Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Diagnostics for Lassa Fever at Irrua Specialist Teaching Hospital, Nigeria: Lessons Learnt from Two Years of Laboratory Operation

Background Lassa fever is a viral hemorrhagic fever endemic in West Africa. However, none of the hospitals in the endemic areas of Nigeria has the capacity to perform Lassa virus diagnostics. Case identification and management solely relies on non-specific clinical criteria. The Irrua Specialist Teaching Hospital (ISTH) in the central senatorial district of Edo State struggled with this challenge for many years. Methodology/Principal Findings A laboratory for molecular diagnosis of Lassa fever, complying with basic standards of diagnostic PCR facilities, was established at ISTH in 2008. During 2009 through 2010, samples of 1,650 suspected cases were processed, of which 198 (12%) tested positive by Lassa virus RT-PCR. No remarkable demographic differences were observed between PCR-positive and negative patients. The case fatality rate for Lassa fever was 31%. Nearly two thirds of confirmed cases attended the emergency departments of ISTH. The time window for therapeutic intervention was extremely short, as 50% of the fatal cases died within 2 days of hospitalization—often before ribavirin treatment could be commenced. Fatal Lassa fever cases were older (p = 0.005), had lower body temperature (p<0.0001), and had higher creatinine (p<0.0001) and blood urea levels (p<0.0001) than survivors. Lassa fever incidence in the hospital followed a seasonal pattern with a peak between November and March. Lassa virus sequences obtained from the patients originating from Edo State formed—within lineage II—a separate clade that could be further subdivided into three clusters. Conclusions/Significance Lassa fever case management was improved at a tertiary health institution in Nigeria through establishment of a laboratory for routine diagnostics of Lassa virus. Data collected in two years of operation demonstrate that Lassa fever is a serious public health problem in Edo State and reveal new insights into the disease in hospitalized patients.
The iso-response method: measuring neuronal stimulus integration with closed-loop experiments

Throughout the nervous system, neurons integrate high-dimensional input streams and transform them into an output of their own. This integration of incoming signals involves filtering processes and complex non-linear operations. The shapes of these filters and non-linearities determine the computational features of single neurons and their functional roles within larger networks. A detailed characterization of signal integration is thus a central ingredient to understanding information processing in neural circuits. Conventional methods for measuring single-neuron response properties, such as reverse correlation, however, are often limited by the implicit assumption that stimulus integration occurs in a linear fashion. Here, we review a conceptual and experimental alternative that is based on exploring the space of those sensory stimuli that result in the same neural output. As demonstrated by recent results in the auditory and visual system, such iso-response stimuli can be used to identify the non-linearities relevant for stimulus integration, disentangle consecutive neural processing steps, and determine their characteristics with unprecedented precision. Automated closed-loop experiments are crucial for this advance, allowing rapid search strategies for identifying iso-response stimuli during experiments. Prime targets for the method are feed-forward neural signaling chains in sensory systems, but the method has also been successfully applied to feedback systems. Depending on the specific question, “iso-response” may refer to a predefined firing rate, single-spike probability, first-spike latency, or other output measures. Examples from different studies show that substantial progress in understanding neural dynamics and coding can be achieved once rapid online data analysis and stimulus generation, adaptive sampling, and computational modeling are tightly integrated into experiments.
Comparative analysis of initial vocalizations of preterm and full-term infants with and without risk for development.

