Miracle-dz/UniFAR-FTUs huggingface dataset:
Differences in atrial fibrillation management strategies among physicians: A survey based study

Aim: Previous data reflected confusions about classification and management of atrial fibrillation (AF) among physicians. Although relatively clear suggestions of dedicated guidelines, poor adaptation of them to routine clinical practice may result with suboptimal prevention and treatment measures. As a main stakeholder of management, physicians' perceptions about the disease have major role. The study aimed to assess confusions and concordances of physicians about the definition and management of the disease. Methods and Results: We developed a web-based survey about AF consisting of 27 questions regarding valvular or non-valvular AF perception, using thromboembolic and bleeding risk scores, antithrombotic management and rate/rhythm control strategies. Two hundred and thirty two physicians participated and 224(97%) of them completed the survey. Although only cardiologists were invited to the survey, 27 physicians from different specialties also responded the survey. Half of the physicians reported that ≥40% of their patients had valvular AF. Dramatically, the survey responses revealed that nearly one-third of physicians classified the AF patients with mitral regurgitation as valvular AF. Most of the physicians denoted that they were using bleeding and stroke risk scores before deciding oral anticoagulation therapy and also preferring long term rhythm-control strategy in AF patients with systolic heart failure. However, results exposed evident disparities among physicians at specific aspects of the disease management. Conclusion: The survey-based study demonstrated a great heterogeneity in classification and management of AF among physicians because of guideline confusions/failures, inadequate evidence about some specific conditions and not being able to dominate the guidelines by physicians.
Comparison of Pathvysion and Poseidon HER2 FISH assays in measuring HER2 amplification in breast cancer: a validation study

Aims The current study was done as a validation study prior to setting up a clinical HER2 testing service using the new commercial Poseidon HER2 fluorescence in situ hybridisation (FISH) assay. However, it was felt that the experience of the authors of this study may be of interest to other laboratories when considering setting up a HER2 diagnostic facility. Methods 122 patients who had been diagnosed with invasive breast cancer were selected. Immunolabelling with HercepTest, PathVysion and Poseidon FISH assays were carried out using tissue microarray blocks. Results Concordance correlation coefficients showed near perfect agreement in average HER2 and centromere specific signal counts per cell and in the HER2/CEP17 ratios between the PathVysion and the Poseidon FISH assays. In addition, the κ measure showed perfect agreement (κ 0.9441, p<0.0001), and if only 2+ cases were considered there was substantial agreement (κ 0.7671, p=0.0006), between the two assays. The sensitivity and the specificity of the Poseidon FISH kit were calculated to be 95.2% and 100%, respectively, whereas the positive predictive value (PPV) and negative predictive value (NPV) were 100% and 99%, respectively. With regard to the ability to presume HER2 polysomy, the Poseidon FISH kit had a sensitivity of 93.3% and a specificity of 99.1%, with PPV and NPV of 93.3% and 99.1%, respectively, as assessed with PathVysion classification as the reference. Conclusions Statistical analysis confirmed that the two FISH assays are comparable in terms of detection of HER2 gene amplification. Proceeding from these findings, the genetic diagnoses obtained with the Poseidon kit can be considered to be as valuable as the results from the Food and Drug Administration approved PathVysion assay, and its utilisation in routine HER2 diagnostics is proposed.
Graph Homomorphisms, Circular Colouring, and Fractional Covering by H-cuts

A graph homomorphism is a vertex map which carries edges from a source graph to edges in a target graph. The instances of the Weighted Maximum H-Colourable Subgraph problem (MAX H-COL) are edge-weighted graphs G and the objective is to find a subgraph of G that has maximal total edge weight, under the condition that the subgraph has a homomorphism to H; note that for H=K_k this problem is equivalent to MAX k-CUT. Farnqvist et al. have introduced a parameter on the space of graphs that allows close study of the approximability properties of MAX H-COL. Specifically, it can be used to extend previously known (in)approximability results to larger classes of graphs. Here, we investigate the properties of this parameter on circular complete graphs K_{p/q}, where 2 <= p/q <= 3. The results are extended to K_4-minor-free graphs and graphs with bounded maximum average degree. We also consider connections with Samal's work on fractional covering by cuts: we address, and decide, two conjectures concerning cubical chromatic numbers.
Association between DNA Methylation in the miR-328 5’-Flanking Region and Inter-individual Differences in miR-328 and BCRP Expression in Human Placenta

