Miracle-dz/UniFAR-FTUs huggingface dataset:
Analyzing single-lead short ECG recordings using dense convolutional neural networks and feature-based post-processing to detect atrial fibrillation

Objective: The prevalence of atrial fibrillation (AF) in the general population is 0.5%–1%. As AF is the most common sustained cardiac arrhythmia that is associated with an increased morbidity and mortality, its timely diagnosis is clinically desirable. The main aim of this study as our contribution to the PhysioNet/CinC Challenge 2017 was to develop an automatic algorithm for classification of normal sinus rhythm (NSR), AF, other rhythm (O), and noise using a short single-channel ECG. Furthermore, the impact of changing labels/annotations on performance of the proposed algorithm was studied in this article. Approach: The challenge training dataset (8528 ECG recordings) and a complementary dataset (6312 ECG recordings) from other sources were used for algorithm development. Version 3 (v3), which is an updated version of the annotations at the official phase of the challenge (v2), was used in this study. In the proposed algorithm, densely connected convolutional networks were combined with feature-based post-processing after initial signal quality analysis for the classification of ECG recordings. Main results: The F1 scores for classification of NSR, AF, and O were 0.91, 0.83, and 0.72, respectively, which led to a F1 of 0.82. There was a small or no performance difference between the top entries in the official phase of the challenge and our proposed method. An increase of 2.5% in F1 score was observed when the same annotations for training and test was used (using v3 annotations) compared to using different annotations (v2 annotations for training and v3 annotations for the test). Significance: Our promising results suggest that the availability of more data with improved labeling along with improvement in signal quality analysis make our algorithm suitable for practical clinical applications.
Developmentally regulated H2Av buffering via dynamic sequestration to lipid droplets in Drosophila embryos

Regulating nuclear histone balance is essential for survival, yet in early Drosophila melanogaster embryos many regulatory strategies employed in somatic cells are unavailable. Previous work had suggested that lipid droplets (LDs) buffer nuclear accumulation of the histone variant H2Av. Here, we elucidate the buffering mechanism and demonstrate that it is developmentally controlled. Using live imaging, we find that H2Av continuously exchanges between LDs. Our data suggest that the major driving force for H2Av accumulation in nuclei is H2Av abundance in the cytoplasm and that LD binding slows nuclear import kinetically, by limiting this cytoplasmic pool. Nuclear H2Av accumulation is indeed inversely regulated by overall buffering capacity. Histone exchange between LDs abruptly ceases during the midblastula transition, presumably to allow canonical regulatory mechanisms to take over. These findings provide a mechanistic basis for the emerging role of LDs as regulators of protein homeostasis and demonstrate that LDs can control developmental progression.
A History of the Pharmacological Treatment of Bipolar Disorder

In this paper, the authors review the history of the pharmacological treatment of bipolar disorder, from the first nonspecific sedative agents introduced in the 19th and early 20th century, such as solanaceae alkaloids, bromides and barbiturates, to John Cade’s experiments with lithium and the beginning of the so-called “Psychopharmacological Revolution” in the 1950s. We also describe the clinical studies and development processes, enabling the therapeutic introduction of pharmacological agents currently available for the treatment of bipolar disorder in its different phases and manifestations. Those drugs include lithium salts, valproic acid, carbamazepine, new antiepileptic drugs, basically lamotrigine and atypical antipsychotic agents (olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, asenapine, cariprazine and lurasidone). Finally, the socio-sanitary implications derived from the clinical introduction of these drugs are also discussed.
Alcohol dependence and very high risk level of alcohol consumption: a life‐threatening and debilitating disease

