Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene fitness landscape of group A streptococcus during necrotizing myositis

Necrotizing fasciitis and myositis are devastating infections characterized by high mortality. Group A streptococcus (GAS) is a common cause of these infections, but the molecular pathogenesis is poorly understood. We report a genome-wide analysis using serotype M1 and M28 strains that identified novel GAS genes contributing to necrotizing myositis in nonhuman primates (NHP), a clinically relevant model. Using transposon directed insertion-site sequencing (TraDIS) we identified 126 and 116 GAS genes required for infection by serotype M1 and M28 organisms, respectively. For both M1 and M28 strains, more than 25% of the GAS genes required for necrotizing myositis encode known or putative transporters. Thirteen GAS transporters contributed to both M1 and M28 strain fitness in NHP myositis, including putative importers for amino acids, carbohydrates, and vitamins, and exporters for toxins, quorum sensing peptides, and uncharacterized molecules. Targeted deletion of genes encoding five transporters confirmed that each isogenic mutant strain was significantly impaired in causing necrotizing myositis in NHPs. qRT-PCR analysis showed that these five genes are expressed in infected NHP and human skeletal muscle. Certain substrate-binding lipoproteins of these transporters, such as Spy0271 and Spy1728, were previously documented to be surface-exposed, suggesting that our findings have translational research implications.
New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function/Dysfunction in Cardiovascular Disease

The Global Burden of Disease Study identified cardiovascular risk factors as leading causes of global deaths and life years lost. Endothelial dysfunction represents a pathomechanism that is associated with most of these risk factors and stressors, and represents an early (subclinical) marker/predictor of atherosclerosis. Oxidative stress is a trigger of endothelial dysfunction and it is a hall-mark of cardiovascular diseases and of the risk factors/stressors that are responsible for their initiation. Endothelial function is largely based on endothelial nitric oxide synthase (eNOS) function and activity. Likewise, oxidative stress can lead to the loss of eNOS activity or even “uncoupling” of the enzyme by adverse regulation of well-defined “redox switches” in eNOS itself or up-/down-stream signaling molecules. Of note, not only eNOS function and activity in the endothelium are essential for vascular integrity and homeostasis, but also eNOS in perivascular adipose tissue plays an important role for these processes. Accordingly, eNOS protein represents an attractive therapeutic target that, so far, was not pharmacologically exploited. With our present work, we want to provide an overview on recent advances and future therapeutic strategies that could be used to target eNOS activity and function in cardiovascular (and other) diseases, including life style changes and epigenetic modulations. We highlight the redox-regulatory mechanisms in eNOS function and up- and down-stream signaling pathways (e.g., tetrahydrobiopterin metabolism and soluble guanylyl cyclase/cGMP pathway) and their potential pharmacological exploitation.
Repeated Sequential Action by Young Children: Developmental Changes in Representational Flexibility of Task Context

A wealth of developmental research suggests that preschoolers are capable of reporting, imitating, and performing sequential actions they engage in routinely. However, few studies have explored the developmental and cognitive mechanisms required for learning how to perform such routines. A previous computational model of routines argued that a representation of task contexts underlying routines could change flexibly. This position was supported by the empirical evidence that if adults are interrupted in the course of a routine, they make fewer errors if they are interrupted just before the selection of context-dependent action than if they are interrupted earlier. Another computational model examined how efficiently adults learned to perform routines and suggested the relationship of learning efficacy with executive functions. The present study aimed to examine whether the above-mentioned models and evidence from adults can be extended to preschoolers by using an experimental task, in which children were required to play the role of a baker and repeatedly make toast for either a cat or mouse, with momentary distractions. Experiment 1 showed that earlier interruption tended to cause older children to produce more branch point errors than interruption immediately before the branch points, whereas younger children tended to be vulnerable to both interruptions. Further, across 2 experiments, this study showed that the developmental differences in how young children represent task contexts were associated with their executive functions. These findings indicate that the representational flexibility of task contexts underlies children’s performance of repeated sequential actions and its association with executive functions.
Comorbidity, Frailty, and Waitlist Mortality among Kidney Transplant Candidates of All Ages

