Miracle-dz/UniFAR-FTUs huggingface dataset:
Susceptibility of enterohaemorrhagic Escherichia coli to azithromycin in France and analysis of resistance mechanisms.

OBJECTIVES Antibiotic therapy is not recommended during enterohaemorrhagic Escherichia coli (EHEC) infection. However, the potential benefit of azithromycin has recently been described. This study was conducted to evaluate the macrolide susceptibility of EHEC isolates from France and to analyse the mechanisms of resistance to azithromycin in EHEC. METHODS Strains from patients with EHEC infections were collected by the associated French National Reference Laboratory for E. coli from 2004 to 2014. Antimicrobial susceptibility testing was performed by disc diffusion and Etest methods. For strains presenting macrolide resistance, antibiotic resistance genes were searched for by PCR. Genetic transfer was performed by conjugation and plasmid analysis was done by Southern-blot hybridization after PFGE. RESULTS We tested 508 isolates of EHEC. Azithromycin MICs ranged between 0.25 and 16 mg/L (median = 3 mg/L), except for two atypical strains, 34396 and 36493, for which MICs were >256 mg/L. Plasmid transferability of macrolide resistance was demonstrated. Strain 34396, of serotype O106:H18, harboured two macrolide resistance genes [mph(A) and erm(B)] and two other antimicrobial resistance genes (blaDHA-1 for β-lactam resistance and qnrB4 for quinolone resistance). mph(A), blaDHA-1 and qnrB4 were localized on the same plasmid. Strain 36493 belonging to the highly virulent O26:H11 EHEC clonal group harboured a plasmid containing mph(A). CONCLUSIONS For the first time we describe plasmid-borne macrolide resistance genes in EHEC strains. Dissemination of such plasmids may threaten the potential benefit of azithromycin during the management of patients infected or colonized with EHEC. Determination of azithromycin MICs should be considered prior to its therapeutic use and 16 mg/L may be used as the epidemiological cut-off value.
Next steps in cardiovascular disease genomic research--sequencing, epigenetics, and transcriptomics.

BACKGROUND Genomic research in cardiovascular disease (CVD) has progressed rapidly over the last 5 years. In most cases, however, these groundbreaking observations have not yet been accompanied by clinically applicable tools for risk prediction, diagnosis, or therapeutic interventions. CONTENT We reviewed the scientific literature published in English for novel methods and promising genomic targets that would permit large-scale screening and follow-up of recent genomic findings for CVD. We anticipate that advances in 3 key areas will be critical for the success of these projects. First, exome-centered and whole-genome next-generation sequencing will identify rare and novel genetic variants associated with CVD and its risk factors. Improvements in methods will also greatly advance the field of epigenetics and gene expression in humans. Second, research is increasingly acknowledging that static DNA sequence variation explains only a fraction of the inherited phenotype. Therefore, we expect that multiple epigenetic and gene expression signatures will be related to CVD in experimental and clinical settings. Leveraging existing large-scale consortia and clinical biobanks in combination with electronic health records holds promise for integrating epidemiological and clinical genomics data. Finally, a systems biology approach will be needed to integrate the accumulated multidimensional data. SUMMARY Novel methods in sequencing, epigenetics, and transcriptomics, plus unprecedented large-scale cooperative efforts, promise to generate insights into the complexity of CVD. The rapid accumulation and integration of knowledge will shed light on a considerable proportion of the missing heritability for CVD.
Genetics of Parkinson's disease

A genetic contribution to the etiology of Parkinson's disease (PD) is now well established, based on the demonstration of a familial aggregation of the disease as demonstrated by several case–control and twin studies, and on the description of large multigenerational families, in whom PD is inherited in a Mendelian fashion. In a few families with autosomal dominant inheritance and typical Lewy‐body pathology, a gene locus has been mapped to the long arm of chromosome 4, and mutations have been identified in the gene for α‐synuclein. A gene causing autosomal recessive parkinsonism of juvenile onset has been mapped to chromosome 6, and the causative gene has been identified and named Parkin. This form of parkinsonism differs pathologically from the sporadic disease, as no Lewy bodies are found in the substantia nigra. A third locus, again in families with dominant inheritance, typical Lewy‐body pathology and late onset, has been mapped to chromosome 2p13. At present, there is no evidence that any of these genes for familial Parkinsonian syndromes have a direct role in the etiology of the common sporadic form of PD. However, the elucidation of the molecular sequence of events leading to nigral degeneration in these inherited cases is likely to shed light on the molecular pathogenesis of this common neurodegenerative disorder.
Germination of Spores of Bacillus Species: What We Know and Do Not Know

