Miracle-dz/UniFAR-FTUs huggingface dataset:
Altered C10 domain in cardiac myosin binding protein-C results in hypertrophic cardiomyopathy.

AIMS A 25-base pair (bp) deletion in the cardiac myosin binding protein-C (cMyBP-C) gene (MYBPC3), proposed to skip exon 33, modifies the C10 domain (cMyBP-CΔC10mut) and is associated with hypertrophic cardiomyopathy (HCM) and heart failure, affecting ∼100 million South Asians. However, the molecular mechanisms underlying the pathogenicity of cMyBP-CΔC10mutin vivo are unknown. We hypothesized that expression of cMyBP-CΔC10mut exerts a poison polypeptide effect leading to improper assembly of cardiac sarcomeres and the development of HCM. METHODS AND RESULTS To determine whether expression of cMyBP-CΔC10mut is sufficient to cause HCM and contractile dysfunction in vivo, we generated transgenic (TG) mice having cardiac-specific protein expression of cMyBP-CΔC10mut at approximately half the level of endogenous cMyBP-C. At 12 weeks of age, significant hypertrophy was observed in TG mice expressing cMyBP-CΔC10mut (heart weight/body weight ratio: 4.43±0.11 mg/g nontransgenic (NTG) vs. 5.34±0.25 mg/g cMyBP-CΔC10mut, P<0.05). Furthermore, hematoxylin and eosin, Masson's trichrome staining, as well as second harmonic generation imaging revealed the presence of significant fibrosis and a greater relative nuclear area in cMyBP-CΔC10mut hearts compared to NTG controls. M-mode echocardiography analysis revealed hypercontractile hearts (EF: 53.4%±2.9% NTG vs. 66.4%±4.7% cMyBP-CΔC10mut; P<0.05) and early diastolic dysfunction (E/E': 28.7±3.7 NTG vs. 46.3±8.4 cMyBP-CΔC10mut; P<0.05), indicating the presence of an HCM phenotype. To assess whether these changes manifested at the myofilament level, contractile function of single skinned cardiomyocytes was measured. Preserved maximum force generation and increased Ca2+-sensitivity of force generation were observed in cardiomyocytes from cMyBP-CΔC10mut mice compared to NTG controls (EC50: 3.6±0.02 µM NTG vs. 2.90±0.01 µM cMyBP-CΔC10mut; P<0.0001). CONCLUSIONS Expression of cMyBP-C protein with a modified C10 domain is sufficient to cause contractile dysfunction and HCM in vivo.
Upregulation of mobility in pancreatic cancer cells by secreted S100A11 through activation of surrounding fibroblasts.

S100A11, a member of S100 family proteins, is actively secreted from pancreatic ductal adenocarcinoma (PDAC) cells. However, the role of the extracellular S100A11 in PDAC progression remains unclear. In the present study, we investigated the extracellular role of S100A11 in cross-talking between PDAC cells and surrounding fibroblasts in PDAC progression.An abundant S100A11 secreted from pancreatic cancer cells stimulated neighboring fibroblasts through receptor for advanced glycation endproducts (RAGE) upon S100A11 binding, and was followed by not only an enhanced cancer cell motility in vitro but also an increased number of the PDAC-derived circulating tumor cells (CTCs) in vivo. Mechanistic investigation of RAGE downstream in fibroblasts revealed a novel contribution of a mitogen-activated protein kinasekinase kinase (MAPKKK), tumor progression locus 2 (TPL2), which is required for positive regulation of PDAC cell motility through induction of cyclooxygenase 2 (COX2) and itscatalyzed production of prostaglandin E2 (PGE2), a strong chemoattractive fatty acid. The extracellularly released PGE2 from fibroblasts was required for the rise in cellular migration as well as infiltration of their adjacent PDAC cells in a co-culture setting. Taken together, our data reveals a novel role of the secretory S100A11 in PDAC disseminative progression through activation of surrounding fibroblasts triggered by the S100A11-RAGE-TPL2-COX2 pathway.These findings of this study will contribute to the establishment of a novel therapeutic antidote toPDACs that are difficult to treat by regulating cancer-associated fibroblasts (CAFs) throughtargeting the identified pathway.
Different prognoses in patients with profound sudden sensorineural hearing loss