Background: Kidney transplantation (KT) candidates often present with multiple comorbidities. These patients also have a substantial burden of frailty, which is also associated with increased mortality. However, it is unknown if frailty is merely a surrogate for comorbidity, itself an independent domain of risk, or if frailty and comorbidity have differential effects. Better understanding the interplay between these 2 constructs will improve clinical decision making in KT candidates. Objective: To test whether comorbidity is equally associated with waitlist mortality among frail and nonfrail KT candidates and to test whether measuring both comorbidity burden and frailty improves mortality risk prediction. Methods: We studied 2,086 candidates on the KT waitlist (November 2009 – October 2017) in a multicenter cohort study, in whom frailty and comorbidity were measured at evaluation. We quantified the association between Charlson comorbidity index (CCI) adapted for end-stage renal disease and waitlist mortality using an adjusted Cox proportional hazards model and tested whether this association differed between frail and nonfrail candidates. Results: At evaluation, 18.1% of KT candidates were frail and 51% had a high comorbidity burden (CCI score ≥2). Candidates with a high comorbidity burden were at 1.38-fold (95% CI 1.01–1.89) increased risk of waitlist mortality. However, this association differed by frailty status (p for interaction = 0.01): among nonfrail candidates, a high comorbidity burden was associated with a 1.66-fold (95% CI 1.17–2.35) increased mortality risk; among frail candidates, here was no statistically significant association (HR 0.75, 95% CI 0.44–1.29). Adding this interaction between comorbidity and frailty to a mortality risk estimation model significantly improved prediction, increasing the c-statistic from 0.640 to 0.656 (p < 0.001). Conclusions: Nonfrail candidates with a high comorbidity burden at KT evaluation have an increased risk of waitlist mortality. Importantly, comorbidity is less of a concern in already high-risk patients who are frail.
Dietary and circulating vitamin C, vitamin E, β-carotene and risk of total cardiovascular mortality: a systematic review and dose–response meta-analysis of prospective observational studies

Abstract Objective The present review aimed to quantify the association of dietary intake and circulating concentration of major dietary antioxidants with risk of total CVD mortality. Design Systematic review and meta-analysis. Setting Systematic search in PubMed and Scopus, up to October 2017. Participants Prospective observational studies reporting risk estimates of CVD mortality across three or more categories of dietary intakes and/or circulating concentrations of vitamin C, vitamin E and β-carotene were included. A random-effects meta-analysis was conducted. Results A total of fifteen prospective cohort studies and three prospective evaluations within interventional studies (320 548 participants and 16 974 cases) were analysed. The relative risks of CVD mortality for the highest v. the lowest category of antioxidant intakes were as follows: vitamin C, 0·79 (95 % CI 0·68, 0·89; I 2=46 %, n 10); vitamin E, 0·91 (95 % CI 0·79, 1·03; I 2=51 %, n 8); β-carotene, 0·89 (95 % CI 0·73, 1·05; I 2=34 %, n 4). The relative risks for circulating concentrations were: vitamin C, 0·60 (95 % CI 0·42, 0·78; I 2=65 %, n 6); α-tocopherol, 0·82 (95 % CI 0·76, 0·88; I 2=0 %, n 5); β-carotene, 0·68 (95 % CI 0·52, 0·83; I 2=50 %, n 6). Dose–response meta-analyses demonstrated that the circulating biomarkers of antioxidants were more strongly associated with risk of CVD mortality than dietary intakes. Conclusions The present meta-analysis demonstrates that higher vitamin C intake and higher circulating concentrations of vitamin C, vitamin E and β-carotene are associated with a lower risk of CVD mortality.
Association Rule-Based Novel Incremental Updating Algorithm