Purpose To compare the evolution of vocalization in preterm and full-term infants, with and without risk for development, analyzing the possible association of sociodemographic, obstetric and psychosocial variables with vocalization. Methods The study sample consisted of 30 infants, aged 3 months and 1 day to 4 months and 29 days (Phase 1) and 6 months and 1 day to 7 months and 29 days (Phase 2), of both genders, with gestational age <37 weeks (preterm group) and >37 weeks (full-term group). The following instruments were used for data collection: Child Development Risk Indicators (IRDl), the Denver II Test, an interview on the experience of motherhood with sociodemographic, obstetric and psychosocial data, as well as filming of the mother-infant dyad at the two phases of the research. Footage was analyzed using the EUDICO Linguistic Annotator (ELAN) software and the results were statistically analyzed on the STATISTICA 9.0 software. Results The larger the total number of Phase II infants' and mothers' vocalizations using motherese, the greater the number of IRDls present. Significant increase in vocalizations without motherese was also observed in Phase 2. Sociodemographic variables, gestational age, weight at birth, maternal schooling, and the Brazil Criterion did not directly affect the infants' vocalization level. Conclusion Analysis of the infants' vocalizations was sensitive to risk development and Child Development Risk Indicators in Phase 1; the Denver-language test was more effective in Phase 2. No influence of the sociodemographic variables was observed in the phases studied.
Pulmonary , gastrointestinal and urogenital pharmacology An antioxidant Trolox restores decreased oral absorption of cyclosporine A after liver ischemia – reperfusion through distinct mechanisms between CYP 3 A and P-glycoprotein in the small intestine

Oxidative stress is a critical mediator of various injuries following ischemia–reperfusion (I/R) associated with organ transplantation. Although oral bioavailability of cyclosporine A (CsA) was decreased by increased first-pass metabolism through CYP3A and P-glycoprotein (P-gp) specifically in the upper small intestine after liver I/R, the mechanism responsible for them remained to be clarified. In the present study, the effect of Trolox (an a-tocopherol analogue) on the decreased oral absorption of CsA through elevated intestinal CYP3A and P-gp after liver I/R and their regulations were investigated. Rats were subjected to 60 min of liver ischemia followed by 12 h of reperfusion. Trolox was administered intravenously 5 min before reperfusion. Trolox diminished the increased malondialdehyde and total glutathione levels in plasma by liver I/R and concomitantly prevented the decreased area under the blood concentration-time curve of orally administered CsA as well as initial absorption rate of CsA from upper small intestine. The elevated CYP3A mRNA and activity in the upper small intestine as well as expression levels of P-gp in upper, middle, and lower small intestines after liver I/R were attenuated by Trolox administration. The elevations of CYP3A levels specifically in the upper small intestine of I/R rats were correlated with the lithocholic acid levels in the bile. These results demonstrate that Trolox ameliorates the decreased oral absorption of CsA through elevated intestinal CYP3A and P-gp by preventing oxidative stress, where the biliary lithocholic acid may be responsible for the elevated transcription of CYP3A specifically in the upper small intestine after liver I/R. & 2012 Elsevier B.V. All rights reserved.
Beyond subjective and objective in statistics

Decisions in statistical data analysis are often justified, criticized or avoided by using concepts of objectivity and subjectivity. We argue that the words ‘objective’ and ‘subjective’ in statistics discourse are used in a mostly unhelpful way, and we propose to replace each of them with broader collections of attributes, with objectivity replaced by transparency, consensus, impartiality and correspondence to observable reality, and subjectivity replaced by awareness of multiple perspectives and context dependence. Together with stability, these make up a collection of virtues that we think is helpful in discussions of statistical foundations and practice. The advantage of these reformulations is that the replacement terms do not oppose each other and that they give more specific guidance about what statistical science strives to achieve. Instead of debating over whether a given statistical method is subjective or objective (or normatively debating the relative merits of subjectivity and objectivity in statistical practice), we can recognize desirable attributes such as transparency and acknowledgement of multiple perspectives as complementary goals. We demonstrate the implications of our proposal with recent applied examples from pharmacology, election polling and socio‐economic stratification. The aim of the paper is to push users and developers of statistical methods towards more effective use of diverse sources of information and more open acknowledgement of assumptions and goals.
Inhibition of Glycogen Synthase Kinase 3β Ameliorates D-GalN/LPS-Induced Liver Injury by Reducing Endoplasmic Reticulum Stress-Triggered Apoptosis

