Miracle-dz/UniFAR-FTUs huggingface dataset:
Modelling access to renal transplantation waiting list in a French healthcare network using a Bayesian method

Evaluation of adult candidates for kidney transplantation diverges from one centre to another. Our purpose was to assess the suitability of Bayesian method for describing the factors associated to registration on the waiting list in a French healthcare network. We have found no published paper using Bayesian method in this domain. Eight hundred and nine patients starting renal replacement therapy were included in the analysis. The data were extracted from the information system of the healthcare network. We performed conventional statistical analysis and data mining analysis using mainly Bayesian networks. The Bayesian model showed that the probability of registration on the waiting list is associated to age, cardiovascular disease, diabetes, serum albumin level, respiratory disease, physical impairment, follow-up in the department performing transplantation and past history of malignancy. These results are similar to conventional statistical method. The comparison between conventional analysis and data mining analysis showed us the contribution of the data mining method for sorting variables and having a global view of the variables' associations. Moreover theses approaches constitute an essential step toward a decisional information system for healthcare networks.
Virus‐neutralizing antibodies to hepatitis C virus

For a long time, the lack of an appropriate cell culture system has hampered the study of neutralizing antibody responses against hepatitis C virus (HCV). However, the last decade has seen the development of several model systems that have significantly advanced our understanding of viral entry and antibody neutralization. Studies of acutely infected patients suggest that a strong and early production of neutralizing antibodies may contribute to control the virus during the acute phase of HCV infection and facilitate viral elimination by cellular immune responses. It also emerges that the early antibody response mainly targets hypervariable region 1 (HVR1) of the envelope glycoprotein E2. This host response can lead to viral escape from neutralization by rapid amino acid changes in this hypervariable region. In contrast, cross‐reactive neutralizing antibodies seem to appear later during HCV infection, and several mechanisms contribute to reduce their accessibility to their cognate epitopes. These include the masking of major conserved neutralizing epitopes by HVR1, specific N‐linked glycans and the lipid moiety of the viral particle. Other potential mechanisms of evasion from the neutralizing antibody response include a modulation by high‐density lipoproteins and interfering antibodies as well as the capacity of the virus to be transferred by cell‐to‐cell contacts. Finally, the recent identification of several highly conserved neutralizing epitopes provides some opportunities for the design and development of vaccine candidates that elicit a protective humoral immune response.
Scarring, stem cells, scaffolds and skin repair

The treatment of full thickness skin loss, which can be extensive in the case of large burns, continues to represent a challenging clinical entity. This is due to an on‐going inability to produce a suitable tissue engineered substrate that can satisfactorily replicate the epidermal and dermal in vivo niches to fulfil both aesthetic and functional demands. The current gold standard treatment of autologous skin grafting is inadequate because of poor textural durability, scarring and associated contracture, and because of a paucity of donor sites in larger burns. Tissue engineering has seen exponential growth in recent years with a number of ‘off‐the‐shelf’ dermal and epidermal substitutes now available. Each has its own limitations. In this review, we examine normal wound repair in relation to stem/progenitor cells that are intimately involved in this process within the dermal niche. Endothelial precursors, in particular, are examined closely and their phenotype, morphology and enrichment from multiple sources are described in an attempt to provide some clarity regarding the controversy surrounding their classification and role in vasculogenesis. We also review the role of the next generation of cellularized scaffolds and smart biomaterials that attempt to improve the revascularisation of artificial grafts, the rate of wound healing and the final cosmetic and functional outcome. Copyright © 2013 John Wiley & Sons, Ltd.
Aetiological differences in neuroanatomy of the vegetative state: insights from diffusion tensor imaging and functional implications

