none did in the enoxaparin group. Conclusions: The safety and efficacy results of this study suggest that a AVE5026 dose of between 20 and 40 mg presents an adequate benefit‐to‐risk ratio.
Using support vector regression coupled with the genetic algorithm for predicting acute toxicity to the fathead minnow

The potential toxicity of chemicals may present adverse effects to the environment and human health. The quantitative structure–activity relationship (QSAR) provides a useful method for hazard assessment. In this study, we constructed a QSAR model based on a highly heterogeneous data set of 571 compounds from the US Environmental Protection Agency, for predicting acute toxicity to the fathead minnow (Pimephales promelas). An approach coupling support vector regression (SVR) with the genetic algorithm (GA) was developed to build the model. The generated QSAR model showed excellent data fitting and prediction abilities: the squared correlation coefficients (r 2) for the training set and the test set were 0.826 and 0.802, respectively. Only eight critical descriptors, most of which are closely related to the toxicity mechanism, were chosen by GA-SVR, making the derived model readily interpretable. In summary, the successful case reported here highlights that our GA-SVR approach can be used as a general machine learning method for toxicity prediction.
Energy‐efficient single‐clock‐cycle binary comparator

A new fast low‐power single‐clock‐cycle binary comparator is presented. High speed is assured by using parallel‐prefix architecture, whereas low power is guaranteed by reducing the switching activities of the internal nodes. When implemented with the ST 90 nm 1 V CMOS technology, the proposed circuit exhibits a 4.5 GHz maximum running frequency and 0. 77µW/ MHz energy dissipation. Copyright © 2010 John Wiley & Sons, Ltd.
For-Profit Enterprise in Health Care

No issue in health care is more controversial than the role of profit-making enterprise. It is a widely held perception that growth of investor-owned business ventures will fundamentally change the way health care is provided and financed in the United States in coming years. Some argue that an increased business presence will bring needed discipline to health care markets long characterized by excessive costs and inattention to consumer wants. Others fear the loss of traditional community-oriented providers and possible deleterious effects on access and quality of care. There is no shortage of rhetoric on either side but surprisingly little in the way of supporting empirical evidence. This book is the second Institute of Medicine (IOM) study of the for-profit phenomenon. ( The New Health Care for Profit: Doctors and Hospitals in a Competitive Environment , published in 1983, was the first.) And it specifically addresses the question of what is known empirically
Quantitative neurite outgrowth measurement based on image segmentation with topological dependence

The study of neuronal morphology and neurite outgrowth has been enhanced by the combination of imaging informatics and high content screening, in which thousands of images are acquired using robotic fluorescent microscopy. To understand the process of neurite outgrowth in the context of neuroregeneration, we used mouse neuroblastoma N1E115 as our model neuronal cell. Six‐thousand cellular images of four different culture conditions were acquired with two‐channel widefield fluorescent microscopy. We developed a software package called NeuronCyto. It is a fully automatic solution for neurite length measurement and complexity analysis. A novel approach based on topological analysis is presented to segment cells. The detected nuclei were used as references to initialize the level set function. Merging and splitting of cells segments were prevented using dynamic watershed lines based on the constraint of topological dependence. A tracing algorithm was developed to automatically trace neurites and measure their lengths quantitatively on a cell‐by‐cell basis. NeuronCyto analyzes three important biologically relevant features, which are the length, branching complexity, and number of neurites. The application of NeuronCyto on the experiments of Toca‐1 and serum starvation show that the transfection of Toca‐1 cDNA induces longer neurites with more complexities than serum starvation. © 2008 International Society for Advancement of Cytometry
Topological structural alerts modulations of mammalian cell mutagenicity for halogenated derivatives

Genotoxicity is a key toxicity endpoint for current regulatory requirements regarding new and existing chemicals. However, genotoxicity testing is time-consuming and costly, and involves the use of laboratory animals. This has motivated the development of computational approaches, designed to predict genotoxicity without the need to conduct laboratory tests. Currently, many existing computational methods, like quantitative structure–activity relationship (QSAR) models, provide limited information about the possible mechanisms involved in mutagenicity or predictions based on structural alerts (SAs) do not take statistical models into account. This paper describes an attempt to address this problem by using the TOPological Substructural MOlecular Design (TOPS-MODE) approach to develop and validate improved QSAR models for predicting the mutagenicity of a range of halogenated derivatives. Our most predictive model has an accuracy of 94.12%, exhibits excellent cross-validation and external set statistics. A reasonable interpretation of the model in term of SAs was achieved by means of bond contributions to activity. The results obtained led to the following conclusions: primary halogenated derivatives are more mutagenic than secondary ones; and substitution of chlorine by bromine increases mutagenicity while polyhalogenation decreases activity. The paper demonstrates the potential of the TOPS-MODE approach in developing QSAR models for identifying structural alerts for mutagenicity, combining high predictivity with relevant mechanistic interpretation.
Detection of intracellular ADAMTS13, a secreted zinc‐metalloprotease, via flow cytometry

