Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk factors for sudden cardiac death in childhood hypertrophic cardiomyopathy: A systematic review and meta-analysis

Aims To perform a systematic literature review and meta-analysis of clinical risk factors for sudden cardiac death (SCD) in childhood hypertrophic cardiomyopathy. Methods Medline and PubMed databases were searched for original articles published in English from 1963 through to December 2015 that included patients under 18 years of age with a primary or secondary end-point of either SCD or SCD-equivalent events (aborted cardiac arrest or appropriate implantable cardioverter–defibrillator discharge) or cardiovascular death (CVD). Results Twenty-five studies (3394 patients) met the inclusion criteria. We identified four conventional major risk factors that were evaluated in at least four studies and that we found to be statistically associated with an increased risk of death in at least two studies: previous adverse cardiac event (pooled hazard ratio [HR] 5.4, 95% confidence interval [CI] 3.67–7.95, p < 0.001); non-sustained ventricular tachycardia (pooled HR 2.13, 95% CI 1.21–3.74, p = 0.009); unexplained syncope (pooled HR 1.89, 95% CI 0.69–5.16, p = 0.22); and extreme left ventricular hypertrophy (pooled HR 1.80, 95% CI 0.75–4.32, p = 0.19). Left atrial diameter did not meet the major risk factor criteria; however, this is likely to be an additional significant risk factor. ‘Minor’ risk factors included a family history of SCD, gender, age, symptoms, electrocardiogram changes, abnormal blood pressure response to exercise and left ventricular outflow tract obstruction. Conclusions A lack of well-designed, large, population-based studies in childhood hypertrophic cardiomyopathy means that the evidence base for individual risk factors is not robust. We have identified four clinical parameters that are likely to be associated with increased risk of SCD, SCD-equivalent events or CVD. Multi-centre prospective studies are needed in order to further determine the relevance of these factors in predicting SCD in childhood hypertrophic cardiomyopathy and to identify novel risk markers. Condensed abstract A systematic review and meta-analysis of clinical risk factors predicting sudden cardiac death in childhood hypertrophic cardiomyopathy was performed, identifying four ‘major’ factors: previous adverse cardiac event; non-sustained ventricular tachycardia; syncope; and extreme left ventricular hypertrophy. Well-designed multi-centre studies are required in the future in order to confirm these findings.
Management Education for Clinical Directors: An Evaluation

Based on a national evaluation of a £2 million Government‐sponsored programme to send some 260 consultants from the 14 Regional Health Authorities in England to attend Business School management programmes during 1992‐3. Reports on a 20‐month tracking study to assess changes in the level and breadth of knowledge, attitudes and behaviour as acknowledged by course participants, their UGMs, line managers and where possible their chief executives. Over 2,000 course participants were interviewed and some 106 completed both pre‐ and post‐course attendance “self‐efficacy” questionnaires. Most consultants emerged from the courses feeling more confident to handle their current and prospective management roles and the tangible returns to the organization suggest that advanced management development should continue for consultants being appointed to senior management roles such as clinical and medical directors.
Finite temperature multiscale computational modeling of materials at nanoscale

The A multiscale computational method (CADD) is presented for modeling of materials at nanoscale whereby a continuum region containing defects is coupled to a fully atomistic region. The method reduces the degree of freedom in simulations of mechanical behavior of nanomaterials without sacrificing important physics. Applications to nanoindentation are used to validate and demonstrate the capabilities of the model.
Myocardin-Related Transcription Factor A Is a Common Mediator of Mechanical Stress- and Neurohumoral Stimulation-Induced Cardiac Hypertrophic Signaling Leading to Activation of Brain Natriuretic Peptide Gene Expression