Women and men with alcohol dependence and very high risk drinking level (VHRDL; defined as drinking >60 or 100 g of ethanol per day, respectively) experience severe health consequences; however, data on the number of these individuals and their health risks are limited. This study estimated (1) the prevalence of VHRDL in 13 European Union (EU) countries among people 15–65 years of age, (2) the risk of disease and injury occurrence associated with VHRDL, (3) the proportion of deaths in nine EU countries attributable to VHRDL and (4) the life expectancy of people in France with VHRDL. Prevalence estimates of VHRDL were based on data obtained from clinical trials and the Global Information System on Alcohol and Health. The risk of disease and injury occurrence was estimated using microsimulations. Population‐attributable fractions (PAFs) were estimated using a Levin‐based methodology. The estimated prevalence of VHRDL in the 13 EU countries examined was 0.74–0.85 percent, with a disease and injury occurrence risk of 13.5 per 100 people with VHRDL per year. For the nine EU countries examined, VHRDL caused 53.6 percent of all liver cirrhosis, 43.8 percent of all pancreatitis and 41.1 percent of oral cavity and pharyngeal cancers (all other PAFs were below 30 percent). Applying these PAFs to French mortality data resulted in a life expectancy of 47–61 years for people with VHRDL—21–35 years less than the general population. These results indicate that the health burdens of VHRDL are potentially large, and interventions targeting VHRDL should be considered when formulating public health policies.
The Tumor Microenvironment of Epithelial Ovarian Cancer and Its Influence on Response to Immunotherapy

Immunotherapy as a treatment for cancer is a growing field of endeavor but reports of success have been limited for epithelial ovarian cancer. Overcoming the challenges to developing more effective therapeutic approaches lies in a better understanding of the factors in cancer cells and the surrounding tumor microenvironment that limit response to immunotherapies. This article provides an overview of some ovarian cancer cell features such as tumor-associated antigens, ovarian cancer-derived exosomes, tumor mutational burden and overexpression of immunoinhibitory molecules. Moreover, we describe relevant cell types found in epithelial ovarian tumors including immune cells (T and B lymphocytes, Tregs, NK cells, TAMs, MDSCs) and other components found in the tumor microenvironment including fibroblasts and the adipocytes in the omentum. We focus on how those components may influence responses to standard treatments or immunotherapies.
Numerical Simulation and Experimental Investigation of Cold-Rolled Steel Cutting

The paper presents results of the investigations on numerical computations and experimental verification concerning the influence of selected parameters of the cutting process on the stress state in bundles of cold-rolled steel sheets being cut using a guillotine. The physical model and, corresponding to it, the mathematical model of the analysed steel sheet being cut were elaborated. In this work, the relationship between the cutting depth and the values of reduced Huber–Mises stresses as well as the mechanism of sheet separation were presented. The numerical simulations were conducted by means of the finite element method and the computer system LS-DYNA. The results of numerical computations are juxtaposed as graphs, tables, and contour maps of sheet deformation as well as reduced Huber–Mises strains and stresses for selected time instants. The microscopic tests revealed two distinct zones in the fracture areas. The ductile and brittle zones are separated at the depth of ca. 1/3 thickness of the cut steel sheet.
Numerical Simulation and Experimental Validation of Sheet Laser Forming Processes Using General Scanning Paths

This work presents numerical simulations and an experimental validation of sheet laser forming processes using general scanning paths with different laser beam operating parameters (i.e., power, diameter, and scanning speed) in two specific graphite coated stainless steel blanks (i.e., with thicknesses of 0.3 mm and 0.6 mm for the AISI 302 and 304 alloys, respectively). To this end, three specific laser forming tests involving single S-shaped, multiple circular, and single piecewise linear scanning paths are carried out. On the other hand, the numerical simulation of these tests is performed via a coupled thermomechanical finite element formulation, accounting for large viscoplastic strains, temperature-dependent material properties, and convection-radiation phenomena. The final bending angles provided by this model are found to be in good agreement with the experimental measurements for all of the cases studied. Therefore, this modeling framework can be established as a reliable approach to predict the material thermomechanical response during sheet laser forming using general scanning paths.
Understanding Neurogastroenterology From Neuroimaging Perspective: A Comprehensive Review of Functional and Structural Brain Imaging in Functional Gastrointestinal Disorders