ADAMTS13 is a secreted metalloprotease that cleaves von Willebrand Factor multimers in order to maintain proper homeostasis. A severe deficiency in ADAMTS13 triggers a disorder known as thrombotic thrombocytopenic purpura. At present, ADAMTS13 expression levels are determined by immunoblotting. We established a flow cytometry methodology to detect intracellular ADAMTS13 in liver and kidney cells using a polyclonal antibody, BL154G, and several monoclonal antibodies previously used to detect ADAMTS13 by immunoblotting. The results were validated using confocal microscopy, immunoblotting, and an activity assay (FRETS‐VWF73). We show that labeling ADAMTS13 with specific antibodies and detection by flow cytometry yields results that are comparable with previously established methods for ADAMTS13 detection. Specifically, we compared the endogenous expression levels of ADAMTS13 in various liver cell lines using flow cytometry and obtained results that parallel immunoblot analysis. Knockdown of ADAMTS13 expression via targeted siRNA resulted in significantly reduced median signal, displaying the sensitivity of this detection method. A further analysis of reliability and specificity was achieved through plasmid DNA and transfection reagent dose response studies. The flow cytometry method described here is useful in determining the expression of both endogenous and recombinant forms of intracellular ADAMTS13. Flow cytometry is a convenient, efficient, and cost‐effective way to measure the expression levels of ADAMTS13. Published 2009 Wiley‐Liss, Inc.
Simultaneous flow cytometric quantification of plant nuclear DNA contents over the full range of described angiosperm 2C values

Flow cytometry provides a rapid, accurate, and simple means to determine nuclear DNA contents (C‐value) within plant homogenates. This parameter is extremely useful in a number of applications in basic and applied plant biology; for example, it provides an important starting point for projects involving whole genome sequencing, it facilitates characterization of plant species within natural and agricultural settings, it allows facile identification of engineered plants that are euploid or that represent desired ploidy classes, it points toward studies concerning the role of C‐value in plant growth and development and in response to the environment and in terms of evolutionary fitness, and, in uncovering new and unexpected phenomena (for example endoreduplication), it uncovers new avenues of scientific enquiry. Despite the ease of the method, C‐values have been determined for only around 2% of the described angiosperm (flowering plant) species. Within this small subset, one of the most remarkable observations is the range of 2C values, which spans at least two orders of magnitude. In determining C‐values for new species, technical issues are encountered which relate both to requirement for a method that can provide accurate measurements across this extended dynamic range, and that can accommodate the large amounts of debris which accompanies flow measurements of plant homogenates. In this study, the use of the Accuri C6 flow cytometer for the analysis of plant C‐values is described. This work indicates that the unusually large dynamic range of the C6, a design feature, coupled to the linearity of fluorescence emission conferred by staining of nuclei using propidium iodide, allows simultaneous analysis of species whose C‐values span that of almost the entire described angiosperms. © 2009 International Society for Advancement of Cytometry
Methodology significantly affects genome size estimates: Quantitative evidence using bryophytes