This paper focuses on an important research topic in data mining (DM) which heavily replies on the association rules. In order to deal with the maintenance issues within the background of the static transaction database, there are some minor changes to minimum support and confidence coefficient. A novel algorithm based on incremental updated is proposed, which is termed as NIUA (Novel Incremental Updating Algorithm). IUA uses association rules to mining the database, aiming at finding the potential information or finding the reasons from massive data.
A Mechanism‐Based Population Pharmacokinetics Model of Erythropoietin in Premature Infants and Healthy Adults Following Multiple Intravenous Doses

The objective of the current study was to develop a population pharmacokinetics (PK) model for erythropoietin (Epo) in premature infants and healthy adults to characterize the variation in PK, and to study the differences in Epo PK in these 2 populations. Thirteen very low‐birth‐weight premature infants (<1500 g at birth), and 10 healthy adults received up to 4 intravenous doses of Epo that ranged from 10 to 500 U/kg. The final model had a target‐mediated saturable, nonlinear, elimination pathway that incorporated the mechanism of Epo binding to its receptors along with a parallel linear, central elimination pathway. Epo clearance was found to be significantly higher in preterm infants compared to adults. Epo clearance via the nonlinear pathway was found to be much higher in infants; they had an Epo receptor capacity of 133 pM vs 86.6 pM in adults, which is most likely due to the higher erythroid progenitor cell mass per kilogram of body weight in infants. The parallel linear elimination was found to be more dominant in adults, reaching 91% of the total clearance with a 500‐U/kg dose compared to just 6.1% of the total clearance following the same dose in preterm infants. Thus, this mechanism‐based population PK model revealed that receptor‐based nonlinear elimination is the dominant Epo elimination pathway in premature infants, and parallel linear elimination is dominant in adults.
Risk of post‐traumatic knee osteoarthritis after knee injury in military service members

PURPOSE The aims of the present study were: (a) to identify the incidence of osteoarthritis (OA) after a traumatic knee injury; (b) identify the risk of post-traumatic osteoarthritis (PTOA) based on the type of injury; and (c) identify the time from injury to OA diagnosis. PATIENTS AND METHODS The Expeditionary Medical Encounter Database, containing healthcare utilization for all deployment injuries sustained by military service members, was queried for traumatic knee injuries between 2001 and 2016. Subsequent diagnosis of knee OA was identified, defined as PTOA. Time to knee PTOA diagnosis was determined and logistic regression was used to obtain odds ratios (ORs) (95% confidence interval [CI]) between knee injury type and development of PTOA. RESULTS A total of 345 (9.57%) of the 3,605 subjects were diagnosed with PTOA. The median time to diagnosis was 4.10 years. Four primary diagnoses remained significantly associated with PTOA after adjusting for age and injury severity score: fracture (adjusted OR [aOR] = 1.36; 95% CI 1.02, 1.82), sprain (aOR = 1.59; 95% CI 1.23, 2.06), dislocation (aOR = 3.70; 95% CI 2.09, 6.55) and derangement (aOR = 2.38; 95% CI 1.33, 4.28). Subjects were significantly less likely to develop PTOA after a soft-tissue injury (aOR = 0.44; 95% CI 0.41, 0.75). CONCLUSIONS A substantial number of individuals with a traumatic knee injury developed early PTOA (9.6%). Certain knee injuries have a greater association with PTOA. Future studies should implement longer surveillance periods and identify other healthcare variables associated with the risk of developing PTOA, to include appropriate and timely interventions.
Non-Destructive Trace Detection of Explosives Using Pushbroom Scanning Hyperspectral Imaging System