ABSTRACT Subjecting cardiomyocytes to mechanical stress or neurohumoral stimulation causes cardiac hypertrophy characterized in part by reactivation of the fetal cardiac gene program. Here we demonstrate a new common mechanism by which these stimuli are transduced to a signal activating the hypertrophic gene program. Mechanically stretching cardiomyocytes induced nuclear accumulation of myocardin-related transcription factor A (MRTF-A), a coactivator of serum response factor (SRF), in a Rho- and actin dynamics-dependent manner. Expression of brain natriuretic peptide (BNP) and other SRF-dependent fetal cardiac genes in response to acute mechanical stress was blunted in mice lacking MRTF-A. Hypertrophic responses to chronic pressure overload were also significantly attenuated in mice lacking MRTF-A. Mutation of a newly identified, conserved and functional SRF-binding site within the BNP promoter, or knockdown of MRTF-A, reduced the responsiveness of the BNP promoter to mechanical stretch. Nuclear translocation of MRTF-A was also involved in endothelin-1- and angiotensin-II-induced activation of the BNP promoter. Moreover, mice lacking MRTF-A showed significantly weaker hypertrophic responses to chronic angiotensin II infusion than wild-type mice. Collectively, these findings point to nuclear translocation of MRTF-A as a novel signaling mechanism mediating both mechanical stretch- and neurohumoral stimulation-induced BNP gene expression and hypertrophic responses in cardiac myocytes.
HuR Uses AUF1 as a Cofactor To Promote p16INK4 mRNA Decay

ABSTRACT In this study, we show that HuR destabilizes p16INK4 mRNA. Although the knockdown of HuR or AUF1 increased p16 expression, concomitant AUF1 and HuR knockdown had a much weaker effect. The knockdown of Ago2, a component of the RNA-induced silencing complex (RISC), stabilized p16 mRNA. The knockdown of HuR diminished the association of the p16 3′ untranslated region (3′UTR) with AUF1 and vice versa. While the knockdown of HuR or AUF1 reduced the association of Ago2 with the p16 3′UTR, Ago2 knockdown had no influence on HuR or AUF1 binding to the p16 3′UTR. The use of EGFP-p16 chimeric reporter transcripts revealed that p16 mRNA decay depended on a stem-loop structure present in the p16 3′UTR, as HuR and AUF1 destabilized EGFP-derived chimeric transcripts bearing wild-type sequences but not transcripts with mutations in the stem-loop structure. In senescent and HuR-silenced IDH4 human diploid fibroblasts, the EGFP-p16 3′UTR transcript was more stable. Our results suggest that HuR destabilizes p16 mRNA by recruiting the RISC, an effect that depends on the secondary structure of the p16 3′UTR and requires AUF1 as a cofactor.
Listening to unanimated objects' stories for treatment and repair: A computer vision approach

In any medical practice an important part of the treatment strategy includes listening to what a patient has to say. Considering a broken object as a subject of treatment, we claim that listening to an object's story provide an aid to its repair. A prominent question emerges hence: how can objects tell their stories? Based on the consideration that an object's story corresponds to its peculiar lifecycle, we are confident that it can be acquired by “observing” how that object is crafted, manipulated and operated along its life. Two sweaters, for example, may be exactly the same at the beginning, but depending on how they have been worn, and on the decay process to which they have been subjected, their correspondent stories may be very different. With this in mind, we have tried to exploit fine gesture recognition algorithms that have been put to good use to capture the stories of unanimated objects that are crafted and then manipulated by human beings. This approach appears very promising when searching for mechanisms capable of automatically understand what objects have to tell to us.
Escitalopram in clinical practice in Greece: treatment response and tolerability in depressed patients

Objective: To evaluate the effectiveness and tolerability of escitalopram (10-20 mg/day) in adult outpatients suffering from major depressive disorder in naturalistic settings. Methods: An open-label, 3-month, surveillance study was conducted in 434 investigative sites in Greece enrolling 5175 patients. Clinical Global Impression-Severity (CGI-S) scale and patient-rated Sheehan Disability Scale (SDS) were used as efficacy measurements and treatment discontinuation rates due to adverse events was used to assess tolerability. Results: Clinically significant improvement in CGI-S scores was recorded after 3 months. At baseline, patients reported marked or extreme disability for work (38%), social life (41%) and family life (37%), whereas after 3 months of treatment, 80.6%, 79.5% and 83.5% of patients indicated either no or mild disability, respectively. Escitalopram had good tolerability, demonstrated by a very low rate of discontinuations due to adverse events. Conclusion: In this large naturalistic study, escitalopram was well tolerated and improved both depressive symptoms and function.
MLL Associates with Telomeres and Regulates Telomeric Repeat-Containing RNA Transcription