Abstract Background: Inner ear hemorrhage is increasingly recognized as a cochlear lesion that can cause profound sudden sensorineural hearing loss (SSNHL). Objectives: To investigate changes of cochlear and vestibular function and to compare therapeutic recovery from profound SSNHL induced by different etiologies. Material and methods: Eighty patients with profound SSNHL (≥90 dB) were divided into an inner ear hemorrhage group and a non-inner ear hemorrhage group by MRI. Statistical analysis was performed to compare the therapeutic effects from vertigo and hearing loss and the outcomes of follow-up in the two groups. Results: There were significant differences between the two groups in terms of the overall 14-day therapeutic response rate (20 vs. 48%), the incidence of imbalance (26.7 vs. 6%), the incidence of semicircular canal dysfunction on the affected side (60 vs. 20%), the incidence of abnormal C-VEMP and O-VEMP on the affected side (63.3 vs. 38%; and 60 vs. 30%, respectively), the average hearing threshold (74.2 ± 10.7 vs. 53.6 ± 11.4 dB), and the word recognition score (65.5 ± 21.7 vs. 83.5 ± 24.5%) at a 12-month follow-up. Conclusions and significance: A higher percentage of patients with profound SSNHL induced by inner ear hemorrhage were associated with vertigo and had a poor prognosis.
A Human Cell Line Model for Interferon-α Driven Dendritic Cell Differentiation

The CD34+ MUTZ-3 acute myeloid leukemia cell line has been used as a dendritic cell (DC) differentiation model. This cell line can be cultured into Langerhans cell (LC) or interstitial DC-like cells using the same cytokine cocktails used for the differentiation of their primary counterparts. Currently, there is an increasing interest in the study and clinical application of DC generated in the presence of IFNα, as these IFNα-DC produce high levels of inflammatory cytokines and have been suggested to be more potent in their ability to cross-present protein antigens, as compared to the more commonly used IL-4-DC. Here, we report on the generation of IFNα-induced MUTZ-DC. We show that IFNα MUTZ-DC morphologically and phenotypically display characteristic DC features and are functionally equivalent to “classic” IL-4 MUTZ-DC. IFNα MUTZ-DC ingest exogenous antigens and can subsequently cross-present HLA class-I restricted epitopes to specific CD8+ T cells. Importantly, mature IFNα MUTZ-DC express CCR7, migrate in response to CCL21, and are capable of priming naïve antigen-specific CD8+ T cells. In conclusion, we show that the MUTZ-3 cell line offers a viable and sustainable model system to study IFNα driven DC development and functionality.
The calcium antagonist drugs

The purpose of this review is to highlight the toxicity of chloral hydrate and to review the management of overdoses with chloral hydrate. Three patients are presented in whom life-threatening cardiac arrhythmias dominated the clinical presentation. These arrhythmias were resistant to standard antiarrhythmic therapy. Also, we have reviewed selected features in eight patients who took overdoses of chloral hydrate who were admitted to an intensive care unit between 1981 and 1988. The pharmacology and toxicology of chloral hydrate are discussed with particular reference to the cardiac arrhythmias that are seen with overdosage. A proposed management scheme is detailed, including intravenously-administered propranolol as the preferred first-line antiarrhythmic agent. A case may be made for the discontinuation of the usage of chloral hydrate. (Med JAust 1988; 149: 686-688) C hlo ra l hydrate was synthesized in 1832, and was introduced as an hypnotic agent by Liebreich in 1869. ' Liebreich reported acute and chronic poisoning and, in 1890, Borntrager penned an article that detailed the first 44 chloral hydraterelated deaths. ' In 1910, Erben labelled chloral hydrate the most dangerous of the hypnotic drugs at a time when heroin and opium were in common use. 1 Chloral hydrate still is used extensively as an hypnotic agent in our community and a mistakenly-held belief exists that it is a safe drug. The incidence of overdose with chloral hydrate is unknown. However, in a survey of consecutive overdoses, Ray et al. showed that chloral hydrate was involved in approximately 1010 of cases that were admitted to a metropolitan teaching-hospital accident and emergency centre, and that most overdoses involved multiple drugs. ' In a five-year review of poisonings in Brisbane, White showed that 62010 of fatalities were a result of therapeutic agents. Notable among these were: chloral hydrate, 10010; narcotic drugs, 14010; barbiturate agents, 13010; and tricyclic drugs, II 010. 3 Ethanol and barbiturates are the most common drugs to be coadministered in overdose; both are capable of potentiating the actions of chloral hydrate. This series and review was prompted by a continued lack of awareness in the medical community of the toxicity of chloral hydrate, and of the appropriate management of an overdose with
Series Solution of Three-Dimensional Unsteady Laminar Viscous Flow Due to a Stretching Surface in a Rotating Fluid

