Miracle-dz/UniFAR-FTUs huggingface dataset:
Relation of the HAS-BLED Bleeding Risk Score to Major Bleeding, Cardiovascular Events, and Mortality in Anticoagulated Patients With Atrial Fibrillation

Background— Stroke risk in atrial fibrillation (AF) using oral vitamin K antagonists is closely related to bleeding risk. The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR [international normalized ratio], elderly, drugs/alcohol concomitantly) bleeding score has demonstrated usefulness in assessing major bleeding risk in patients with AF. However, risk factors for warfarin-associated bleeding also predict stroke risk in patients with AF. We tested the usefulness of the HAS-BLED score for predicting both major bleeding and cardiovascular events in a cohort of anticoagulated patients with AF. Methods and Results— We recruited 965 consecutive anticoagulated outpatients with permanent or paroxysmal AF who were stabilized for at least 6 months on oral anticoagulation (international normalized ratio, 2.0–3.0). Medical history and HAS-BLED score were assessed. Cox regression models were used to determine the association between clinical risk factors and bleeding episodes, adverse cardiovascular events, and mortality. The median HAS-BLED score was 2 (range, 0–6; 29% with a score ≥3 [ie, high risk]). Median follow-up was 861 days (range, 718–1016 days). Independent predictors for major bleeding were age ≥75 years (hazard ratio [HR], 1.74; 95% CI, 1.05–2.87; P=0.030), male sex (HR, 1.70; 95% CI, 1.03–2.80; P=0.036), renal impairment (HR, 2.12; 95% CI, 1.20–3.73; P=0.010), previous bleeding episode (HR, 6.00; 95% CI, 3.73–9.67; P<0.001), current alcohol consumption (HR, 2.28; 95% CI, 1.03–5.06; P=0.043), and concomitant malignant disease (HR, 2.17; 95% CI, 1.13–4.18; P=0.020). Independent predictors for adverse cardiovascular events were age >75 years (HR, 2.20; 95% CI, 1.40–3.46; P=0.001), heart failure (HR, 1.78; 95% CI, 1.20–2.86; P=0.001), and previous stroke (HR, 1.85; 95% CI, 1.20–2.86; P<0.001). The HAS-BLED score was highly predictive for major bleeding events (HR, 2.04; 95% CI, 1.68–2.49; P<0.001) and adverse cardiovascular events (HR, 1.51; 95% CI, 1.27–1.81; P<0.001). The incidence of both bleeding and adverse cardiovascular events was higher as HAS-BLED score increased, and crude bleeding rates only exceeded thrombotic events at a HAS-BLED score >3. The HAS-BLED score also predicted all-cause mortality (HR, 1.68; 95% CI, 1.40–2.01; P<0.001). Conclusions— The HAS-BLED score not only is useful in the assessment of bleeding risk, but also shows some predictive value for cardiovascular events and mortality in anticoagulated patients with AF, consistent with the relationship between thrombosis and bleeding. Nonetheless, the HAS-BLED score has been designed for predicting bleeding risk rather than thrombotic events per se, and specific risk scores for cardiovascular events and mortality should be applied for these events.
Increased Expression of Estrogen Receptor α-36 by Breast Cancer Oncogene IKKε Promotes Growth of ER-Negative Breast Cancer Cells

Background/Aims: The expression of estrogen receptor-α (ERα) is one of the most important diagnostic and prognostic factors of breast cancer. Recently, ERα-36 has been identified as a novel variant of ER-α. ERα-36 lacks intrinsic transcription activity and mainly mediates non-genomic estrogen signaling. The noncanonical IKK family member IKKε is essential for regulating antiviral signaling pathways and is recently discovered as a breast cancer oncogene. IKKε interacts with and phosphorylates ERα on serine 167, induces ERα transactivation activity and enhances ERα binding to DNA in ER-positive breast cancer cells. However, the correlation between IKKε and the ERα-36 signaling pathway in ER-negative breast cancer cells remains unclear. Methods and Results: In this study, we show that IKKε interacts with ERα-36 and increases its expression in breast cancer cells. As shown by western blot assays, the upregulation of ERα-36 by IKKε was significant. In MDA-MB-231 cells which are ER-negative, IKKε was able to increase the expression of ERα-36 in a dose-dependent manner, and the RNA interference assay indicated the correlation between IKKε and ERα-36 expression. Moreover, IKKε enhanced the growth of MDA-MB-231 and MDA-MB-436 cells. Conclusions: These results suggest that IKKε increases ERα-36 expression and is involved in ERα-36 mediated non-genomic estrogen signaling.
C-Reactive Protein-Induced In Vitro Vasorelaxation Is an Artefact Caused by the Presence of Sodium Azide in Commercial Preparations