ABSTRACT Mammalian telomeres consist of TTAGGG repeats organized in nucleosomes and associated with a six-protein complex known as shelterin, which preserves telomere structure and protects chromosome ends from the cellular DNA damage response. Recent studies have found that telomeres are transcribed into telomeric UUAGGG repeat-containing RNA (TERRA) starting from subtelomeric regions. TERRA binding at telomeres appears to be involved in cis-based mechanisms of telomeric chromatin organization and maintenance. A number of histone methyltransferases (HMTs) are known to influence telomeric chromatin status; however, the regulatory mechanisms of telomere transcription are poorly understood. Here, we show that the histone 3/lysine 4 (H3/K4) HMT and the transcriptional regulator MLL associate with telomeres and contribute to their H3/K4 methylation and transcription in a telomere length-dependent manner. In human diploid fibroblasts, RNA interference-mediated MLL depletion affects telomere chromatin modification and transcription and induces the telomere damage response. Telomere uncapping through either TRF2 shelterin protein knockdown or exposure to telomere G-strand DNA oligonucleotides significantly increases the transcription of TERRA, an effect mediated by the functional cooperation between MLL and the tumor suppressor p53. In total, our findings identify a previously unrecognized role of MLL in modifying telomeric chromatin and provide evidence for the functional interaction between MLL, p53, and the shelterin complex in the regulation of telomeric transcription and stability.
Growth and maturation of Sereer adolescent girls (Senegal) in relation to seasonal migration for labor

This study compares the growth and maturity status of Sereer girls (Senegal) temporarily migrating to an urban setting during the dry season to work as maids in the capital city, Dakar, with girls remaining in rural communities. A total of 343 girls, aged 12.5–14.5 were surveyed: 222 lived year‐round in several villages (sedentes) and 121 girls worked in Dakar for 8 months of the year (migrants). All girls were born and reared under the same conditions and in the same rural communities in Senegal. Growth and nutritional status were assessed with anthropometry, and the body mass index (BMI) was calculated. Sexual maturation was assessed by stage of breast development and occurrence of menarche. A questionnaire on housing conditions, food consumption patterns, nature of work, health status, and reasons for leaving the villages was administered to 57 urban girls. Overall, the girls were small relative to NCHS/WHO reference values: 30–40% were lower than −2 z‐scores of age‐specific medians. They also had less subcutaneous fat. Only nine girls had attained menarche and 30% were prepubertal in breast development. The migrants had a significantly higher body mass and BMI and thicker skinfolds than sedentes, but there was no difference in stature. The migrants were also more sexually mature than the sedentes. Comparison of anthropometric status 2 years before migration, in 1995, showed no differences between migrant and sedentes girls. Within migrant girls, those with two or more stays in Dakar were taller and heavier than newcomers. These results suggest that seasonal movement to the city results in improved nutritional status, as reflected in larger body mass and increased fatness. These factors appear to be associated with better living conditions in the city. Am. J. Hum. Biol. 11:539–550, 1999. © 1999 Wiley‐Liss, Inc.
Smoking Attenuates the Beneficial Effect of Physical Activity on Intima-Media Thickness of Carotid Artery in Young and Middle-Aged Smokers