An analytic technique, namely the homotopy analysis method, is applied to solve the Navier-Stokes equations governing unsteady viscous flows due to a suddenly stretching surface in a rotating fluid. Unlike perturbation methods, the current approach does not depend upon any small parameters at all. Besides contrary to all other analytic techniques, it provides us with a simple way to ensure the convergence of solution series. In contrast to perturbation approximations which have about 40% average errors for the considered problem, our series solutions agree well with numerical results in the whole time region 0 ≤ t < +∞. Explicit analytic expressions of the skin friction coefficients are given, which agree well with numerical results in the whole time region 0 ≤ t < +∞. This analytic approach can be applied to solve some complicated three-dimensional unsteady viscous flows governed by the Navier-Stokes equations.
Metaphors in Interactive Visual Analytics

We intuitively understand primary metaphors because they spring from our lived experience as humans. This paper explores the role of primary metaphor in interactive visual analytics. We describe and provide examples of several primary metaphors that can be used in designing and communicating visual representations. We also illustrate how rich and immersive visual analytics environment can support intuitive interaction based around natural metaphors.
Highlights From the Annual Meeting of the American Epilepsy Society 2018

The American Epilepsy Society Meeting in New Orleans attracted more than 5900 attendees. There was a lively exchange of new science, innovation, education, clinical practice, and many other items related to epilepsy. Educational symposia were a major part of the meeting and explored varying topics of interest for all types of epilepsy professionals. This article reviews highlights of the meeting presented in major symposia. Topics ranged from how to treat varying aspects of epilepsy as a consultant in the hospital to finding the scientific underpinning of the interaction between sleep and epilepsy. Pros and cons of novel antiseizure medications, dietary, and stimulation treatments were discussed. Epilepsy may impair memory and we need to learn what is the pathophysiologic relationship. Febrile status epilepticus may have severe consequences for a later life with seizures. Epilepsy professionals should be very well aware of the ethical implications of devasting seizures and their associated disability. These are just a few select topics of the many that we need to study further to archive the final goal to improve the lives of patients with epilepsy.
Progression of heart failure: is protein kinase a hyperphosphorylation of the ryanodine receptor a contributing factor?

The cardiac ryanodine receptor (RyR2)/Ca2+ release channel on the sarcoplasmic reticulum (SR) is regulated by evolutionarily highly conserved signaling pathways that control excitation-contraction (EC) coupling in the heart. Phosphorylation of RyR2 by cAMP-dependent protein kinase (PKA) plays a key role in regulating the channel in response to stress via activation of the sympathetic nervous system (the “fight-or-flight response”). 1 Maladaptive PKA hyperphosphorylation of RyR2 in failing hearts alters channel function, which may cause depletion of SR Ca2+ and diastolic release of SR Ca2+. This can initiate delayed afterdepolarizations that trigger ventricular arrhythmias.1 Mutations in RyR2 recently have been identified in patients with catecholaminergic induced sudden cardiac death (SCD). 2–4⇓⇓ There may be a direct link between the PKA hyperphosphorylation of RyR2 that occurs during the progression of heart failure and fatal cardiac arrhythmias. Regulation of cardiac EC coupling by the release of Ca2+ from the SR via RyR2 in cardiomyocytes, known as Ca2+-induced Ca2+ release (CICR), has been appreciated for more than a decade.5,6⇓ Furthermore, it is well known that the amplitude of the Ca2+ transient generated by SR Ca2+ release determines contractile force in cardiomyocytes. The systems that regulate SR Ca2+ release include: (1) the triggers (predominantly Ca2+ influx through the voltage-gated Ca2+ channel on the plasma membrane); (2) the SR Ca2+ release channel or type 2 RyR2; and (3) the SR Ca2+ reuptake pump (SERCA2a) and its regulator phospholamban. These systems (trigger, release, and reuptake) are modulated by signaling pathways, including the β-adrenergic receptor (β-AR) signaling pathway (ie, phosphorylation by PKA). Activation of the sympathetic nervous system in response to stress results in elevation of cAMP levels and activation of PKA. Phosphorylation of RyR2 may not correlate directly …
Generation of Role Based Access Control Security Policies for Java Collaborative Applications