OBJECTIVE Although C-reactive protein (CRP) is increasingly recognized as an independent risk factor for acute myocardial events, recent evidence suggests that it can directly induce vasorelaxation. This study aimed to investigate the mechanism of this CRP-induced response. METHODS AND RESULTS Isometric tension recordings were used to measure endothelium-dependent and endothelium-independent vascular smooth muscle relaxation in isolated rabbit aortic rings. CRP generated in-house by genetic engineering and expressed in Chinese hamster ovary cells, CRP purified from ascites, and CRP obtained from commercial sources were assessed for vasorelaxing properties. Only the commercial CRP preparation induced vasorelaxation; more than half maximal relaxation was observed at 0.025 microg/mL and maximum relaxation attained at 0.25 microg/mL. Commercial CRP contains high levels of sodium azide, a well-known vasorelaxant. Removal of this agent by dialysis abolished the vasodilatory effect of commercial CRP. Sodium azide alone at concentrations equivalent to that present in the commercial CRP produced a near-identical relaxation pattern to the undialyzed commercial product. CONCLUSIONS CRP has no vasorelaxant properties per se, and the reported vasorelaxant ability of CRP is an artifact caused by sodium azide present in commercial preparations of this agent.
Parallel and distributed computing for data mining

Similar scenarios will occur in other areas: we will see large numbers of radiological images generated in hospitals and immense product and customer databases as the Internet and e-commerce continue to expand.1 Exploring useful information from such data will require efficient parallel algorithms running on high-performance computing systems with powerful parallel I/O capabilities. Without such systems and techniques, invaluable data and information will remain undiscovered. We also need to quantify the time it takes to retrieve pertinent information, for time-critical applications such as credit card fraud detection.2–9 Terms you should know
Constructing Limited Scale-Free Topologies over Peer-to-Peer Networks

Overlay network topology together with peer/data organization and search algorithm are the crucial components of unstructured peer-to-peer (P2P) networks as they directly affect the efficiency of search on such networks. Scale-free (power-law) overlay network topologies are among structures that offer high performance for these networks. A key problem for these topologies is the existence of hubs, nodes with high connectivity. Yet, the peers in a typical unstructured P2P network may not be willing or able to cope with such high connectivity and its associated load. Therefore, some hard cutoffs are often imposed on the number of edges that each peer can have, restricting feasible overlays to limited or truncated scale-free networks. In this paper, we analyze the growth of such limited scale-free networks and propose two different algorithms for constructing perfect scale-free overlay network topologies at each instance of such growth. Our algorithms allow the user to define the desired scale-free exponent ( γ). They also induce low communication overhead when network grows from one size to another. Using extensive simulations, we demonstrate that these algorithms indeed generate perfect scale free networks (at each step of network growth) that provide better search efficiency in various search algorithms than the networks generated by the existing solutions.
Efficacy of a New Low-Dose Oral Contraceptive With Drospirenone in Premenstrual Dysphoric Disorder