Background An improved in vivo understanding of variations in neuropathology in the vegetative state (VS) may aid diagnosis, improve prognostication and help refine the selection of patients for particular treatment regimes. The authors have used diffusion tensor imaging (DTI) to characterise the extent and location of white matter loss in VS secondary to traumatic brain injury (TBI) and ischaemic–hypoxic injury. Methods Twelve patients with VS (seven TBI, five ischaemic/hypoxic injuries) underwent MRI including DTI at a minimum of 3 months postinjury. Mean apparent diffusion coefficient, fractional anisotropy and eigenvalues were obtained for whole-brain grey and white matter, the pons, thalamus, ventral midbrain, dorsal midbrain and the corpus callosum. DTI measures of supratentorial damage were compared with a summed measure from the JFK modified Coma Recovery Scale (CRS-R) and with a three-point scale of functional magnetic resonance imaging (fMRI) response to an auditory paradigm to assess whether residual integrity of supratentorial white matter connectivity correlated with cortical processing. Results Conventional radiological approaches did not detect lesions in regions where quantitative DTI demonstrated abnormalities. There was evidence of marked, broadly similar, abnormalities in the supratentorial grey- and white-matter compartments from both aetiologies. In contrast, discordant findings were found in the infratentorial compartment, with DTI abnormalities in the brainstem confined to the TBI group. Supratentorial DTI abnormalities correlated with the CRS-R as well as responses to an fMRI paradigm that detected convert cognitive processing. Conclusions DTI may help to characterise differences in patients in VS. These findings may have implications for response to therapies, and should be taken into account in trials of interventions aimed at arousal in VS.
Effects of adherence to treatment on short-term outcomes in children with juvenile idiopathic arthritis.

OBJECTIVE To determine the impact of adherence to treatment (medication and prescribed exercise) on outcomes in children with juvenile idiopathic arthritis (JIA). METHODS In this longitudinal study, we studied parents of patients with JIA at the Montreal Children's Hospital and British Columbia Children's Hospital in Vancouver. Adherence was evaluated on a visual analog scale in the Parent Adherence Report Questionnaire. Outcomes of interest were active joint count, pain, child functional score on the Child Health Assessment Questionnaire, quality of life score on the Juvenile Arthritis Quality of Life Questionnaire, and parental global impression of overall well-being. The association between adherence to treatment and subsequent outcomes was evaluated using generalized estimating equations and logistic regression. RESULTS Mean age and disease duration of our sample of 175 children were 10.2 and 4.1 years, respectively. Moderate adherence to medication was associated with lower active joint count (odds ratio [OR] 0.47, 95% confidence interval [95% CI] 0.22-0.99). Moderate adherence to exercise was associated with better functional score (OR 0.13, 95% CI 0.03-0.54), and lower pain during the last week (OR 0.14, 95% CI 0.04-0.50). Both high and moderate adherence to exercise were associated with parental perception of global improvement. CONCLUSION Improved outcomes in patients who adhered to treatment underscores the need for clinicians to address adherence issues with their patients. Sustaining adherence, particularly to the more time-consuming treatment of exercise, is a challenge.
A Nonstochastic Information Theory for Communication and State Estimation

In communications, unknown variables are usually modelled as random variables, and concepts such as independence, entropy and information are defined in terms of the underlying probability distributions. In contrast, control theory often treats uncertainties and disturbances as bounded unknowns having no statistical structure. The area of networked control combines both fields, raising the question of whether it is possible to construct meaningful analogues of stochastic concepts such as independence, Markovness, entropy and information without assuming a probability space. This paper introduces a framework for doing so, leading to the construction of a maximin information functional for nonstochastic variables. It is shown that the largest maximin information rate through a memoryless, error-prone channel in this framework coincides with the block-coding zero-error capacity of the channel. Maximin information is then used to derive tight conditions for uniformly estimating the state of a linear time-invariant system over such a channel, paralleling recent results of Matveev and Savkin.
Is There a Role for Surgery for Patients with a Complete Clinical Response after Chemoradiation for Esophageal Cancer? An Intention-to-Treat Case-Control Study