Background : Though the favorable effect of physical activity and the hazardous effect of smoking on the progression of atherosclerosis have been well studied, the interactive effect of the two factors has seldom been investigated. Methods : A total of 1,090 subjects from among examinees of screening for brain diseases (an annual medical checkup of the brain) from April 2007 to March 2008 were studied to clarify the effect of physical activity on current, former and never smokers in relation to maximum carotid intima-media thickness (IMT). Univariate and multivariate analyses were performed to investigate the relationship between maximum IMT and independent variables such as age, gender, coexisting disease, physical activity, alcohol drinking, family history, symptoms, BMI, systolic blood pressure, diastolic blood pressure, blood sugar, total cholesterol, HDL cholesterol, triglyceride, Bathel index and time since smoking cessation. Results : Univariate analysis revealed that only never smokers exhibited a significant relationship between physical activity and maximum IMT. Multiple regression analyses performed for three age specific groups ( ≤ 49, 50 - 59, ≥ 60), demonstrated that physical activity was not a significant predictor of maximum IMT in current and former smokers 49 years old and younger, and current smokers 50 - 59 years old, though the other multivariate analyses showed no meaningful results, including for never smokers. Conclusions : The present study revealed that for young and middle-aged current smokers, the favorable effect of physical activity on the prevention of carotid atherosclerosis might be attenuated by detrimental effect of smoking. doi:10.4021/jnr74w
Unperturbed Immune Function despite Mutation of C-Terminal Tyrosines in Syk Previously Implicated in Signaling and Activity Regulation

ABSTRACT The nonreceptor tyrosine kinase Syk, a central regulator of immune cell differentiation and activation, is a promising drug target for treatment of leukemia and allergic and inflammatory diseases. The clinical failure of Syk inhibitors underscores the importance of understanding the regulation of Syk function and activity. A series of previous studies emphasized the importance of three C-terminal tyrosines in Syk for kinase activity regulation, as docking sites for downstream effector molecules, and for Ca2+ mobilization. Here, we investigated the roles of these C-terminal tyrosines in the mouse. Surprisingly, expression of a triple tyrosine-to-phenylalanine human Syk mutant, SYK(Y3F), was not associated with discernible signaling defects either in reconstituted DT40 cells or in B or mast cells from mice expressing SYK(Y3F) instead of wild-type Syk. Remarkably, lymphocyte differentiation, calcium mobilization, and 2,4,6-trinitrophenyl (TNP)-specific immune responses were unperturbed in SYK(Y3F) mice. These results emphasize the capacity of immune cells to compensate for specific molecular defects, likely using redundant intermolecular interactions, and highlight the importance of in vivo analyses for understanding cellular signaling mechanisms.
A Randomly Integrated Transgenic H19 Imprinting Control Region Acquires Methylation Imprinting Independently of Its Establishment in Germ Cells

ABSTRACT The imprinted expression of the mouse Igf2/H19 locus is governed by the differential methylation of the imprinting control region (ICR), which is established initially in germ cells and subsequently maintained in somatic cells, depending on its parental origin. By grafting a 2.9-kbp H19 ICR fragment into a human β-globin yeast artificial chromosome in transgenic mice, we previously showed that the ICR could recapitulate imprinted methylation and expression at a heterologous locus, suggesting that the H19 ICR in the β-globin locus contained sufficient information to maintain the methylation mark (K. Tanimoto, M. Shimotsuma, H. Matsuzaki, A. Omori, J. Bungert, J. D. Engel, and A. Fukamizu, Proc. Natl. Acad. Sci. USA 102:10250-10255, 2005). Curiously, however, the transgenic H19 ICR was not methylated in sperm, which was distinct from that seen in the endogenous locus. Here, we reevaluated the ability of the H19 ICR to mark the parental origin using more rigid criteria. In the testis, the methylation levels of the solitary 2.9-kbp transgenic ICR fragment varied significantly between six transgenic mouse lines. However, in somatic cells, the paternally inherited ICR fragment exhibited consistently higher methylation levels at five out of six randomly integrated sites in the mouse genome. These results clearly demonstrated that the H19 ICR could acquire parent-of-origin-dependent methylation after fertilization independently of the chromosomal integration site or the prerequisite methylation acquisition in male germ cells.
The impact of distal embolization and distal protection on long-term outcome in patients with ST elevation myocardial infarction randomized to primary percutaneous coronary intervention – results from a randomized study