MicroRNA (miRNA) are non-coding small RNA that regulate gene expression. MiR-328 is reported to influence breast cancer resistance protein (BCRP) expression in cancer cells. As a large inter-individual difference in BCRP levels is observed in various human tissues, the contribution of miR-328 to these differences is of interest. We hypothesized that DNA methylation in the miR-328 promoter region is responsible for the difference in miR-328 levels, leading to inter-individual variability in BCRP levels in human placenta. The association between placental miR-328 and BCRP levels was analyzed, and then DNA methylation in the miR-328 5'-flanking region and regulatory mechanisms causing inter-individual differences in miR-328 and BCRP levels were examined. MiR-328 expression was significantly correlated with BCRP mRNA (Rs = -0.560, P < 0.01) and protein (Rs = -0.730, P < 0.01) levels. It was also up-regulated by the demethylating agent 5-aza-2’-deoxycytidine in BCRP-expressing cells. Luciferase assays with differentially methylated reporter constructs indicated that methylation in the miR-328 5’-flanking region including a predicted CpG island remarkably decreased transcriptional activity compared to that in unmethylated constructs. We selected CCAAT/enhancer binding protein α (C/EBPα), located within the predicted CpG island, by in silico analysis. To elucidate the role of C/EBPα in miR-328 expression, a chromatin immunoprecipitation assay, promoter deletion analysis, and electrophoretic mobility shift assay (EMSA) were performed. C/EBPα-binding site-truncated constructs showed significantly decreased promoter activity, and EMSA indicated that the C/EBPα-binding sites were located in the CpG island. Finally, the methylation patterns of several CpG dinucleotides proximal to two C/EBPα-binding sites in the miR-328 5’-flanking region were correlated negatively with miR-328 levels, and positively with BCRP levels in human placental samples. These results suggest that methylation patterns in the miR-328 5’-flanking region are involved in the inter-individual difference in BCRP levels in human placenta.
Testing gene function early in the B cell lineage in mb1-cre mice

The mb1 gene encodes the Ig-α signaling subunit of the B cell antigen receptor and is expressed exclusively in B cells beginning at the very early pro-B cell stage in the bone marrow. We examine here the efficacy of the mb1 gene as a host locus for cre recombinase expression in B cells. We show that by integrating a humanized cre recombinase into the mb1 locus we obtain extraordinarily efficient recombination of loxP sites in the B cell lineage. The results from a variety of reporter genes including the splicing factor SRp20 and the DNA methylase Dnmt1 suggest that mb1-cre is probably the best model so far described for pan-B cell-specific cre expression. The availability of a mouse line with efficient cre-mediated recombination at an early developmental stage in the B lineage provides an opportunity to study the role of various genes specifically in B cell development and function.
A Petri Net-Based Model for Aspect-Oriented Web Service Composition

Aspect-Oriented Programming is an emerging programming paradigm. Now the concept of aspect-orientation stretches over other development phases and other domains. Many researches have focused on aspect-oriented web service composition domain. However, none of them offers a formal foundation for the aspect-oriented service composition. In this paper, we propose a Petri net-based algebra for aspect-oriented web service composition. In our model, web service composition is modeled as basic composition net and aspect nets, and then weaving mechanism is provided to compose the basic net and aspect nets. The formal semantics of the composition operation is expressed in terms of Petri nets. Thus, the properties of woven composite service can be verified and analyzed based on the underlying Petri net. Keywords-Web service composition; Aspect-Oriented; Petri Net
Effect of Timing of Silicone Tube Removal on the Result of Duct Intubation in Children With Congenital Nasolacrimal Duct Obstruction