ABSTRACT Spores of Bacillus species can remain in their dormant and resistant states for years, but exposure to agents such as specific nutrients can cause spores' return to life within minutes in the process of germination. This process requires a number of spore-specific proteins, most of which are in or associated with the inner spore membrane (IM). These proteins include the (i) germinant receptors (GRs) that respond to nutrient germinants, (ii) GerD protein, which is essential for GR-dependent germination, (iii) SpoVA proteins that form a channel in spores' IM through which the spore core's huge depot of dipicolinic acid is released during germination, and (iv) cortex-lytic enzymes (CLEs) that degrade the large peptidoglycan cortex layer, allowing the spore core to take up much water and swell, thus completing spore germination. While much has been learned about nutrient germination, major questions remain unanswered, including the following. (i) How do nutrient germinants penetrate through spores' outer layers to access GRs in the IM? (ii) What happens during the highly variable and often long lag period between the exposure of spores to nutrient germinants and the commitment of spores to germinate? (iii) What do GRs and GerD do, and how do these proteins interact? (iv) What is the structure of the SpoVA channel in spores' IM, and how is this channel gated? (v) What is the precise state of the spore IM, which has a number of novel properties even though its lipid composition is very similar to that of growing cells? (vi) How is CLE activity regulated such that these enzymes act only when germination has been initiated? (vii) And finally, how does the germination of spores of clostridia compare with that of spores of bacilli?
EXAMINATION OF THE WEB PEDAGOGICAL CONTENT KNOWLEDGE OF PRE-SERVICE TEACHERS IN TERMS OF SOME VARIABLES

In this study, it is aimed to investigate web pedagogical knowledge and the internet habits of pre-service teachers. Survey method is used in this study. Study group of this research consists of 343 pre-service teachers. 221 pre-service teachers of which are attending the last year at the departments of science, primary school, social science and 112 of which are receiving pedagogical formation at the Faculty of Education at Adnan Menderes University. Following the searches, there are significant differences in favor of seniors, having computer, often usage of internet and social networks. As a result, pre-service teachers' effective use of ICT in educational environments should be increased. The number of unit contents with more activities and model applications of information technologies should be increased in the curriculum.
Prognostic value of CD44 variant exon 6 expression in non-small cell lung cancer: a meta-analysis.

BACKGROUND CD44v6 (CD44 variant exon 6) is the chief CD44 variant isoform regulating tumor invasion, progression, and metastasis. The prognostic value of CD44v6 expression in non small cell lung cancer (NSCLC) has been evaluated in many studies, but the results have remained controversial. Thus, we performed a meta- analysis of currently available studies to investigate the prognostic value of CD44v6 expression in NSCLC patients and the relationship between the expression of CD44v6 and clinicopathological features. MATERIALS AND METHODS Two independent reviewers searched the relevant literature in Pubmed, Medline and Embase from 1946 to January 2014. Overall survival (OS) and various clinicopathological features were collected from included studies. This meta-analysis was accomplished using STATA 12.0 and Revman 5.2 software. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated to estimate the effects. RESULTS A total of 921 NSCLC patients from ten studies met the inclusion criteria. The results showed that CD44v6 high expression was a prognostic factor for poor survival (HR=1.91, 95%CI=1.12-3.26, p<0.05). With respect to clinicopathological features, CD44v6 high expression was related to histopathologic type (squamous cell carcinoma versus adenocarcinoma: OR=2.72, 95%CI=1.38-5.38, p=0.004), and lymph node metastasis (OR=3.02, 95%CI=1.93-4.72, p<0.00001). CONCLUSIONS Our results suggested CD44v6 high expression as a poor prognostic factor for NSCLC, and CD44v6 expression is associated with lymph node metastasis and histopathologic type. Therefore, CD44v6 expression can be used as a novel prognostic marker in NSCLC cases.
Autonomic nervous system and sudden cardiac death. Experimental basis and clinical observations for post-myocardial infarction risk stratification.