Objective:To compare the outcomes of a strategy of surveillance versus surgical resection in patients with esophageal cancer (EC) experiencing complete clinical response (cCR) after chemoradiation (CRT). Background:In EC, it remains unclear whether a strategy of surveillance or esophagectomy is appropriate after cCR to CRT. Methods:From 1995 to 2009, 222 operable patients had a cCR based on the results of a computed tomographic scan, endoscopy with biopsies and, when performed, a positron emission tomographic scan. Through an intention-to-treat case-control study, 59 patients treated with CRT and surveillance (group Surv) were matched 1:2 with 118 patients treated by CRT followed by surgery (group Surg), according to age, gender, tumor location and stage, histology, American Society of Anesthesiologists score, and nutritional status. Results:The 2 groups were comparable according to the matched variables (P > 0.276). In group Surg, the postoperative mortality rate was 4.2% with evidence of residual tumor in 34.6% of specimens. In group Surv, 2 salvage esophagectomies were performed. Despite the higher dose of radiotherapy received in group Surv (50 vs 45 Gys, P = 0.003), median survival was lower (31 vs 83 months, P = 0.001), with disease recurrence that was more frequent (50.8% vs 32.7%, P = 0.021), occurred earlier (7.8 vs 19.0 months, P = 0.002) and more often locoregional (46.7% vs 16.2%, P = 0.007) in nature. Surgical resection was independently associated with less recurrence [odds ratio = 0.4, 95% confidence interval (CI): 0.2–0.8, P = 0.006] and better survival (hazard ratio = 0.5, 95% CI: 0.3–0.8, P = 0.006). Conclusions:Survival of EC patients with a cCR after CRT is better after surgery compared to simply surveillance. In patients of low operative risk and operable disease, surgery should be considered to improve control of locoregional disease and to overcome the inherent limitations of clinical response assessment.
Impact of polyunsaturated fatty acids on oxidized low density lipoprotein-induced U937 cell apoptosis.

AIM Dietary supplements in polyunsaturated fatty acids (PUFA), particularly omega-3, are well known for their beneficial effects in preventing cardiovascular diseases (CVD). The aim of this study was to determine the role of PUFA on the modulation of apoptosis induced by hypochlorous acidoxidized LDL (HOCl-oxLDL) in U937 cells. METHODS We tested the effect of monocyte cell line U937 supplementation with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (ARA) or oleic acid (OA) on the modulation of HOCl-oxLDL-induced apoptosis. RESULTS First, we showed the incorporation of fatty acids in the cellular membrane in U937 cells. Then, we showed that both EPA and ARA exerted a pro-apoptotic effect through the intrinsic mitochondrial apoptotic pathway including the dissipation of mitochondrial membrane potential followed by cardiolipin depletion, the downstream activation of caspase-3 and the increase in DNA fragmentation. The pro-apoptotic effect of EPA or ARA was completely blocked in U937/Bcl-2 cells. CONCLUSIONS A new mechanism of dietary supplements in PUFA with likely consequences in apoptosis could be suggested through the mitochondrial pathway in monocytes.
Multiple Consecutive Lavage Samplings Reveal Greater Burden of Disease and Provide Direct Access to the Nontypeable Haemophilus influenzae Biofilm in Experimental Otitis Media