Background Glycogen synthase kinase 3β(GSK3β) is a ubiquitous serine-threonine protein kinase that participates in numerous cellular processes and disease pathophysiology. We aimed to determine therapeutic potential of GSK3β inhibition and its mechanism in a well-characterized model of lipopolysaccharide (LPS)-induced model of acute liver failure (ALF). Methodology In a murine ALF model induced by D-GalN(700 mg/kg)/LPS(10 µg/kg), we analyzed GSK3β mechanisms using a specific chemical inhibitor, SB216763, and detected the role of endoplasmic reticulum stress (ERS). Mice were administered SB216763 at 2 h before or after D-GalN/LPS injection, respectively, and then sacrificed 6 h after D-GalN/LPS treatment to evaluate its prophylactic and therapeutic function. The lethality rate, liver damage, ERS, cytokine expression, MAP kinase, hepatocyte apoptosis and expression of TLR 4 were evaluated, respectively. Whether the inhibition of GSK3β activation protected hepatocyte from ERS-induced apoptosis was investigated in vitro. Principal Findings GSK3β became quickly activated (dephosphorylated) upon D-GalN/LPS exposure. Administration of SB216763 not only ameliorated liver injury, as evidenced by reduced transaminase levels, and well-preserved liver architecture, but also decreased lethality. Moreover, GSK3β inhibition resulted in down-regulation of pro-apoptotic proteins C/EBP–homologous protein(CHOP) and caspase-12, which are related to ERS. To further demonstrate the role of ERS, we found that GSK3β inhibition protected hepatocyte from ERS-induced cell death. GSK3β inhibition down-regulated the MAPK pathways, reduced expression of inflammatory cytokines and decreased expression of TLR4. Conclusions Our findings demonstrate the key function of GSK3β signaling in the pathophysiology of ALF, especially in regulating the ERS, and provide a rationale for targeting GSK3β as a potential therapeutic strategy to ameliorate ALF.
Impact des variations de la mousson Africaine sur l’érosion chimique des silicates dans le bassin versant du Nil depuis 100.000 ans

L’objectif de cette these est de determiner une reconstruction de l’alteration continentale dans le bassin du Nil depuis 100.000 ans, afin de mieux comprendre l’impact des variations climatiques sur les sols, les apports a la Mediterranee et le cycle du carbone. Ce travail repose sur une etude geochimique fine des argiles extraites d’archives sedimentaires du delta du Nil sur une echelle de temps de 100.000 ans. Il repose sur une approche inedite du couplage d’un traceur de source (isotopes du neodyme) et de traceurs d’alterations (isotopes du lithium). Les resultats de cette etude mettent en evidence une reponse rapide de l’alteration continentale aux variations hydro-climatique en Afrique du Nord. De plus, les changements climatiques en Atlantique Nord et du ralentissement de l’AMOC ont eu une influence importante sur la diminution de l’intensite d’alteration continentale dans le bassin du Nil. A l’actuel, les taux d’alteration, et la consommation de CO2 associee, des trapps d’Ethiopie sont relativement faibles par rapport aux autres regions basaltiques. Nos resultats montrent cependant que durant l’African Humid Period, la consommation de CO2 dans cette region etait 2 a 3 fois plus importante qu’aujourd’hui. Cela indique que les trapps d’Ethiopie ont pu jouer un role non negligeable dans le cycle du CO2, et en particulier lors des periodes de fort runoff. Enfin, des developpements analytiques ont ete realises afin de pouvoir exploiter les compositions isotopiques en lithium des carbonates biogeniques marins, comme nouveaux traceurs des apports en eau douce du Nil. Les resultats obtenus suggerent une influence des effets dits « vitaux » et des processus de diagenese.
Multiple cytokines and chemokines are associated with rheumatoid arthritis-related autoimmunity in first-degree relatives without rheumatoid arthritis: Studies of the Aetiology of Rheumatoid Arthritis (SERA)