This review provides a comprehensive overview of brain imaging studies of the brain-gut interaction in functional gastrointestinal disorders (FGIDs). Functional neuroimaging studies during gut stimulation have shown enhanced brain responses in regions related to sensory processing of the homeostatic condition of the gut (homeostatic afferent) and responses to salience stimuli (salience network), as well as increased and decreased brain activity in the emotional response areas and reduced activation in areas associated with the top-down modulation of visceral afferent signals. Altered central regulation of the endocrine and autonomic nervous responses, the key mediators of the brain-gut axis, has been demonstrated. Studies using resting-state functional magnetic resonance imaging reported abnormal local and global connectivity in the areas related to pain processing and the default mode network (a physiological baseline of brain activity at rest associated with self-awareness and memory) in FGIDs. Structural imaging with brain morphometry and diffusion imaging demonstrated altered gray- and white-matter structures in areas that also showed changes in functional imaging studies, although this requires replication. Molecular imaging by magnetic resonance spectroscopy and positron emission tomography in FGIDs remains relatively sparse. Progress using analytical methods such as machine learning algorithms may shift neuroimaging studies from brain mapping to predicting clinical outcomes. Because several factors contribute to the pathophysiology of FGIDs and because its population is quite heterogeneous, a new model is needed in future studies to assess the importance of the factors and brain functions that are responsible for an optimal homeostatic state.
Speakers account for asymmetries in visual perspective so listeners don't have to

Debates over adults' theory of mind use have been fueled by surprising failures of visual perspective-taking in simple communicative tasks. Motivated by recent computational models of context-sensitive language use, we reconsider the evidence in light of the nuanced pragmatics of these tasks: the differential informativity expected of a speaker depending on the context. Our model predicts that cooperative speakers faced with asymmetries in visual access ought to adjust their utterances to be more informative. In Exp. 1, we explicitly manipulated the presence or absence of occlusions and found that speakers systematically produced longer, more specific referring expressions than required given their own view when they have uncertainty about what their partner is seeing. In Exp. 2, we compare the utterances used by confederates in prior work with those produced by unscripted speakers in the same task. We find that confederates are systematically less informative than expected, leading to more listener errors. In addition to demonstrating a sophisticated form of speaker perspective-taking, these results suggest a deeper pragmatic explanation for why listeners may sometimes neglect to consider visual perspective: Failures of visual perspective-taking may in fact be explained by sophisticated pragmatic expectations about communicative behavior---that is, to successful use of theory of mind.
Rural child malnutrition and unsuccessful outcome of food basket programme: does ethnicity matter?

ABSTRACT Objectives: The objectives of this study were to determine the prevalence of malnutrition among five-year-olds and factors associated with unsuccessful outcome of a Food Basket Programme (FBP) in a rural district of Kelantan, Malaysia. Design: Administrative health records from selected health clinics were reviewed. Study sample includes indigenous population or Orang Asli of Malaysia. Unsuccessful outcome was defined according to failure to complete the programme according to growth gain and on-time. Multiple logistics regression was used to assess the associated factors of unsuccessful outcome of FBP. Results: This study showed that the prevalence rates of malnutrition among children below five years old were 34.2% underweight, 16.4% thinness, 32.5% stunting and 3.0% overweight, with Orang Asli children faring the worse. Orang Asli children were also five times more likely to be unsuccessful in the FBP (p < .001). Conclusion: Malnutrition is still prevalent among children below five years old in this rural setting and Orang Asli children are vulnerable to have an unsuccessful outcome from the Food Basket Programme. Further research is necessary to further explain this association to inform policy, specifically for Orang Asli children.
Long‐noncoding RNA Atrolnc‐1 promotes muscle wasting in mice with chronic kidney disease

Chronic kidney disease (CKD) is commonly associated with cachexia, a condition that causes skeletal muscle wasting and an unfavourable prognosis. Although mechanisms leading to cachexia have been intensively studied, the advance of biological knowledges and technologies encourages us to make progress in understanding the pathogenesis of this disorder. Long noncoding RNAs (lncRNAs) are defined as >200 nucleotides RNAs but lack the protein‐coding potential. LncRNAs are involved in the pathogenesis of many diseases, but whether they functionally involve in muscle protein loss has not been investigated.
Loss of Nogo-A, encoded by the schizophrenia risk gene Rtn4, reduces mGlu3 expression and causes hyperexcitability in hippocampal CA3 circuits