The analysis of the autonomic control of the heart, by means of indirect markers, may represent a new approach for identifying patients at higher risk for sudden cardiac death after a myocardial infarction. This possibility is based on the evidence that autonomic responses during acute myocardial ischemia are a major determinant of the outcome (i.e., occurrence of ventricular fibrillation or survival). Specifically, sympathetic activation can trigger malignant arrhythmias, whereas vagal activity may exert a protective effect. Several experimental observations have provided new insights on the relation between sympatho-vagal interactions and the likelihood for the occurrence of ventricular fibrillation. In an established experimental model for sudden death involving conscious dogs with a healed myocardial infarction, either depressed reflex chronotropic responses during a blood pressure rise or reduced variability of heart rate (respectively, markers of reflex and tonic cardiac vagal activity) identify dogs at greater risk to develop malignant arrhythmias during a new ischemic episode. In anesthetized cats, direct neural recording of vagal activity to the heart confirmed that vigorous reflex vagal activation during acute myocardial ischemia is associated with protection from ventricular fibrillation. Furthermore, in these experiments the reflex neural response to acute myocardial ischemia was predicted by the analysis of baroreflex sensitivity. The antifibrillatory effect of vagal activation is confirmed by the prevention of ventricular fibrillation during acute ischemia in dogs susceptible to sudden cardiac death by direct electrical stimulation of the right vagus. The clinical counterpart of these experimental data lies in three separate prospective studies showing a higher cardiac mortality in patients who after a myocardial infarction have a depressed baroreflex sensitivity or a decreased heart rate variability. A definitive answer on the role that the analysis of markers of cardiac vagal activity may play in risk stratification of patients with coronary artery disease should be provided by Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI), an ongoing prospective study. In ATRAMI, baroreflex sensitivity and heart rate variability will be assessed within 20 days after a myocardial infarction in 1,200 patients enrolled in Europe, U.S.A. , and Japan with a minimum follow up of one year.
Multifractal feature descriptor for diagnosing liver and prostate cancers in H&E stained histologic images

Histologic imaging plays an important role in discriminating cancerous tissues of several body organs. However, the human histopathological examinations may be subjective and error prone, because of the complexity of the appearances of the histologic texture. These limitations can be overcome by adopting quantitative computational methods with human histopathological examination routines. This study proposes a new feature descriptor to characterize texture of histologic images. The proposed method derives a discriminative feature space by observing the self-similarity characteristics of the texture based on fractal geometry. The merit of utilizing fractal geometry to describe the histologic texture is assessed by a classification experiment. The experimental results indicate that the proposed feature descriptor can classify cancer and non-cancer tissues of histologic images of liver and prostate images around 95% of correct classification rate.
A unified perspective of RTN and BTI

It has recently been suggested that random telegraph noise (RTN) and the bias temperature instability (BTI) are due to similar defects. Here we thoroughly analyze this hypothesis using nano-scale devices to show that (i) all defects that contribute to BTI recovery can also become spontaneously charged to produce an RTN event, (ii) most RTN defects also contribute to BTI recovery, (iii) the distribution of step-heights, capture and emission times is equally wide and similar for RTN and BTI, and (iv) both RTN and BTI defects are volatile, meaning that they can disappear and reappear. From these observations we conclude that RTN and the recoverable component of BTI are very likely due to the same defects. As a very important consequence, RTN and BTI must be analyzed and guardbanded against together. In particular, since conventional RTN analysis dominantly captures defects with the strongest contribution to the noise power, it misses the defects with large capture times. As we will show, however, it is exactly these defects with large capture times that may by chance become occupied at the same time after long times, thereby leading to very large NBTI-like threshold voltage fluctuations in an RTN setting. Conversely, conventional BTI analysis based on the expectation value of the stochastic trap behavior misses these RTN-like fluctuations when extrapolated down to operating voltages, potentially leading to wrong conclusions.
Assessing Residents’ Competencies at Baseline: Identifying the Gaps

Purpose. Entering residents have variable medical school experiences and differing knowledge and skill levels. To structure curricula, enhance patient safety, and begin to meet accreditation requirements, baseline assessment of individual resident's knowledge and skills is needed. To this end, in 2001 the University of Michigan Health System created the Postgraduate Orientation Assessment (POA), an eight-station, objective structured clinical examination for incoming residents. Method. The POA, administered at orientation, included items addressing critical laboratory values, cross-cultural communication, evidence-based medicine, radiographic image interpretation, informed consent, pain assessment and management, aseptic technique, and system compliance such as fire safety. The POA assessed many of the skills needed by interns in their initial months of training when supervision by senior physicians might not be present. Results. In 2002, 132 interns from 14 different specialties and 59 different schools participated in the POA. The mean score was 74.8% (SD = 5.8). When scores were controlled for U.S. Medical Licensing Examination scores, there were no significant differences in performance across specialties. There were differences between University of Michigan Medical School graduates and those from other institutions (p < .001). Eighty-one percent of the residents would recommend the POA. Conclusions. The POA provides a feasible format to measure initial knowledge and skills and identify learning needs. Orientation is an effective time to identify important gaps in learning between medical school and residency. This is the first step in a continuing evaluation of the Accreditation Council for Graduate Medical Education's general competencies.
Effects of a Prethickened Formula on Esophageal pH and Gastric Emptying of Infants With GER