Purpose: To evaluate the results and complications of primary silicone tube intubation of children presenting with congenital nasolacrimal duct obstruction in relation to the timing of tube removal. Methods: This hospital-based retrospective observational case series reviewed the records of 236 primary nasolacrimal duct intubations performed during the last 10 years regarding age at operation, procedure details, timing of tubal removal, and complications. The main outcome measure was success rate in relation to duration of silicone intubation. Results: The overall success rate was 82.2%. The reoperation rate was higher in all cases of inadvertent early silicone tube removal before 6 weeks (p = 0.002). There was no difference in the success rate between cases of tube removal before or after 6 weeks in children younger than 24 months of age, whereas older children showed a higher reoperation rate if the tubes were removed prior to 6 weeks (p = 0.003). Conclusions: Removal of the silicone tube at 6 weeks is less likely to affect the final result in children younger than 2 years of age. Removal of the tube after at least 3 months is recommended for older children.
Eriksholm Workshop on Hearing Impairment and Cognitive Energy.

article describes a pilot study evaluating the effects of hearing loss and auditory task difficulty on subjective and physiological measures of effort/stress including pupillometry and two endocrine stress biomarkers: cortisol and chromogranin A. The three physiological indicators of cognitive load or stress (PPD, cortisol, and CgA) are not equally affected by speech testing or hearing impairment. provides a review of the neurophysiological changes that take place in the aging ear–brain system and that are believed to affect the listening abilities of older adults. Also described is how audiologic rehabilitation, including hearing aid amplification and listening training, is used to reduce the amount of cognitive resources required for effective auditory communication.
Stability of small non-coding RNA reference gene expression in the rat retina during exposure to cyclic hyperoxia

Purpose Oxygen-induced retinopathy (OIR) is a robust animal model of human retinopathy of prematurity that readily allows changes in retinal gene and microRNA (miRNA) expression in response to fluctuations in oxygen levels to be studied. We sought to identify small non-coding RNA (ncRNA) genes that showed stable expression upon exposure to varying levels of oxygen, with different developmental stages and in different rat strains, to act as reference genes for normalizing miRNA expression in a rat model of OIR. Methods Expression of five small ncRNAs (U6 snRNA, miR-16, U87, 4.5S RNA (H) “Variant 1”, and 5S ribosomal RNA [rRNA]) were tested on a standard RNA pool and representative retinal samples from P5, P6, P9, and P14 from room air– and cyclic hyperoxia–exposed rats using reverse transcription (RT)-qPCR, to assess the effect of developmental stage and exposure to fluctuations in oxygen levels, respectively. Two strains of inbred albino rats, Fischer 344 (F344, resistant to OIR) and Sprague-Dawley rats (SD, susceptible to OIR), were used to assess the effect of rat strain on the stability of the small ncRNAs. Results In this rat model of OIR, 5S rRNA expression was variable with strain, fluctuations in oxygen levels, and developmental stage. U6 snRNA was stably expressed with changes in oxygen levels, and minimal variation was observed with strain and developmental stage. MiR-16 showed less stable expression with changes in oxygen levels and between strains compared to U6 snRNA. Some variation in expression in response to developmental stage was also observed. The PCR amplification efficiencies of the U6 snRNA and miR-16 TaqMan assays were 56% and 78%, respectively. U87 and 4.5S RNA (H) “Variant 1” expression varied with strain, exposure to cyclic hyperoxia, and in particular developmental stage, and was at low levels in the neonatal rat retina. Conclusions We conclude that U6 snRNA and miR-16 are the most suitable reference RNAs for normalizing miRNA expression, as they are relatively stable with strain, exposure to cyclic hyperoxia, and developmental stage in a rat model of OIR.
HEY2 mutations in malformed hearts