Recent investigations of Nogo-A, a well characterized protein inhibitor of neurite outgrowth in the brain, have revealed additional functions including a role in neuropsychiatric disorders such as schizophrenia. Here we examined Nogo-A functions in mouse CA3 hippocampal circuitry. Patch clamp recordings showed that the absence of Nogo-A results in a hyperactive network. In addition, mGlu3 metabotropic glutamate receptors, which exhibit mutations in certain forms of schizophrenia, were downregulated specifically in the CA3 area. Furthermore, Nogo-A-/- mice showed disordered theta oscillations with decreased incidence and frequency, similar to those observed in mGlu3-/- mice. As disruptions in theta rhythmicity are associated with impaired spatial navigation, we tested mice using modified Morris water maze tasks. Mice lacking Nogo-A exhibited altered search strategies, displaying greater dependence on global as opposed to local reference frames. This link between Nogo-A and mGlu3 receptors may provide new insights into mechanisms underlying schizophrenia.
A method for estimating the deforestation timeline in rural settlements in a scenario of malaria transmission in frontier expansion in the Amazon Region

The Malaria Frontier Hypothesis (MFH) is the current model for predicting malaria emergence in the Brazilian Amazon. It has two important dimensions, ‘settlement time’ and ‘malaria incidence’, and its prediction are: malaria incidence peaks five years after the initiation of human settlement and declines towards zero after an estimated 10 years. Although MFH is currently accepted, it has been challenged recently. Herein, we described a novel method for estimating settlement timeline by using remote sensing technology integrated in an open-software geographic information system. Surprisingly, we found that of the majority of the rural settlements with high malaria incidence are more than 10 years old.
Implications of coronary artery calcium testing on risk stratification for lipid-lowering therapy according to the 2016 European Society of Cardiology recommendations: The MESA study

Aims The European Society of Cardiology (ESC) guideline on cardiovascular risk assessment considers coronary artery calcium a class B indication for risk assessment. We evaluated the degree to which coronary artery calcium can change the recommendation for individuals based on a change in estimated risk. Methods and results We stratified 5602 MESA participants according to the ESC recommendation as: no lipid-lowering treatment recommended (N = 2228), consider lipid-lowering treatment if uncontrolled (N = 1686), or lipid-lowering treatment recommended (N = 1688). We evaluated the ability of coronary artery calcium to reclassify cardiovascular risk. Among the selected sample, 54% had coronary artery calcium of zero, 25% had coronary artery calcium of 1–100 and 21% had coronary artery calcium greater than 100. In the lipid-lowering treatment recommended group 31% had coronary artery calcium of zero, while in the lipid-lowering treatment if uncontrolled group about 50% had coronary artery calcium of zero. The cardiovascular mortality rate was 1.7%/10 years in the lipid-lowering treatment if uncontrolled, and 7.0%/10 years in the lipid-lowering treatment recommended group. The absence of coronary artery calcium was associated with 1.4%/10 years in the lipid-lowering treatment if uncontrolled group and 3.0%/10 years in the lipid-lowering treatment recommended group. Compared with coronary artery calcium of zero, any coronary artery calcium was associated with significantly higher cardiovascular mortality in the lipid-lowering treatment recommended group (9.0%/10 years), whereas only coronary artery calcium greater than 100 was significantly associated with a higher cardiovascular mortality in the lipid-lowering treatment if uncontrolled group (3.2%/10 years). Conclusion The absence of coronary artery calcium is associated with a low incidence of cardiovascular mortality or coronary heart disease events even in individuals in whom lipid-lowering therapy is recommended. A significant proportion of individuals deemed to be candidates for lipid-lowering therapy might be reclassified to a lower risk group with the use of coronary artery calcium.
The Effects of Probiotic Supplementation on Gene Expression Related to Inflammation, Insulin and Lipid in Patients with Parkinson's Disease: A Randomized, Double-blind, PlaceboControlled Trial.