Objective: To compare the efficacy of a new low-dose oral contraceptive pill (OCP) formulation with placebo in reducing symptoms of premenstrual dysphoric disorder. Methods: This multicenter, double-blind, randomized clinical trial consisted of 2 run-in and 3 treatment cycles with daily symptom charting; 450 women with symptoms of premenstrual dysphoric disorder were randomized to either placebo or an OCP formulation containing drospirenone 3 mg and ethinyl estradiol 20 &mgr;g. Hormones were administered for 24 days, followed by 4 days of inactive pills (24/4). Results: Scores on the total Daily Record of Severity of Problems decreased by –37.49 in the drospirenone/ethinyl estradiol group and by –29.99 in the placebo group (adjusted mean difference –7.5, 95% confidence interval [CI] –11.2 to –3.8; P < .001 by rank analysis of covariance). Mood symptom scores were reduced by –19.2 and –15.3 in active-treatment and placebo groups, respectively (adjusted mean difference –3.9, 95% CI –5.84 to –2.01; P = .003); physical symptom scores were reduced by –10.7 and –8.6 in active-treatment and placebo groups, respectively (adjusted mean difference –2.1, 95% CI –3.3 to –0.95; P < .001); and behavioral symptom scores were reduced by –7.7 and –6.2 in active-treatment and placebo groups, respectively (adjusted mean difference –1.5, 95% CI –2.251 to –0.727; P < .001). Response, defined as a 50% decrease in daily symptom scores, occurred in 48% of the active-treatment group and 36% of the placebo group (relative risk 1.7, 95% CI 1.1 to 2.6; P = .015) and corresponds to a number-needed-to-treat of 8 patients. Conclusion: A 24/4 regimen of drospirenone 3 mg and ethinyl estradiol 20 &mgr;g improves symptoms associated with premenstrual dysphoric disorder. Level of Evidence: I
Defensins: antifungal lessons from eukaryotes

Over the last years, antimicrobial peptides (AMPs) have been the focus of intense research toward the finding of a viable alternative to current antifungal drugs. Defensins are one of the major families of AMPs and the most represented among all eukaryotic groups, providing an important first line of host defense against pathogenic microorganisms. Several of these cysteine-stabilized peptides present a relevant effect against fungi. Defensins are the AMPs with the broader distribution across all eukaryotic kingdoms, namely, Fungi, Plantae, and Animalia, and were recently shown to have an ancestor in a bacterial organism. As a part of the host defense, defensins act as an important vehicle of information between innate and adaptive immune system and have a role in immunomodulation. This multidimensionality represents a powerful host shield, hard for microorganisms to overcome using single approach resistance strategies. Pathogenic fungi resistance to conventional antimycotic drugs is becoming a major problem. Defensins, as other AMPs, have shown to be an effective alternative to the current antimycotic therapies, demonstrating potential as novel therapeutic agents or drug leads. In this review, we summarize the current knowledge on some eukaryotic defensins with antifungal action. An overview of the main targets in the fungal cell and the mechanism of action of these AMPs (namely, the selectivity for some fungal membrane components) are presented. Additionally, recent works on antifungal defensins structure, activity, and cytotoxicity are also reviewed.
Email conversation network analysis: Work groups and teams in organizations

Email communication is a source of important information, much of which is at first sight hidden. This paper presents an analytical tool that was created to analyze the deeper relationships in the email data. Those include relationships based on an interaction of multiple users in a team. The analytical methods proposed and described in this paper are based on two factors. The first factor is the context, which is a group of multiple users in combination with terms used in the communication. The second factor is the time interval in which the communication was conducted. Based on these factors, we analyze the conversations that take place and get results that are in several different forms presented to the users. The paper presents methods for weighting conversations, users and relationships, as well as methods for finding communities associated with the specified context. Additionally, the concept of the explorative user interface is introduced.
Increased Responsiveness of Peripheral Blood Mononuclear Cells to In Vitro TLR 2, 4 and 7 Ligand Stimulation in Chronic Pain Patients