ABSTRACT The typically recovered quantity of nontypeable Haemophilus influenzae (NTHi) bacteria in an ex vivo middle ear (ME) aspirate from the chinchilla model of experimental otitis media is insufficient for direct analysis of gene expression by microarray or of lipopolysaccharide glycoforms by mass spectrometry. This prompted us to investigate a strategy of multiple consecutive lavage samplings to increase ex vivo bacterial recovery. As multiple consecutive lavage samples significantly increased the total number of bacterial CFU collected during nasopharyngeal colonization or ME infection, this led us to evaluate whether bacteria sequentially acquired from consecutive lavages were similar. Comparative observation of complete ex vivo sample series by microscopy initially revealed ME inflammatory fluid consisting solely of planktonic-phase NTHi. In contrast, subsequent lavage samplings of the same infected ear revealed the existence of bacteria in two additional growth states, filamentous and biofilm encased. Gene expression analysis of such ex vivo samples was in accord with different bacterial growth phases in sequential lavage specimens. The existence of morphologically distinct NTHi subpopulations with varying levels of gene expression indicates that the pooling of specimens requires caution until methods for their separation are developed. This study based on multiple consecutive lavages is consistent with prior reports that NTHi forms a biofilm in vivo, describes the means to directly acquire ex vivo biofilm samples without sacrificing the animal, and has broad applicability for a study of mucosal infections. Moreover, this approach revealed that the actual burden of bacteria in experimental otitis media is significantly greater than was previously reported. Such findings may have direct implications for antibiotic treatment and vaccine development against NTHi.
GOTHiC, a probabilistic model to resolve complex biases and to identify real interactions in Hi-C data

Hi-C is one of the main methods for investigating spatial co-localisation of DNA in the nucleus. However, the raw sequencing data obtained from Hi-C experiments suffer from large biases and spurious contacts, making it difficult to identify true interactions. Existing methods use complex models to account for biases and do not provide a significance threshold for detecting interactions. Here we introduce a simple binomial probabilistic model that resolves complex biases and distinguishes between true and false interactions. The model corrects biases of known and unknown origin and yields a p-value for each interaction, providing a reliable threshold based on significance. We demonstrate this experimentally by testing the method against a random ligation dataset. Our method outperforms previous methods and provides a statistical framework for further data analysis, such as comparisons of Hi-C interactions between different conditions. GOTHiC is available as a BioConductor package (http://www.bioconductor.org/packages/release/bioc/html/GOTHiC.html).
A systemic-transactional conceptualization of stress and coping in couples

Until recently, research on stress and coping has primarily focused on the individual, where we find a large body of theoretical and empirical work. On the other hand, there are far fewer empirical, and nearly no theoretical, approaches to these phenomena in couples. Stress in couples and forms of dyadic coping in a systemic view have largely been neglected as topics and have not yet attracted the attention of many psychologists. Although some models exist for family stress and family coping in regard to critical life events and transitions and thus may be applied in the context of dyadic intimate relationships as well, most of these approaches have several weaknesses: (1) Their utility concerning every day stress and daily hassles is limited. (2) Furthermore, stress and coping are seldom discussed as a systemic phenomenon, but rather as individual affairs. (3) Theoretical conceptualizations are generally rare. In this article, I will try to clarify stress and coping from a systemic and transactional point of view by proposing a new model of stress and coping processes in intimate relationships. In addition to a discussion of different forms of stress in couples, we will present a taxonomy of different coping forms: common dyadic coping, supportive dyadic coping and delegated dyadic coping. Moreover, factors determining whether dyadic coping is practiced or not will be outlined.
Tracking TCRβ Sequence Clonotype Expansions during Antiviral Therapy Using High-Throughput Sequencing of the Hypervariable Region

