Miracle-dz/UniFAR-FTUs huggingface dataset:
Excess coronary artery disease risk in South Asian immigrants: Can dysfunctional high-density lipoprotein explain increased risk?

Background: Coronary artery disease (CAD) is the leading cause of mortality and morbidity in the United States (US), and South Asian immigrants (SAIs) have a higher risk of CAD compared to Caucasians. Traditional risk factors may not completely explain high risk, and some of the unknown risk factors need to be explored. This short review is mainly focused on the possible role of dysfunctional high-density lipoprotein (HDL) in causing CAD and presents an overview of available literature on dysfunctional HDL. Discussion: The conventional risk factors, insulin resistance parameters, and metabolic syndrome, although important in predicting CAD risk, may not sufficiently predict risk in SAIs. HDL has antioxidant, antiinflammatory, and antithrombotic properties that contribute to its function as an antiatherogenic agent. Recent Caucasian studies have shown HDL is not only ineffective as an antioxidant but, paradoxically, appears to be prooxidant, and has been found to be associated with CAD. Several causes have been hypothesized for HDL to become dysfunctional, including Apo lipoprotein A-I (Apo A-I) polymorphisms. New risk factors and markers like dysfunctional HDL and genetic polymorphisms may be associated with CAD. Conclusions: More research is required in SAIs to explore associations with CAD and to enhance early detection and prevention of CAD in this high risk group.
Bmc Molecular Biology Identification of Two Regulatory Binding Sites Which Confer Myotube Specific Expression of the Mono-adp-ribosyltransferase Art1 Gene

Background: Mono-ADP-ribosyltransferase (ART) 1 belongs to a family of mammalian ectoenzymes that catalyze the transfer of ADP-ribose from NAD + to a target protein. ART1 is predominantly expressed in skeletal and cardiac muscle. It ADP-ribosylates α7-integrin which together with β1-integrin forms a dimer and binds to laminin, a protein of the extracellular matrix involved in cell adhesion. This posttranslational modification leads to an increased laminin binding affinity.
Transient Darwinian selection in Salmonella enterica serovar Paratyphi A during 450 years of global spread of enteric fever

Significance The most recent common ancestor of Paratyphi A, one of the most common causes of enteric fever, existed approximately 450 y ago, centuries before that disease was clinically recognized. Subsequent changes in the genomic sequences included multiple mutations and acquisitions or losses of genes, including bacteriophages and genomic islands. Some of those evolutionary changes were reliably attributed to Darwinian selection, but that selection was only transient, and many genetic changes were subsequently lost because they rendered the bacteria less fit (purifying selection). We interpret the history of Paratyphi A as reflecting drift rather than progressive evolution and suggest that most recent increases in frequencies of bacterial diseases are due to environmental changes rather than the novel evolution of pathogenic bacteria. Multiple epidemic diseases have been designated as emerging or reemerging because the numbers of clinical cases have increased. Emerging diseases are often suspected to be driven by increased virulence or fitness, possibly associated with the gain of novel genes or mutations. However, the time period over which humans have been afflicted by such diseases is only known for very few bacterial pathogens, and the evidence for recently increased virulence or fitness is scanty. Has Darwinian (diversifying) selection at the genomic level recently driven microevolution within bacterial pathogens of humans? Salmonella enterica serovar Paratyphi A is a major cause of enteric fever, with a microbiological history dating to 1898. We identified seven modern lineages among 149 genomes on the basis of 4,584 SNPs in the core genome and estimated that Paratyphi A originated 450 y ago. During that time period, the effective population size has undergone expansion, reduction, and recent expansion. Mutations, some of which inactivate genes, have occurred continuously over the history of Paratyphi A, as has the gain or loss of accessory genes. We also identified 273 mutations that were under Darwinian selection. However, most genetic changes are transient, continuously being removed by purifying selection, and the genome of Paratyphi A has not changed dramatically over centuries. We conclude that Darwinian selection is not responsible for increased frequency of enteric fever and suggest that environmental changes may be more important for the frequency of disease.
A factuality profiler for eventualities in text