Java collaborative applications are increasingly and widely used in the form of applets or servlets, as a way to easily download and execute small programs on one's computer. However, security associated with these downloaded applications, even if it exists, is not easily manageable. Most of the time, it relies on the user's ability to define a security policy for his virtual machine, which is undesirable. This paper proposes to integrate an RBAC mechanism for any Java application. It introduces a simple tag process that allows the developer to incorporate the appropriate policy in the source code of his application. The user is endowed with the ability to choose a role that corresponds to the required level of trust required in order for him to embed the policy in the executed code. A case study of a collaborative application shows how works the proposed API for managing roles, generating policies and logging in. At the end, a discussion about the dynamic enforcement of the generated policies is presented.
Research on Urban Leisure Development from the Perspective of Integrated Theory

Urban leisure development (ULD) turns the concept of leisure into economic regionalization, encompassing the leisure ideas of individuals and communities, their leisure behavior, and related industries within the urban scope. The research of ULD is based on our country's state of national development. The importance of ULD is shown to be more important in the forthcoming age of "experience economy. " Hence, the study of ULD will be more highly valued in both theory and practice.
Thyroid status and endothelium-dependent vasodilation in skeletal muscle.

Cardiovascular dysfunction is characteristic of both hypo- and hyperthyroidism. Endothelium-dependent dilation of conductance vessels is impaired in hypothyroidism but augmented in hyperthyroidism. We hypothesized that these alterations in dilation extend into the resistance vasculature of skeletal muscle. To test this hypothesis, rats were made hypothyroid with propylthiouracil (Hypo; n = 13) or hyperthyroid with triiodothyronine (Hyper; n = 9) over 3-4 mo. Compared with euthyroid controls (Eut; n = 14), Hypo rats were characterized by reduced skeletal muscle oxidative capacity and blunted growth; Hyper rats exhibited increased muscle oxidative capacity and left ventricular hypertrophy (P < 0.05 for all effects). Vasodilation to the endothelium-dependent agent acetylcholine ( approximately 2 x 10(-4) M) in skeletal muscle was determined in situ. Conductance in certain muscles increased from control [e.g., soleus: 0.98 +/- 0.15 (Eut), 0.79 +/- 0.14 (Hypo), and 1.06 +/- 0.24 ml.min(-1). 100 g(-1). mmHg(-1) (Hyper); not significant among groups] to acetylcholine [1.91 +/- 0.21 (Eut), 2.28 +/- 0.26 (Hypo), and 2.15 +/- 0.33 ml.min(-1). 100 g(-1). mmHg(-1) (Hyper); P < 0.05 vs. control values for all groups] but did not differ among groups. Expression of mRNA for the endothelial isoform of nitric oxide synthase in resistance vessels isolated from various muscles was similarly unchanged with alterations in thyroid status [e.g., soleus 1A arterioles: 33.15 +/- 0.58 (Eut), 32.73 +/- 0.27 (Hypo), and 32.80 +/- 0.54 (Hyper) cycles at threshold; not significant]. These data suggest that endothelium-dependent dilation of resistance vasculature in skeletal muscle is unchanged in both hypo- and hyperthyroidism. These data also emphasize the importance of examining resistance vasculature to improve understanding of effects of chronic disease on integrated cardiovascular function.
Emotion classification using a CNN_LSTM-based model for smooth emotional synchronization of the humanoid robot REN-XIN