BACKGROUND This study was conducted to evaluate the effects of probiotic supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson's disease (PD). METHODS This randomized, double-blind, placebo-controlled clinical trial was conducted in 50 patients with PD as a pilot study. Participants were randomly allocated into two groups to take either 8×109 CFU/day probiotic supplements or placebo (n = 25 each group, one capsule daily) for 12 weeks. Gene expression related to inflammation, insulin, and lipid was quantified in peripheral blood mononuclear cells (PBMC) of PD patients, with RT-PCR method. RESULTS After the 12-week intervention, compared with the placebo, probiotic intake downregulated gene expression of interleukin-1 (IL-1) (P = 0.03), IL-8 (P < 0.001) and tumor necrosis factor alpha (TNF-α) (P=0.04) in PBMC of subjects with PD. In addition, probiotic supplementation upregulated transforming growth factor beta (TGF-β) (P = 0.02) and peroxisome proliferatoractivated receptor gamma (PPAR-γ) (P = 0.03) in PBMC of subjects with PD compared with the placebo. We did not observe any significant effect of probiotic intake on gene expression of low-density lipoprotein receptor (LDLR) and vascular endothelial growth factor (VEGF) in PBMC of patients with PD. CONCLUSION Overall, probiotics supplementation for 12 weeks in PD patients significantly improved gene expression of IL-1, IL-8, TNF-α, TGF-β and PPAR-γ, but did not affect gene expression of VEGF and LDLR, and biomarkers of inflammation and oxidative stress.
Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cells

Translation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we studied the link between translation and mRNA stability in embryonic stem cells (ESCs). Transcripts showed a wide range of stabilities, which correlated with their translation levels. The protein DHH1 links translation to mRNA stability in yeast; however loss of the mammalian homolog, DDX6, in ESCs did not disrupt the correlation across transcripts. Instead, the loss of DDX6 led to upregulated translation of microRNA targets, without concurrent changes in mRNA stability. The Ddx6 knockout cells were phenotypically and molecularly similar to cells lacking all microRNAs (Dgcr8 knockout ESCs). These data show that the loss of DDX6 can separate the two canonical functions of microRNAs: translational repression and transcript destabilization. Furthermore, these data uncover a central role for translational repression independent of transcript destabilization in defining the downstream consequences of microRNA loss.
Moleculer dynamics simulaiton revealed reciever domain of Acinetobacter baumannii BfmR enzyme as the hot spot for future antibiotics designing

Abstract Acinetobacter baumannii is an alarming nosocomial pathogen that is resistant to multiple drugs. The pathogen is forefront of scientific attention because of high mortality and morbidity found for its complications in the past decade. As a consequence, identification of novel drug candidates and subsequent designing of novel chemical scaffolds is an imperative need of time. In the present study, we used a recently reported structure of BfmR enzyme and performed structure based virtual screening, MD simulation and binding free energies calculations. MD simulation revealed a profound movement of the best-characterized inhibitor towards the α4-β5-α5 face of the enzyme receiver domain, thus indicating its high affinity for this site compared to phosphorylation. Furthermore, it was observed that the enzyme and enzyme-inhibitor complex have high structure stability with mean RMSD of 1.2 and 1.1 Å, respectively. Binding free energy calculations for the complex unraveled high stability with MMGBSA score of −26.21 kcal/mol and MMPBSA score of −1.47 kcal/mol. Van der Waal energy was found highly favorable with value of −30.25 kcal/mol and dominated significantly the overall binding energy. Furthermore, a novel WaterSwap assay was used to circumvent the limitations of MMGB/PBSA that complements the inhibitor affinity for enzyme active pocket as depicted by the low convergence of Bennett, TI and FEP algorithms. Results yielded from this study will not only give insight into the phenomena of inhibitor movement towards the enzyme receiver domain, but will also provide a useful baseline for designing derivatives with improved biological and pharmacokinetics profiles. Communicated by Ramaswamy H. Sarma