Event factuality is the level of information expressing the factual status of eventualities mentioned in text. That is, it conveys whether eventualities are characterized as corresponding to facts, to possibilities, or to situations that do not hold in the world. As such, it touches on two categories more standardly assumed in the literature: modality and evidentiality. They both have been widely discussed in linguistics and philosophy, but it is not until recently that have started to receive some attention within the area of NLP. Factuality is a necessary component for reasoning about eventualities in discourse. Inferences derived from events that have not happened, or that are possible, are different from those derived from events judged as factual. It is also essential for any task involving temporal ordering. The creation of event timelines needs to be aware of the different status of eventualities presented as uncertain or counterfactual. My dissertation aims at designing and developing a factuality profiler, namely a tool devoted to the identification of the factuality degree associated to eventualities mentioned in discourse. Event factuality cannot be conceived independently from language users, who are understood here as the sources of factuality information. Their inclusion in the model is fundamental. Two sources can assign different factuality values to the same event. Because of that, the factuality profiler must be capable of representing different and possibly contradictory information about the factuality nature of any event. De Facto, the tool I am presenting here, is grounded on the linguistic strategies we speakers employ to signal degrees of factuality in discourse. These involve information at different levels: lexical, syntactic, and rhetoric. De Facto implements an algorithm based on the grammatical structuring of factuality in languages like English, and is informed with a set of linguistic resources compiled from a data-driven approach. For evaluating De Facto, I created FactBank, a corpus annotated with factuality information. The interannotation agreement score for the task of assigning factuality values to events is kcohen = 0.81. Running De Facto against the gold standard results in F1=0.74 (macro-averaging), F1=0.85 (micro-averaging) and, in terms of interannotation agreement, kcohen =0.72.
How Is Clinical Reasoning Developed, Maintained, and Objectively Assessed? Views from Expert Internists and Internal Medicine Interns

Introduction: There is limited understanding of how clinical reasoning is developed, maintained, and objectively assessed. Using the theoretical lens of deliberate practice, we explored physicians' views on clinical reasoning. We compared responses from internists (faculty) and internal medicine interns, to identify potential qualitative and/or quantitative differences in how clinical reasoning is developed and maintained. Methods: Participants' free‐text comments regarding how clinical reasoning is developed, maintained, and objectively assessed were analyzed. Three investigators coded responses using a constant‐comparative, grounded theory approach. We also compared the frequencies of each theme between the 2 groups. Results: Twenty‐two faculty and 17 interns participated in this study. Faculty and intern themes for how clinical reasoning is developed, maintained, and objectively assessed were similar, but quantitative and qualitative differences emerged. Interrater reliability of themes was high (overall kappa: 0.92; range: 0.88‐0.98). Only experts (faculty) mentioned the value of teaching for development and maintenance of clinical reasoning. Interns focused on knowledge acquisition activities and use of online resources. Experts and intern participants both struggled with how to best measure clinical reasoning; direct observation was rarely mentioned as a strategy. Discussion: Consistent with our theoretical expectations, we found quantitative and qualitative differences in participants' responses, which have implications for teaching and assessment of clinical reasoning. By capturing the types of activities and their relative frequencies within and between these groups, this work adds to the deliberate practice literature.
Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research

Much of our knowledge of the endocannabinoid system in schizophrenia comes from behavioral measures in rodents, like prepulse inhibition of the acoustic startle and open-field locomotion, which are commonly used along with neurochemical approaches or drug challenge designs. Such methods continue to map fundamental mechanisms of sensorimotor gating, hyperlocomotion, social interaction, and underlying monoaminergic, glutamatergic, and GABAergic disturbances. These strategies will require, however, a greater use of neurophysiological tools to better inform clinical research. In this sense, electrophysiology and viral vector-based circuit dissection, like optogenetics, can further elucidate how exogenous cannabinoids worsen (e.g., tetrahydrocannabinol, THC) or ameliorate (e.g., cannabidiol, CBD) schizophrenia symptoms, like hallucinations, delusions, and cognitive deficits. Also, recent studies point to a complex endocannabinoid-endovanilloid interplay, including the influence of anandamide (endogenous CB1 and TRPV1 agonist) on cognitive variables, such as aversive memory extinction. In fact, growing interest has been devoted to TRPV1 receptors as promising therapeutic targets. Here, these issues are reviewed with an emphasis on the neurophysiological evidence. First, we contextualize imaging and electrographic findings in humans. Then, we present a comprehensive review on rodent electrophysiology. Finally, we discuss how basic research will benefit from further combining psychopharmacological and neurophysiological tools.
Forecaster performance evaluation with cross-validation and variants

In time series prediction, there is currently no consensus for a best practice of how predictors should be compared and evaluated. We investigate this issue through an empirical study. First, we discuss forecast types, error calculation, and error averaging methods in use, and then we focus on model selection procedures. We consider using ordinary cross-validation techniques and the common time series approach of choosing a test set from the end of a series, as well as less common approaches such as non-dependent cross-validation or blocked cross-validation. The study uses different error measures, various machine learning methods, and synthetic time series data. The results indicate that cross-validation can be a useful tool also in time series evaluation. Theoretical problems can be prevented by using it in the blocked form.
Origins and consequences of centrosome aberrations in human cancers