The basic helix‐loop‐helix (bHLH) transcription factor Hey2 (gridlock) is an important determinant of mammalian heart development, but its role in human ventricular septal defects is unknown. Hey2 functions as a repressor through the bHLH domain. By direct sequencing, we analyzed the sequences encoding the bHLH domain of the human HEY2 in 52 explanted hearts of unrelated patients with complex cardiac malformations, notably ventricular (VSD) and atrioventricular septal defects (AVSD). We found three nonsynonymous mutations, namely, c.286A>G (p.Thr96Ala), c.293A>C (p.Asp98Ala), and c.299T>C (p.Leu100Ser) affecting the second helix of HEY2 in the diseased cardiac tissues of two patients with AVSD. This result suggests a possible role of HEY2 in the regulation of ventricular septation in humans. Since the two AVSD patients carried also binding domain mutations in other cardiac‐specific transcription factors, e.g. NKX2‐5, TBX5, and GATA4, breakdown of combinatorial interactions of transcription factors may have contributed to the complexity of their cardiac malformations. © 2005 Wiley‐Liss, Inc.
Benign Breast Disease and the Risk of Subsequent Breast Cancer in African American Women

Benign breast disease (BBD) is an established risk factor for breast cancer among Caucasian women but less is known about BBD in African American women. As African American women suffer from disproportionate mortality due to breast cancer, special focus on pathologic characteristics that may influence disease risk is warranted. Benign breast biopsies from African American women were identified by the University Pathology Group (Detroit, MI). African American women of ages 20 to 84 years, who underwent a breast biopsy from 1997 to 2000, were eligible for the study. Subsequent breast cancers were identified through a linkage with the Detroit Surveillance Epidemiology and End Results (SEER) program. The first biopsy was reviewed by the pathologist, and lesions were classified following Dupont and Page criteria along with involution and other histologic features. Logistic regression was used to estimate the risk of developing a subsequent breast cancer with the histologic characteristics of BBD. A total of 1,406 BBD biopsies from African American women were included in this study with a median follow-up of 10.1 years. The majority (68%) showed nonproliferative disease, 29% had proliferative disease without atypia, and 3% had proliferative disease with atypia. Subsequent incident breast cancers occurred in 55 women (3.9%). Women whose biopsies showed proliferative disease with atypia were more than three-fold more likely to develop breast cancer as compared with women who had nonproliferative disease [relative risk (RR) 3.29, 95% confidence interval (CI) 1.21–8.93]. Better characterization of the risk of breast cancer among women with BBD, considering both ethnicity and detailed molecular findings, can lead to better surveillance, earlier diagnosis, and potentially improved survival. Cancer Prev Res; 5(12); 1375–80. ©2012 AACR.
The epigenetic imprinting defect of patients with Beckwith—Wiedemann syndrome born after assisted reproductive technology is not restricted to the 11p15 region

Background: Genomic imprinting refers to an epigenetic marking resulting in monoallelic gene expression and has a critical role in fetal development. Various imprinting diseases have recently been reported in humans and animals born after the use of assisted reproductive technology (ART). All the epimutations implicated involve a loss of methylation of the maternal allele (demethylation of KvDMR1/KCNQ1OT1 in Beckwith–Wiedemann syndrome (BWS), demethylation of SNRPN in Angelman syndrome and demethylation of DMR2/IGF2R in large offspring syndrome), suggesting that ART impairs the acquisition or maintenance of methylation marks on maternal imprinted genes. However, it is unknown whether this epigenetic imprinting error is random or restricted to a specific imprinted domain. Aim: To analyse the methylation status of various imprinted genes (IGF2R gene at 6q26, PEG1/MEST at 7q32, KCNQ1OT1 and H19 at 11p15.5, and SNRPN at 15q11–13) in 40 patients with BWS showing a loss of methylation at KCNQ1OT1 (11 patients with BWS born after the use of ART and 29 patients with BWS conceived naturally). Results: 3 of the 11 (27%) patients conceived using ART and 7 of the 29 (24%) patients conceived normally displayed an abnormal methylation at a locus other than KCNQ1OT1. Conclusions: Some patients with BWS show abnormal methylation at loci other than the 11p15 region, and the involvement of other loci is not restricted to patients with BWS born after ART was used. Moreover, the mosaic distribution of epimutations suggests that imprinting is lost after fertilisation owing to a failure to maintain methylation marks during pre-implantation development.
Heuristics to Classify Internet Backbone Traffic based on Connection Patterns