Objective(s) Advantages of prethickened formulas (AR) with regards to esophageal pH and gastric emptying were investigated in this study as compared with a regular formula (R). Study Design Seventy-four healthy infants, <6 months old, with gastroesophageal reflux were enrolled into the study. All infants underwent 24-hour esophageal pH monitoring while receiving R and AR, alternately. Electrogastrography was measured before and after feeding each study formula. Thereafter, the infants were randomly assigned to receive either R or AR for 1 month. Episodes of regurgitation, vomiting, coughing, crying, and bowel movements were recorded on a weekly interval. Results Reflux index (RI) of AR-fed infants were lower (5.64%) than the R-fed infants (7.77%) showing a significant difference (P<0.01) between the 2 groups, favoring AR. Eighty-seven percent of infants improved their RI while receiving the AR formula. Electrogastrography variables were not significantly different between the 2 study groups. A significant decrease (P<0.01) in the daily episodes of regurgitation and vomiting was observed in the AR-fed infants. No adverse events were reported during the study. Conclusions Prethickened infant formula was effective in reducing clinical symptoms of uncomplicated gastroesophageal reflux and reducing RI. Prethickened formulas do not alter gastric emptying time and was very well tolerated.
Towards the time varying estimation of complex brain connectivity networks by means of a General Linear Kalman Filter approach

One of the main limitations of the brain functional connectivity estimation methods based on Autoregressive Modeling, like the Granger Causality family of estimators, is the hypothesis that only stationary signals can be included in the estimation process. This hypothesis precludes the analysis of transients which often contain important information about the neural processes of interest. On the other hand, previous techniques developed for overcoming this limitation are affected by problems linked to the dimension of the multivariate autoregressive model (MVAR), which prevents from analysing complex networks like those at the basis of most cognitive functions in the brain. The General Linear Kalman Filter (GLKF) approach to the estimation of adaptive MVARs was recently introduced to deal with a high number of time series (up to 60) in a full multivariate analysis. In this work we evaluated the performances of this new method in terms of estimation quality and adaptation speed, by means of a simulation study in which specific factors of interest were systematically varied in the signal generation to investigate their effect on the method performances. The method was then applied to high density EEG data related to an imaginative task. The results confirmed the possibility to use this approach to study complex connectivity networks in a full multivariate and adaptive fashion, thus opening the way to an effective estimation of complex brain connectivity networks.
A fast and power efficient architecture to parallelize LSTM based RNN for cognitive intelligence applications

Long Short-Term Memory (LSTM) based Recurrent Neural Networks (RNNs) are promising for cognitive intelligence applications like speech recognition, image caption and nature language processing, etc. However, the cascade dependent structure in RNN with huge amount of power inefficient operations like multiplication, memory accessing and nonlinear transformation, could not guarantee high computing speed and low power consumption. In this work, by exploiting semantic correlation, we propose a semantic correlation based data pre-fetch method to break the dependency and achieve parallel processing. Based on this method, a full parallel and pipeline architecture that tackles huge amount operations is designed. Experiments on benchmarks of image caption, speech recognition and language processing show that, this work improves computing speed by 5.1 times, 44.9 times and 1.53 times, respectively, and power efficiency by 1885.7 times, 4061.5 times and 127.5 times, respectively, when compared with state-of-the-art works.
Cigarette smoking and the risk of diabetes in women.

OBJECTIVES Noninsulin-dependent diabetes mellitus, a major risk factor for cardiovascular disease, is prevalent in more than 12 million Americans. A voluminous amount of data demonstrates that cigarette smoking is an important cause of cancer and coronary heart disease. However, the association between cigarette smoking and the risk of diabetes is virtually unexplored, especially in women. METHODS We examined the association between smoking and the incidence of noninsulin-dependent diabetes mellitus among 114,247 female nurses who were free of diabetes, cardiovascular disease, and cancer in 1976. We collected exposure information and disease status prospectively for 12 years from biennially self-administered questionnaires. RESULTS Current smokers had an increased risk of diabetes, and we observed a significant dose-response trend for higher risk among heavier smokers. During 1,277,589 person-years of follow-up, 2333 women were clinically diagnosed with diabetes. The relative risk of diabetes, adjusted for obesity and other risk factors, was 1.42 among women who smoked 25 or more cigarettes per day compared with nonsmokers. CONCLUSIONS These data suggest that cigarette smoking may be an independent, modifiable risk factor for noninsulin-dependent diabetes mellitus.
Design patterns in object oriented analysis and design

Design pattern is a general reusable solution to a commonly occurring problem in software development. Good OO designs are reusable, extensible and maintainable. Patterns only give you a general rule not code. Patterns show you how to build systems with good OO design qualities. Most of them address issues of change in software and allow some part of a system to vary independently of all other parts by trying to take what varies in a system and encapsulate it. Patterns also provide a shared language that can maximize the value of your communication with other developers. In this paper, we briefly introduce the concept of software design pattern and give a research on some design patterns including Strategy Pattern, Iterator Pattern, Adapter Pattern and Façade Pattern.