Objectives: The impact of angiographically visible distal embolization (DE) and distal protection occurring during primary percutaneous coronary intervention (PCI) on long-term outcome has not been studied in a contemporary ST-segment elevation myocardial infarction (STEMI) cohort. To evaluate the association between DE and long-term outcome in STEMI patients treated with primary PCI with or without distal protection. Methods and results: In this post-hoc analysis of a randomized study, 591 STEMI patients were randomized to conventional primary PCI or primary PCI with distal protection and followed for 5 years. There was no statistically significant difference in MACE rate between patients treated with or wthout distal protection (19% versus 25%; p=0.10). There seemed to be interaction between distal protection and DE in major adverse cardiac events (MACE) (p=0.08), mortality (p=0.02) and reinfarction (p=0.06), but not admission for heart failure (p=0.40). DE was related to increased risk of admission for heart failure independently of distal protection (12.0% versus 5.0; p=0.015). The MACE rate for patients treated with standard PCI with DE was 31.3% compared to 24.8% for patients without DE (p=0.30), and 44.4% for patients treated with distal protection with DE compared to 17.9% for patients without DE (p=0.005). DE was not related to mortality (p=0.52) or reinfarction (p=0.52) among patients treated with standard PCI, but was related to higher rates of mortality (p=0.012) and reinfarction (p=0.008) when distal protection was used. Conclusion: DE occurred in 11% of STEMI patients treated with conventional primary PCI, and was associated with increased risk of development of heart failure. Distal protection did not improve the 5-years MACE rate, and might even aggravate the prognosis following DE, but this should only be considered hypothesis-generating.
TF-ICF: A New Term Weighting Scheme for Clustering Dynamic Data Streams

In this paper, we propose a new term weighting scheme called term frequency-inverse corpus frequency (TF-ICF). It does not require term frequency information from other documents within the document collection and thus, it enables us to generate the document vectors of N streaming documents in linear time. In the context of a machine learning application, unsupervised document clustering, we evaluated the effectiveness of the proposed approach in comparison to five widely used term weighting schemes through extensive experimentation. Our results show that TF-ICF can produce document clusters that are of comparable quality as those generated by the widely recognized term weighting schemes and it is significantly faster than those methods
Comparative Analysis of the Impact of Discretization on the Classification with Naïve Bayes and Semi-Naïve Bayes Classifiers

While data could be discrete and continuous (defined as ordinal numerical features), some classifiers, like Naive Bayes (NB), work only with or may perform better with the discrete data. We focus on NB due to its popularity and linear training time. We investigate the impact of eight discretization algorithms (Equal Width, Equal Frequency, Maximum Entropy, IEM, CADD, CAIM, MODL, and CACC) on the classification with NB and two modern semi-NB classifiers, LBR and AODE.Our comprehensive empirical study indicates that unsupervised discretization algorithms are the fastest while among the supervised algorithms the fastest is maximum entropy, followed by CAIM and IEM. The CAIM and MODL discretizers generate the lowest and the highest number of discrete values, respectively.We compare the time to build the classification model and classification accuracy when using raw and discretized data. We show that discretization helps to improve the classification with the NB when compared with flexible NB which models continuous features using Gaussian kernels. The AODE classifier obtains on average the best accuracy, while the best performing setup includes discretization with IEM and classification with AODE. The runner-up setups include CAIM and CACC coupled with AODE and CAIM and IEM coupled with LBR. IEM and CAIM are shown to provide statistically significant improvements across all considered datasets for LBR and AODE classifiers when compared with using NB on the continuous data. We also show that the improved accuracy comes at the trade-off of substantially increased runtime.
Optimal Superimposed Training Design for Spatially Correlated Fading MIMO Channels

The problem of channel estimation for spatially correlated fading multiple-input multiple-output (MIMO) systems is considered. Based on the channel's second order statistic, the minimum mean-square error (MMSE) channel estimator that works with the superimposed training signal is first developed. The problem of designing the optimal superimposed signal is then addressed and solved with an iterative optimization algorithm. Results show that under the constraint of equal training power and bandwidth efficiency, our optimal design of the superimposed training signal leads to a significant reduction in channel estimation error when compared to the conventional design of time-multiplexing training, especially for slowly time-varying channels with a large coherence time. The issue of power allocation between the information-bearing and training signals for detection enhancement is also investigated. Simulation results demonstrate excellent bit-error-rate performance of orthogonal space-time block codes with our proposed channel estimation.