Objective We investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with systemic inflammation in a prospective cohort of first-degree relatives (FDRs) of RA probands, a population without RA but at increased risk for its future development. Methods We studied 44 autoantibody positive FDRs, of whom 29 were rheumatoid factor (RF) positive, 25 were positive for the high risk autoantibody profile (HRP), that is, positive for anti-cyclic citrullinated peptide and/or for at least two RF IgM, IgG or IgA isotypes, and nine FDRs who were positive for both; and 62 FDRs who were never autoantibody positive. Twenty-five cytokines/chemokines were measured using a bead-based assay in serum. As a comprehensive measure of inflammation, we calculated a Cytokine Score by summing all cytokine/chemokine levels, weighted by their regression coefficients for RA-autoantibody association. We compared C-reactive protein, individual cytokines/chemokines and Cytokine Score to the outcomes: positivity for RF and for the HRP using logistic regression. Results Adjusting for age, sex, ethnicity and ever smoking, the Cytokine Score and levels of IL-6 and IL-9 were associated with both RF and HRP. IL-2, granulocyte macrophage-colony stimulating factor (GM-CSF), and interferon (IFN)-γ were associated with HRP only. Associations between the Cytokine Score and RF and HRP positivity were replicated in an independent military personnel cohort. Conclusions In first-degree relatives of patients with RA, RA-related autoimmunity is associated with inflammation, as evidenced by associations with multiple cytokines and chemokines.
Tevatron Combination of Single-Top-Quark Cross Sections and Determination of the Magnitude of the Cabibbo-Kobayashi-Maskawa Matrix Element V_{tb}.

We present the final combination of CDF and D0 measurements of cross sections for single-top-quark production in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7 fb^{-1} per experiment. The t-channel cross section is measured to be σ_{t}=2. 25_{-0.31}^{+0.29} pb. We also present the combinations of the two-dimensional measurements of the s- vs t-channel cross section. In addition, we give the combination of the s+t channel cross section measurement resulting in σ_{s+t}=3. 30_{-0.40}^{+0.52} pb, without assuming the standard model value for the ratio σ_{s}/σ_{t}. The resulting value of the magnitude of the top-to-bottom quark coupling is |V_{tb}|=1. 02_{-0.05}^{+0.06}, corresponding to |V_{tb}|>0.92 at the 95% C.L.
Interplay between Constraints, Objectives, and Optimality for Genome-Scale Stoichiometric Models

High-throughput data generation and genome-scale stoichiometric models have greatly facilitated the comprehensive study of metabolic networks. The computation of all feasible metabolic routes with these models, given stoichiometric, thermodynamic, and steady-state constraints, provides important insights into the metabolic capacities of a cell. How the feasible metabolic routes emerge from the interplay between flux constraints, optimality objectives, and the entire metabolic network of a cell is, however, only partially understood. We show how optimal metabolic routes, resulting from flux balance analysis computations, arise out of elementary flux modes, constraints, and optimization objectives. We illustrate our findings with a genome-scale stoichiometric model of Escherichia coli metabolism. In the case of one flux constraint, all feasible optimal flux routes can be derived from elementary flux modes alone. We found up to 120 million of such optimal elementary flux modes. We introduce a new computational method to compute the corner points of the optimal solution space fast and efficiently. Optimal flux routes no longer depend exclusively on elementary flux modes when we impose additional constraints; new optimal metabolic routes arise out of combinations of elementary flux modes. The solution space of feasible metabolic routes shrinks enormously when additional objectives---e.g. those related to pathway expression costs or pathway length---are introduced. In many cases, only a single metabolic route remains that is both feasible and optimal. This paper contributes to reaching a complete topological understanding of the metabolic capacity of organisms in terms of metabolic flux routes, one that is most natural to biochemists and biotechnologists studying and engineering metabolism.
Pharmacodynamics and tolerability of repository corticotropin injection in healthy human subjects: A comparison with intravenous methylprednisolone

Repository corticotropin injection (porcine adrenocorticotropic hormone [ACTH] analog) and intravenous methylprednisolone (IVMP) are used to treat inflammatory conditions such as multiple sclerosis (MS) exacerbations and rheumatoid arthritis. This multiple‐dose, randomized, crossover, open‐label study evaluated and compared pharmacodynamic outcomes in subjects who received ACTH analog (80 U subcutaneously) or IVMP (1 g) daily for 5 days. Specific outcome measures included IVMP and cortisol concentrations, total cortisol‐equivalent exposure, immune cell population changes, and tolerability. IVMP and ACTH analog increased granulocyte numbers and decreased lymphocyte counts; effects on both were significantly less pronounced with ACTH analog. Based on total cortisol‐equivalent exposure (assuming linearity), administration of 80 U of ACTH analog equates to 30 mg IVMP. Because IVMP doses significantly higher than 30 mg are usually required to treat MS exacerbations, the lower cortisol‐equivalent exposure of 80 U ACTH analog supports the hypothesis that efficacy of ACTH analog results from both steroid‐dependent and ‐independent properties. Adverse events were mild in severity; subject incidence for adverse‐event reporting was similar following both regimens. The clinical relevance of these findings in autoimmune disease populations is unknown and requires further evaluation.
Detrimental Effects of Environmental Tobacco Smoke in Relation to Asthma Severity