The aim of this study was to investigate the potential of the non-destructive hyperspectral imaging system (HSI) and accuracy of the model developed using Support Vector Machine (SVM) for determining trace detection of explosives. Raman spectroscopy has been used in similar studies, but no study has been published which is based on measurement of reflectance from hyperspectral sensor for trace detection of explosives. HSI used in this study has an advantage over existing techniques due to its combination of imaging system and spectroscopy, along with being contactless and non-destructive in nature. Hyperspectral images of the chemical were collected using the BaySpec hyperspectral sensor which operated in the spectral range of 400–1000 nm (144 bands). Image processing was applied on the acquired hyperspectral image to select the region of interest (ROI) and to extract the spectral reflectance of the chemicals which were stored as spectral library. Principal Component Analysis (PCA) and first derivative was applied to reduce the high dimensionality of the image and to determine the optimal wavelengths between 400 and 1000 nm. In total, 22 out of 144 wavelengths were selected by analysing the loadings of principal components (PC). SVM was used to develop the classification model. SVM model established on the whole spectrum from 400 to 1000 nm achieved an accuracy of 81.11%, whereas an accuracy of 77.17% with less computational load was achieved when SVM model was established on the optimal wavelengths selected. The results of the study demonstrate that the hyperspectral imaging system along with SVM is a promising tool for trace detection of explosives.
‘Good health’ as a barrier and facilitator to ART initiation: a qualitative study in the era of test-and-treat in Mozambique

Abstract HIV test-and-treat programmes are being implemented throughout sub-Saharan Africa, enrolling HIV-positive clients into antiretroviral treatment (ART) immediately after diagnosis, regardless of clinical stage or CD4 count. This study conducted in Mozambique examined what influenced clients who tested HIV-positive in the context of test-and-treat to make ART initiation decisions. Eighty in-depth interviews with HIV-positive clients and nine focus group discussions with health care workers were completed across 10 health facilities. ‘Good health’ acted simultaneously as a barrier and facilitator; clients in good health often found a positive HIV diagnosis hard to cope with since HIV was traditionally associated with ill health. Concerns about ART side effects, fear of inadvertent HIV status disclosure and discrimination, limited privacy at health facilities and long waiting times were also barriers to initiation. In contrast, being in good health also acted as a motivator to start treatment so as to remain healthy, maintain responsibilities such as work and caring for dependents and avoid unwanted disclosure. Study findings offer an in-depth understanding of the complex dynamics between individual perceptions of ‘being healthy’ and its influence on ART initiation within the context of test-and-treat programme implementation.
A finite mixture model for X‐chromosome association with an emphasis on microbiome data analysis

Analysis of the X chromosome has been largely neglected in genetic studies mainly because of complex underlying biological mechanisms. On the other hand, the study of human microbiome data (typically over‐dispersed counts with an excess of zeros) has generated great interest recently because of advancements in next‐generation sequencing technologies. We propose a novel approach to infer the association between host genetic variants in the X‐chromosome and microbiome data. The method accounts for random X‐chromosome inactivation (XCI), skewed (or nonrandom) XCI (XCI‐S), and escape of XCI (XCI‐E). The inference is performed through a finite mixture model (FMM), in which an indicator variable denoting the “true” biological mechanism is treated as missing data. An expectation‐maximization algorithm on zero‐inflated and two‐part models is implemented to estimate genetic effects. We investigate the performance of the FMM along with strategies that assume XCI and XCI‐E mechanisms for all subjects compared with alternative approaches. Briefly, an XCI mechanism codes males’ genotypes as homozygous females, whereas under XCI‐E, males are treated as heterozygous females. By comprehensive simulations, we evaluate tests of the hypothesis under a computationally efficient score statistic. In summary, the FMM renders reduced bias and commensurate power compared to XCI, XCI‐E, and alternative strategies while maintaining adequate Type 1 error control. The proposed method has far‐reaching applications. In particular, we illustrate its usage on a large‐scale human microbiome study, the Genetic, Environmental and Microbial (GEM) project, to test for the genetic association on the X chromosome.
Un classifieur du comportement des utilisateurs dans les applications pair-à-pair de streaming vidéo