Recent years have seen a revival of interest in the possible contribution of centrosomes to the development of human cancers. The underlying hypothesis, formulated almost 100 years ago (Boveri T. The origin of malignant tumors; Baltimore, MD: Williams and Wilkins, 1929.), states that numerical and/or structural centrosome abnormalities will cause me missegregation. In addition, centrosome abnormalities are expected to affect cell shape, polarity, and motility. Thus, deregulation of centrosome number and function may foster both chromosomal instability and loss of tissue architecture—2 of the most common phenotypes associated with solid human tumors. In support of the role of centrosome deregulation in tumorigenesis, centrosome aberrations have been observed in early, premalignant lesions. Moreover, they are frequent in many different types of common tumors and their prominence often correlates with poor clinical outcome. This review addresses the origins of centrosome aberrations in human tumors as well as the expected impact of centrosome aberrations on cell fate and tumor development. © 2006 Wiley‐Liss, Inc.
Assessment of Cardiac Function Using Multidetector Row Computed Tomography

Abstract: In patients with suspected or documented heart disease, a precise quantitative and qualitative assessment of cardiac function is critical for clinical diagnosis, risk stratification, management and prognosis. Cardiac CT is increasingly being used in diagnosis of coronary artery disease. Initially multi-detector row computed tomography (MDCT) was used chiefly for detecting coronary artery stenosis and assessment of cardiac morphology. Electron beam computed tomography has been shown to provide a highly accurate ejection fraction (±1%), with 50 ms image acquisition per image. Retrospective electrocardiographic gating allows for image reconstruction in any phase of the cardiac cycle. Thus, end systolic and end diastolic images can be produced to assess ventricular volumes and function. Despite lower temporal resolution than electron beam computed tomography, the ability of MDCT to assess ejection fraction is preserved. In the assessment of cardiac function, MDCT has been shown to be in good agreement with echocardiography, cineventriculography, single photon emission computed tomography and magnetic resonance imaging. The fast technical development of scanner hardware along with multisegmental image reconstruction has led to rapid improvement of spatial and temporal resolution and significantly faster cardiac scans. The same data that is acquired for MDCT angiography can also be used for evaluation of cardiac function. Considering contrast media application, radiation exposure, and limited temporal resolution, MDCT solely for analysis of cardiac function parameters seems not reasonable at the present time. However, because the data is already obtained during coronary evaluation, the combination of noninvasive coronary artery imaging and assessment of cardiac function with MDCT is a suitable approach to a conclusive cardiac workup in patients with suspected coronary artery disease. MDCT seems suitable for assessment of cardiac function by MDCT when results are held in comparison to magnetic resonance imaging as the reference standard. Given the radiation dose and contrast requirement, referring a patient to MDCT only for evaluation of function is not warranted, but rather adds important clinical information to the already acquired data during retrospective triggering for MDCT angiography.
An Overview of Hedgehog Signaling in Fibrosis

The Hedgehog (Hh) signaling pathway plays a key role during embryogenesis and tissue regeneration. Recently, studies revealed that overactivated Hh signaling leads to fibrogenesis in many types of tissues. The activation of Hh signaling is involved in the epithelial-mesenchymal transition and excessive extracellular matrix deposition. Blockade of Hh signaling abolishes the induction of the epithelial-mesenchymal transition and ameliorates tissue fibrosis. Therefore, new therapeutic targets to alleviate fibrosis based on the Hh signaling have attracted a great deal of attention. This is a new strategy for treating fibrosis and other related diseases. In this review, we discuss the crucial role of Hh signaling in fibrogenesis to provide a better understanding of their relationship and to encourage the study of novel targeted therapies.
Dental Fear and Concomitant Factors in 3-6 Year-old Children

Background and aims Dental fear/anxiety as a barrier in accessing oral health care is poorly investigated in Iranian children. The aims of this study were to evaluate the prevalence of dental fear and behavior management problems, as well as to examine the relationship between dental fear/anxiety and probable concomitant factors. Materials and methods Mothers of 200 children aged 3-6 were participated in this descriptive-analytic study, and completed the CFSS-DS, SDQ, Chora and Spielberger questionnaires for both child and parents’ general and dental anxiety in this descriptive- analytic study. Behavior was evaluated according to Frankl scale. Statistical approaches included T-test, chi-sq, and Pearson Linear correlation. Results The mean score of dental fear was 32.15 ± 10 and the prevalence was 22.2%. Significant correlations were found between child’s dental fear, general fear and behavior management problems; however, no relationship was found between child’s dental fear and parental dental or general fear. Conclusion According to results of this study dental fear/anxiety seems to be more conditional and related to child’s temperament than parental impact. Parental evaluation of dental fear can be used as a predictor of child’s dental behavior.
Heparanase mediates cell adhesion independent of its enzymatic activity