Flow cytometry (FCM) is commonly used to determine plant genome size estimates. Methodology has improved and changed during the past three decades, and researchers are encouraged to optimize protocols for their specific application. However, this step is typically omitted or undescribed in the current plant genome size literature, and this omission could have serious consequences for the genome size estimates obtained. Using four bryophyte species (Brachythecium velutinum, Fissidens taxifolius, Hedwigia ciliata, and Thuidium minutulum), three methodological approaches to the use of FCM in plant genome size estimation were tested. These included nine different buffers (Baranyi's, de Laat's, Galbraith's, General Purpose, LB01, MgSO4, Otto's, Tris.MgCl2, and Woody Plant), seven propidium iodide (PI) staining periods (5, 10, 15, 20, 45, 60, and 120 min), and six PI concentrations (10, 25, 50, 100, 150, and 200 μg ml−1). Buffer, staining period and staining concentration all had a statistically significant effect (P = 0.05) on the genome size estimates obtained for all four species. Buffer choice and PI concentration had the greatest effect, altering the 1C‐values by as much as 8% and 14%, respectively. As well, the quality of the data varied with the different methodology used. Using the methodology determined to be the most accurate in this study (LB01 buffer and PI staining for 20 min at 150 μg ml−1), three new genome size estimates were obtained: B. velutinum: 0.46pg, H. ciliata: 0.30pg, and T. minutulum: 0.46pg. While the peak quality of flow cytometry histograms is important, researchers must consider that changes in methodology can also affect the relative peak positions and therefore the genome size estimates obtained for plants using FCM. © 2010 International Society for Advancement of Cytometry
Six global and local QSPR models of aqueous solubility at pH = 7.4 based on structural similarity and physicochemical descriptors

Abstract Aqueous solubility at pH = 7.4 is a very important property for medicinal chemists because this is the pH value of physiological media. The present work describes the application of three different methods (support vector machine (SVM), random forest (RF) and multiple linear regression (MLR)) and three local quantitative structure–property relationship (QSPR) models (regression corrected by nearest neighbours (RCNN), arithmetic mean property (AMP) and local regression property (LoReP)) to construct stable QSPRs with clear mechanistic interpretation. Our data set contained experimental values of aqueous solubility at pH = 7.4 of 387 chemicals (349 in the training set and 38 in the test set including 16 own measurements). The initial descriptor pool contained 210 physicochemical descriptors, calculated from the HYBOT, DRAGON, SYBYL and VolSurf+ programs. Six QSPRs with good statistics based on fundamentals of aqueous solubility and optimization of descriptor space were obtained. Those models have an RMSE close to experimental error (0.70), and are amenable to physical interpretation. The QSPR models developed in this study may be useful for medicinal chemists. Global MLR, RF and SVM models may be valuable for consideration of common factors that influence solubility. The RCNN, AMP and LoReP local models may be helpful for the optimization of aqueous solubility in small sets of related chemicals.
Impact of 7‐ketocholesterol and very long chain fatty acids on oligodendrocyte lipid membrane organization: Evaluation via LAURDAN and FAMIS spectral image analysis

In the context of multiple sclerosis and X‐linked adrenoleukodystrophy, 7‐ketocholesterol (7KC) and very long chain fatty acids (C24:0, C26:0) are supposed to induce side effects respectively on oligodendrocytes which are myelin (which is a lipoproteic complex) synthesizing cells. The effects of 7KC (25, 50 μM), C24:0 and C26:0 (10, 20 μM) on cell viability and lipid membrane organization were investigated on 158N murine oligodendrocytes. Concerning 7KC and fatty acids (at 20 μM only): 1) cell growth was strongly inhibited; 2) marked induction of cell death was revealed with propidium iodide (PI); 3) no apoptotic cells were found with C24:0 and C26:0 (absence of cells with condensed and/or fragmented nuclei, of FLICA positive cells and of PI negative/SYTO16 negative cells); 4) some apoptotic cells were detected with 7KC. Fatty acids (at 20 μM only) and 7KC also induced a disorganization of lipid membranes revealed with Merocyanine 540. So, to point out the effects of 7KC (25 μM), C24:0 and C26:0 (20 μM) on the lateral organization of lipid membranes, we used LAURDAN, which gives simultaneous information about morphology and phase state of lipid domains: its emission is blue in the ordered lipid phase, green in the disordered lipid phase. To overcome the qualitative filtering settings of blue and green emission colors, data obtained by mono‐ and bi‐photon confocal microscopy were analyzed by spectral analysis. Sequences of emission images were obtained on both mono‐ and bi‐photon confocal microscopes and processed by means of Factor Analysis of Medical Image Sequences (FAMIS), which is a relevant tool to unmix emission spectra and provide pure color images. Only 7KC was capable to induce a green emission with LAURDAN. Thus, at concentrations inducing oligodendrocyte cell death, 7KC (25 μM) is more efficient than C24:0 and C26:0 (20 μM), to trigger lateral lipid membrane disorganization. © 2011 International Society for Advancement of Cytometry