Background Environmental tobacco smoke (ETS) has adverse effects on the health of asthmatics, however the harmful consequences of ETS in relation to asthma severity are unknown. Methods In a multicenter study of severe asthma, we assessed the impact of ETS exposure on morbidity, health care utilization and lung functions; and activity of systemic superoxide dismutase (SOD), a potential oxidative target of ETS that is negatively associated with asthma severity. Findings From 2002–2006, 654 asthmatics (non-severe 366, severe 288) were enrolled, among whom 109 non-severe and 67 severe asthmatics were routinely exposed to ETS as ascertained by history and validated by urine cotinine levels. ETS-exposure was associated with lower quality of life scores; greater rescue inhaler use; lower lung function; greater bronchodilator responsiveness; and greater risk for emergency room visits, hospitalization and intensive care unit admission. ETS-exposure was associated with lower levels of serum SOD activity, particularly in asthmatic women of African heritage. Interpretation ETS-exposure of asthmatic individuals is associated with worse lung function, higher acuity of exacerbations, more health care utilization, and greater bronchial hyperreactivity. The association of diminished systemic SOD activity to ETS exposure provides for the first time a specific oxidant mechanism by which ETS may adversely affect patients with asthma.
Detecting Prostatic Adenocarcinoma From Digitized Histology Using a Multi-Scale Hierarchical Classification Approach

In this paper we present a computer-aided diagnosis (CAD) system to automatically detect prostatic adenocarcinoma from high resolution digital histopathological slides. This is especially desirable considering the large number of tissue slides that are currently analyzed manually - a laborious and time-consuming task. Our methodology is novel in that texture-based classification is performed using a hierarchical classifier within a multi-scale framework. Pyramidal decomposition is used to reduce an image into its constituent scales. The cascaded image analysis across multiple scales is similar to the manner in which pathologists analyze histopathology. Nearly 600 different image texture features at multiple orientations are extracted at every pixel at each image scale. At each image scale the classifier only analyzes those image pixels that have been determined to be tumor at the preceding lower scale. Results of quantitative evaluation on 20 patient studies indicate (1) an overall accuracy of over 90% and (2) an approximate 8-fold savings in terms of computational time. Both the AdaBoost and decision tree classifiers were considered and in both cases tumor detection sensitivity was found to be relatively constant across different scales. Detection specificity was however found to increase at higher scales reflecting the availability of additional discriminatory information
Composition, anti-quorum sensing and antimicrobial activity of essential oils from Lippia alba

Many Gram-negative pathogens have the ability to produce N-acylhomoserine lactones (AHLs) as signal molecules for quorum sensing (QS). This cell-cell communication system allows them to coordinate gene expression and regulate virulence. Strategies to inhibit QS are promising for the control of infectious diseases or antibiotic resistant bacterial pathogens. The aim of the present study was to evaluate the anti-quorum sensing (anti-QS) and antibacterial potential of five essential oils isolated from Lippia alba on the Tn-5 mutant of Chromobacterium violaceum CV026, and on the growth of the gram-positive bacteria S. aureus ATCC 25923. The anti-QS activity was detected through the inhibition of the QS-controlled violacein pigment production by the sensor bacteria. Results showed that two essential oils from L. alba, one containing the greatest geranial:neral and the other the highest limonene:carvone concentrations, were the most effective QS inhibitors. Both oils also had small effects on cell growth. Moreover, the geranial/neral chemotype oil also produced the maximum zone of growth inhibition against S. aureus ATCC 25923. These data suggest essential oils from L. alba have promising properties as QS modulators, and present antibacterial activity on S. aureus.