To maintain a persistent infection viruses such as hepatitis C virus (HCV) employ a range of mechanisms that subvert protective T cell responses. The suppression of antigen-specific T cell responses by HCV hinders efforts to profile T cell responses during chronic infection and antiviral therapy. Conventional methods of detecting antigen-specific T cells utilize either antigen stimulation (e.g., ELISpot, proliferation assays, cytokine production) or antigen-loaded tetramer staining. This limits the ability to profile T cell responses during chronic infection due to suppressed effector function and the requirement for prior knowledge of antigenic viral peptide sequences. Recently, high-throughput sequencing (HTS) technologies have been developed for the analysis of T cell repertoires. In the present study, we have assessed the feasibility of HTS of the TCRβ complementarity determining region (CDR)3 to track T cell expansions in an antigen-independent manner. Using sequential blood samples from HCV-infected individuals undergoing antiviral therapy, we were able to measure the population frequencies of >35,000 TCRβ sequence clonotypes in each individual over the course of 12 weeks. TRBV/TRBJ gene segment usage varied markedly between individuals but remained relatively constant within individuals across the course of therapy. Despite this stable TRBV/TRBJ gene segment usage, a number of TCRβ sequence clonotypes showed dramatic changes in read frequency. These changes could not be linked to therapy outcomes in the present study; however, the TCRβ CDR3 sequences with the largest fold changes did include sequences with identical TRBV/TRBJ gene segment usage and high junction region homology to previously published CDR3 sequences from HCV-specific T cells targeting the HLA-B*0801-restricted 1395HSKKKCDEL1403 and HLA-A*0101-restricted 1435ATDALMTGY1443 epitopes. The pipeline developed in this proof of concept study provides a platform for the design of future experiments to accurately address the question of whether T cell responses contribute to SVR upon antiviral therapy. This pipeline represents a novel technique to analyze T cell dynamics in situations where conventional antigen-dependent methods are limited due to suppression of T cell functions and highly diverse antigenic sequences.
Causes and consequences of nuclear gene positioning

ABSTRACT The eukaryotic genome is organized in a manner that allows folding of the genetic material in the confined space of the cell nucleus, while at the same time enabling its physiological function. A major principle of spatial genome organization is the non-random position of genomic loci relative to other loci and to nuclear bodies. The mechanisms that determine the spatial position of a locus, and how position affects function, are just beginning to be characterized. Initial results suggest that there are multiple, gene-specific mechanisms and the involvement of a wide range of cellular machineries. In this Commentary, we review recent findings from candidate approaches and unbiased screening methods that provide initial insight into the cellular mechanisms of positioning and their functional consequences. We highlight several specific mechanisms, including tethering of genome regions to the nuclear periphery, passage through S-phase and histone modifications, that contribute to gene positioning in yeast, plants and mammals. Summary: A review of the ways different organisms utilize multiple mechanisms to position genes in the 3D space of their nucleus, and how this, in turn, can affect their activity and function.
Bioassay‐guided isolation of an anti‐ulcer diterpenoid from Croton reflexifolius: role of nitric oxide, prostaglandins and sulfhydryls

Croton reflexifolius H. B. K (Euphorbiaceae) is a very common medicinal plant in the Huastecan region of Mexico that, according to local folk medicine, is considered useful in the treatment of gastritis and gastric ulcer. We have aimed to test the validity of this practice by using the experimental model of an ethanol‐induced gastric ulcer in male Wistar rats. The results showed that C. reflexifolius had gastroprotector activity, that the hexane extract had the highest protective activity (64.38 ± 7.72%), and that polyalthic acid isolated from this extract was the main active gastroprotector agent. Rats treated orally with polyalthic acid showed a gastroprotective effect similar to that elicited by carbenoxolone. As with carbenoxolone, the effect elicited by polyalthic acid was attenuated by pretreatment with either NG‐nitro‐l‐arginine methyl ester (70 mgkg−1, i.p.), a nitric oxide (NO) synthase inhibitor, or N‐ethylmaleimide (10 mgkg−1, s.c.), a blocker of sulfhydryl groups. This suggested that the gastroprotective mechanism of this diterpenoid involved the participation of both NO and endogenous sulfhydryl groups. Contrary to carbenoxolone, the gastroprotective effect of polyalthic acid was not affected by the inhibition of prostaglandin synthesis with indometacin (10 mgkg−1, s. c.). In conclusion, Croton reflexifolius contains compounds with gastroprotector activity. Polyalthic acid, which was isolated from this plant, was the main compound with gastroprotector activity, having effectiveness similar to that found with the use of carbenoxolone. Whereas NO and sulfhydryl groups were involved in the mechanisms of gastroprotective action of polyalthic acid, prostaglandins were not.