In this paper, we propose an Emotional Trigger System to impart an automatic emotion expression ability within the humanoid robot REN-XIN, in which the Emotional Trigger is an emotion classification model trained from our proposed Word Mover’s Distance(WMD) based algorithm. Due to the long time delay of the WMD-based Emotional Trigger System, we propose an enhanced Emotional Trigger System to enable a smooth interaction with the robot in which the Emotional Trigger is replaced by a conventional convolution neural network and a long short term memory network (CNN_LSTM)-based deep neural network. In our experiments, the CNN_LSTM based model only need 10 milliseconds or less to finish the classification without a decrease in accuracy, while the WMD-based model needed approximately 6-8 seconds to give a result. In this paper, the experiments are conducted based on the same sub-data sets of the Chinese emotional corpus(Ren_CECps) used in former WMD experiments: one comprises 50% data for training and 50% for testing(1v1 experiment), and the other comprises 80% data for training and 20% for testing(4v1 experiment). The experiments are conducted using WMD, CNN_LSTM, CNN and LSTM. The results show that CNN_LSTM obtains the best F1 score (0.35) in the 1v1 experiment and almost the same accuracy of F1 scores (0.366 vs 0.367) achieved by WMD in the 4v1 experiment. Finally, we present demonstration videos with the same scenario to show the performance of robot control driven by CNN_LSTM-based Emotional Trigger System and WMD-based Emotional Trigger System. To improve the comparison, total manual-control performance is also recorded.
Changes in Anticoagulant Utilization Among United States Nursing Home Residents With Atrial Fibrillation From 2011 to 2016

Background Nursing home residents with atrial fibrillation are at high risk for ischemic stroke and bleeding events. The most recent national estimate (2004) indicated less than one third of this high‐risk population was anticoagulated. Whether direct‐acting oral anticoagulant (DOAC) use has disseminated into nursing homes and increased anticoagulant use is unknown. Methods and Results A repeated cross‐sectional design was used to estimate the point prevalence of oral anticoagulant use on July 1 and December 31 of calendar years 2011 to 2016 among Medicare fee‐for‐service beneficiaries with atrial fibrillation residing in long‐stay nursing homes. Nursing home residence was determined using Minimum Data Set 3.0 records. Medicare Part D claims for apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin were identified and point prevalence was estimated by determining if the supply from the most recent dispensing covered each point prevalence date. A Cochran‐Armitage test was performed for linear trend in prevalence. On December 31, 2011, 42.3% of 33 959 residents (median age: 85; Q1 79, Q3 90) were treated with an oral anticoagulant, of whom 8.6% used DOACs. The proportion receiving treatment increased to 47.8% of 37 787 residents as of December 31, 2016 (P<0.01); 48.2% of 18 054 treated residents received DOACs. Demographic and clinical characteristics of residents using DOACs and warfarin were similar in 2016. Half of the 8734 DOAC users received standard dosages and most were treated with apixaban (54.4%) or rivaroxaban (35.8%) in 2016. Conclusions Increases in anticoagulant use among US nursing home residents with atrial fibrillation coincided with declining warfarin use and increasing DOAC use.
Is Gratitude Always Beneficial to Interpersonal Relationships? The Interplay of Grateful Disposition, Grateful Mood, and Grateful Expression Among Married Couples

A growing body of research has documented positive outcomes of gratitude in personal and interpersonal domains. To uncover the dynamic process of gratitude and relational well-being, we examined the interplay of grateful disposition, grateful mood, and grateful expression in ongoing close relationships. Hong Kong Chinese couples (n = 100) participated in a three-wave study across three consecutive weeks. Adopting the Actor–Partner Interdependence Model, we found that at Time 1, grateful disposition not only predicted one’s own grateful mood but also the perceived grateful mood of one’s spouse, both of which predicted marital satisfaction. At Time 2, the couples were randomly assigned to two conditions over 2 weeks: having one spouse keeping a private gratitude journal or overtly expressing gratitude to the other. Couples’ grateful mood increased at Time 3, indicating the effectiveness of both interventions. However, the resulting changes in marital satisfaction differed for the beneficiaries (enactors) and benefactors (targets), such that husbands who perceived their wife’s expressed gratitude as less sincere declined in their marital satisfaction. The results reveal the boundary conditions in evaluating expressions of gratitude and improvement of relationships and provide implications for social exchange and couple therapy.
Improving visual search with image segmentation

People's ability to accurately locate target objects in images is severely affected by the prevalence of the sought objects. This negative effect greatly impacts critical real world tasks, such as baggage screening and cell slide pathology, in which target objects are rare. We present three novel image presentation techniques that are designed to improve visual search. Our techniques rely on the images being broken into image segments, which are then recombined or displayed in novel ways. The techniques and their underlying design reasoning are described in detail, and three experiments are presented that provide initial evidence that these techniques lead to better search performance in a simulated cell slide pathology task.