In this paper Internet backbone traffic is classified on transport layer according to network applications. Classification is done by a set of heuristics inspired by two previous articles and refined in order to better reflect a rough and highly aggregated backbone environment. Obvious misclassified flows by the existing two approaches are revealed and updated heuristics are presented, excluding the revealed false positives, but including missed P2P streams. The proposed set of heuristics is intended to provide researchers and network operators with a relatively simple and fast method to get insight into the type of data carried by their links. A complete application classification can be provided even for short 'snapshot' traces, including identification of attack and malicious traffic. The usefulness of the heuristics is finally shown on a large dataset of backbone traffic, where in the best case only 0.2% of the data is left unclassified.
Optimization and Deployment of Survivable Fiber-Wireless (FiWi) Access Networks with Integrated Small Cell and WiFi

Fiber-Wireless (FiWi) access network as a small cell backhaul is now becoming a promising architecture to satisfy the rapid growth of demand for mobile data traffic. With increasing amount of network traffic, the failure of network components such as distribution fiber link failure may lead to unpredictable service outages. The network survivability through protection and restoration has become a critical requirement. Thus, in this paper, we explore the protection mechanism for small cells by integrating WiFi and rerouting of data traffic over WiFi to offer some restoration of backhaul capacity. Using this architecture, we propose a novel method to optimize the deployment and maximize the coverage of survivable FiWi access network, with appropriate constraints from connectivity, survivability, capacity and delay perspectives. Our simulation results show the successful reconfiguration of survivable FiWi access networks with integrated small cell and WiFi under different simulated network failure scenarios and we demonstrate feasibility of the proposed optimization method.
HDF promise for the future

Sir, The February issue of Nephrology Dialysis Transplantation amply reported on online haemodiafiltration (HDF) as a possible promise for the future [1]. Please note the following erratum in Table 1 of the Editorial Comment, concerning our study with reference 16: high-volume HDF in postdilution was compared with high-flux haemodialysis (hfHD) with regard to the removal of beta2-microglobulin (b2M) and not with low-flux HD (lfHD), as is reported. Although most studies with online HDF demonstrate a higher removal of a broad range of the molecular spectrum of uraemic compounds versus HD, confusion still persists on the preferred method of HDF. With regard to the location of inflow of the substitution fluid, most studies rely on post-, pre-, mid- or mixed dilution, but this results in different removal rates. It is regrettable that in several references in the Editorial Comment, even the used HDF method was not mentioned (Table 1). Yet this is essential for the knowledge of the efficiency of the treatment. For instance, it is well known that with high-volume predilution HDF, a lower clearance of small molecules is achieved versus high-flux HD. Besides, a lower b2M clearance is noted in high-volume predilution HDF, compared with postdilution HDF with the same amount of substitution volume (80 ml/min) [2]. In view of these results, it is not surprising that in the ongoing trials in the Netherlands and France high-volume HDF in postdilution is chosen. It is also stated in the Editorial Comment that conflicting results concerning phosphate clearance were reported. When comparing phosphate removal with high-volume (100 ml/min) HDF in postdilution, our group observed a 19% higher removal versus high-flux HD [3]. Finally—as in our department, routine high-volume postdilution HDF is performed since 1993—in dialysis patients with more than 10 years of treatment, a lower prevalence of carpal tunnel syndrome is reported in reference 16 of the Editorial Comment. Concerning survival, recently our group reported a 26% survival benefit [4], comparable with the data of the DOPPS study and of the observational study from Eastern Europe. Conflict of interest statement. None declared.