Depuis quelques annees, les applications de streaming video pair-a-pair sont devenues de plus en plus populaires. Cependant, ces systemes souffrent toujours de problemes de performance, notamment du fait que, comme les pairs dependent les un des autres, leur comportement individuel a une influence directe sur le reseau. Pour cette raison, l'etude du comportement des utilisateurs est necessaire pour definir des mecanismes de controle adaptatifs. D'importantes campagnes de mesure s ont ete realisees afin d'identifier un comportement moyen conduisant a un modele general des utilisateurs. Toutefois, le comportement individuel ne suit pas necessairement le comportement global et les modeles globaux ne sont pas a meme de traiter des utilisateurs ayant des habitudes, des preferences et des comportements differents. Nous proposons de tels modeles inspires de personnages de fictions et nous proposons un classifieur bayesien permettant a un pair de savoir quel modele lui correspond a partir d'observations. P2P-based live video streaming has become popular in recent years. Nevertheless, these systems still suffer from some performance problems such as the fact that, since peers depend upon each other, activities of users have a direct impact over these systems. Therefore, studying the user behavior is needed to design adaptive constrol mechanisms. Several intensive measurem ent studies have been performed over them in order to provide insights into an average user behavior that can be used for deducing a generalized model. However, the individual user behavior does not necessarily follow the global behavior and a global model is not suitable for dealing with users having different preferences, interests, habits and behaviors. We propose such models of users inspired from fictional characters who represent different kind of consistent behaviors, and we propose a Bayesian classifier that allows a peer to predict in which cla ss it is through simple observations.
NIR spectrophotometric system based on a conventional CCD camera

The near infrared spectral region (NIR) is useful in many applications. These include agriculture, the food and chemical industry, and textile and medical applications. In this region, spectral reflectance measurements are currently made with conventional spectrophotometers. These instruments are expensive since they use a diffraction grating to obtain monochromatic light. In this work, we present a multispectral imaging based technique for obtaining the reflectance spectra of samples in the NIR region (800 - 1000 nm), using a small number of measurements taken through different channels of a conventional CCD camera. We used methods based on the Wiener estimation, non-linear methods and principal component analysis (PCA) to reconstruct the spectral reflectance. We also analyzed, by numerical simulation, the number and shape of the filters that need to be used in order to obtain good spectral reconstructions. We obtained the reflectance spectra of a set of 30 spectral curves using a minimum of 2 and a maximum of 6 filters under the influence of two different halogen lamps with color temperatures Tc1 = 2852K and Tc2 = 3371K. The results obtained show that using between three and five filters with a large spectral bandwidth (FWHM = 60 nm), the reconstructed spectral reflectance of the samples was very similar to that of the original spectrum. The small amount of errors in the spectral reconstruction shows the potential of this method for reconstructing spectral reflectances in the NIR range.
The effects of Nigella sativa on quality of life, disease activity index, and some of inflammatory and oxidative stress factors in patients with ulcerative colitis

The aim of this study was to evaluate the effects of Nigella sativa (NS) supplementation in patients with ulcerative colitis. Two grams of NS powder or placebo were consumed for 6 weeks by 46 patients with active mild to moderate ulcerative colitis. Using valid and common questionnaires of colitis severity and blood sampling, we estimated disease activity index, quality of life, and some of inflammatory and oxidative stress factors at baseline and after 6 weeks of supplementation. NS‐elevated tumor necrosis factor‐alpha and high‐sensitivity‐c‐reactive‐protein as well as reduced malondialdehyde (p = 0.01, p = 0.02, and p = 0.005, respectively) compared with placebo. There was no significant difference between the two groups in serum total antioxidant capacity and nuclear factor kB levels. Total scores of Simple Clinical Colitis Activity Index Questionnaire and Inflammatory Bowel Disease Questionnaire‐9 were not different between the two groups; however, stool frequency score decreased significantly in NS group. Further clinical trials with different pattern of NS administration (the amount of total and divided daily doses, either powder type or standard extracts/oil and different time arrangement) are needed to clarify the vision.