Heparanase is an endo‐β‐D‐glucuronidase that cleaves heparan sulfate and is implicated in diverse physiological and pathological processes. In this study we report on a novel direct involvement of heparanase in cell adhesion. We demonstrate that expression of heparanase in nonadherent lymphoma cells induces early stages of cell adhesion, provided that the enzyme is expressed on the cell surface. Heparanasemediated cell adhesion to extracellular matrix (ECM) results in integrin‐dependent cell spreading, tyrosine phosphorylation of paxillin, and reorganization of the actin cytoskeleton. The surface‐bound enzyme also augments cell invasion through a reconstituted basement membrane. Cell adhesion was augmented by cell surface heparanase regardless of whether the cells were transfected with active or point mutated inactive enzyme, indicating that heparanase functions as an adhesion molecule independent of its endoglycosidase activity. The combined feature of heparanase as an ECM‐degrading enzyme and a cell adhesion molecule emphasizes its significance in processes involving cell adhesion, migration, and invasion, including embryonic development, neovascularization, and cancer metastasis. — Goldshmidt, O. , Zcharia, E. , Cohen, M. , Aingorn, H. , Cohen, I. , Nadav, L. , Katz, B. ‐Z. , Geiger, B. , Vlodavsky, I. Heparanase mediates cell adhesion independent of its enzymatic activity. FASEB J. 17, 1015–1025 (2003)
Synergistic and Antagonistic Mutation Responses of Human MCL-5 Cells to Mixtures of Benzo[a]pyrene and 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]pyridine: Dose-Related Variation in the Joint Effects of Common Dietary Carcinogens

Background Chemical carcinogens such as benzo[a]pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) may contribute to the etiology of human diet-associated cancer. Individually, these compounds are genotoxic, but the consequences of exposure to mixtures of these chemicals have not been systematically examined. Objectives We determined the mutagenic response to mixtures of BaP and PhIP at concentrations relevant to human exposure (micromolar to subnanomolar). Methods Human MCL-5 cells (metabolically competent) were exposed to BaP or PhIP individually or in mixtures. Mutagenicity was assessed at the thymidine kinase (TK) locus, CYP1A activity was determined by ethoxyresorufin-O-deethylase (EROD) activity and qRT-PCR, and cell cycle was measured by flow cytometry. Results Mixtures of BaP and PhIP produced dose responses different from those of the individual chemicals; we observed remarkably increased mutant frequency (MF) at lower concentrations of the mixtures (not mutagenic individually), and decreased MF at higher concentrations of the mixtures, than the calculated predicted additive MF of the individual chemicals. EROD activity and CYP1A1 mRNA levels were correlated with TK MF, supporting involvement of the CYP1A family in mutation. Moreover, a cell cycle G2/M phase block was observed at high-dose combinations, consistent with DNA damage sensing and repair. Conclusions Mixtures of these genotoxic chemicals produced mutation responses that differed from those expected for the additive effects of the individual chemicals. The increase in MF for certain combinations of chemicals at low concentrations that were not genotoxic for the individual chemicals, as well as the nonmonotonic dose response, may be important for understanding the mutagenic potential of food and the etiology of diet-associated cancers. Citation David R, Ebbels T, Gooderham N. 2016. Synergistic and antagonistic mutation responses of human MCL-5 cells to mixtures of benzo[a]pyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine: dose-related variation in the joint effects of common dietary carcinogens. Environ Health Perspect 124:88–96; http://dx.doi. org/10.1289/ehp.1409557
The effect of speleothem surface slope on the remanent magnetic inclination

Speleothems are of interest for high‐resolution reconstruction of the Earth's magnetic field. However, little is known about the influence of speleothem morphologies on their natural remanent magnetization (NRM) record. Here we report on a high‐resolution paleomagnetic study of a dome‐shaped speleothem of middle Holocene age from southern Portugal, with special attention to the anisotropy of magnetic susceptibility (AMS) and anisotropy of anhysteretic remanent magnetization (AARM). To assess the potential influence of the slope of the speleothem surface on the recorded remanent magnetization, we compare magnetic directions and AMS and AARM fabrics from subhorizontal to gradually subvertical calcite growth layers collected in a transversal cross section of the speleothem. A linear correlation is observed between magnetic inclinations, calcite laminae slope, and AARM k1 inclination. The AMS fabric is mostly controlled by calcite crystals, with direction of the minimum axes (k3) perpendicular to laminae growth. Magnetic inclinations recorded in inclined and vertical calcite growth layers are underestimated when compared to a global paleosecular variation (PSV) model. After extrapolating magnetic inclinations to the horizontal, the corrected data better fit the PSV model but are still lower than the predicted magnetic inclinations, suggesting that inclination shallowing affects the entire speleothem. We suggest that speleothem morphology exerts a critical role on the magnetic inclination recording, which is controlled by the Earth's magnetic field but also influenced by particle rolling along the sloping surfaces. These observations open new avenues for reconstructing high‐resolution paleomagnetic secular variation records from speleothems and provide new insights into their NRM acquisition mechanisms.