Glial activation via Toll-like receptor (TLR) signaling has been shown in animals to play an important role in the initiation and establishment of chronic pain. However, our ability to assess this central immune reactivity in clinical pain populations is currently lacking. Peripheral blood mononuclear cells (PBMCs) are an accessible source of TLR expressing cells that may mirror similarities in TLR responsiveness of the central nervous system. The aim of this study was to characterize the IL-1β response to various TLR agonists in isolated PBMCs from chronic pain sufferers (on and not on opioids) and pain-free controls. Venous blood was collected from 11 chronic pain sufferers on opioids (≥ 20 mg of morphine / day), 8 chronic pain sufferers not on opioids and 11 pain-free controls. PBMCs were isolated and stimulated in vitro with a TLR2 (Pam3CSK4), TLR4 (LPS) or TLR7 (imiquimod) agonist. IL-1β released into the supernatant was measured with ELISA. Significantly increased IL-1β expression was found in PBMCs from chronic pain sufferers (on and not on opioids) compared with pain-free controls for TLR2 (F (6, 277) = 15, P<0.0001), TLR4 (F (8, 263) = 3, P = 0.002) and TLR7 (F (2,201) = 5, P = 0.005) agonists. These data demonstrate that PBMCs from chronic pain sufferers were more responsive to TLR agonists compared with controls, suggesting peripheral cells may have the potential to become a source of biomarkers for chronic pain.
Advances on hypoxia inducible factor‐1

DOI: 10.3760/cma.j.issn.0366-6999.20123077 Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100032, China (Wang XJ and Si LB) Correspondence to: WANG Xiao-jun, Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing 100005, China (Tel and Fax: 86-10-69152910. Email: xjwang100@126.com) This study was funded by the National Natural Sciences Foundation of China (No. 81071571). Perspective
Computerization, workplace organization, skilled labour and firm productivity: Evidence for the Swiss business sector

The present study explores empirically the hypothesis that information and communication technologies, new organizational practices and human capital are important determinants of firm efficiency and performance, further that the combined use of these three factors leads to a mutual strengthening of their impact on firm performance. The analytical framework is that of a production function at firm level. The new contribution of this study to the empirical literature is that it is the first empirical study of this type for the Swiss business sector, using a rich data set at firm level for the year 1999 which were collected by means of a postal survey, and giving particular attention to the complementarity issue (several approaches) and to the endogenization of the technology and organization variables.
Measurement of the thickness of the adductor pollicis muscle as a predictor of outcome in critically ill patients.

OBJECTIVE Malnutrition is associated with complications and prolonged hospital stay in critically ill patients. We assessed whether the measurement of the thickness of the adductor pollicis muscle (TAPM), a new tool to assess malnutrition is a valuable prognostic indicator in critically ill patients. METHODS Open cohort study including 248 patients admitted for either medical or surgical intensive care treatment in a tertiary hospital. Two were discharged for having age below 18 years-old and therefore 246 subjects of both sexes completed the entire analysis. Subjective global assessment and APACHE II scores were used to score the patients. TAPM of both hands was measured at admission with a caliper and correlated with mortality, days of mechanical ventilation, and length of hospital stay (LOS). RESULTS There was a significant correlation (R = 0.84, p < 0.001) between TAPM of the right and the left hand. Severe malnourished patients showed TAPM of both the left (12.3 ± 5.5 mm) and right sides (12.9 ± 5.3 mm) significantly lower (p < 0.001) than either patients scored as nourished (right hand = 17.2 ± 5.4 mm and left hand = 15.8 ± 4.6 mm). Risk of death was approximately 8 times higher in patients with APACHEII score above 20 (OR: 8.6, 95% CI: 3.7-20.2; p < 0.001), and approximately 6 times higher in subjects with abnormal TAPM (OR: 6.3, 95% CI: 1.2-32.6; p = 0.02). However, TAPM did not correlate with length of stay and days of mechanical ventilation. CONCLUSION TAPM is a valuable tool to predict mortality in critically ill patients.
The Complexity of the Equivalence Problem for Commutative Semigroups

In this paper, optimal decision procedures for the equivalence, subword, and finite enumeration problems for commutative semigroups are obtained. These procedures require at most space 2^{cn}, where n is the size of the problem instance, and c is some problem independent constant. Furthermore, we show that this space requirement is inevitable: any decision procedure for these problems requires at least exponential space in the worst case, the equivalence, subword, and finite enumeration problems for commutative semigroups are exponential space complete. For the equivalence problem, our results close the gap between the 2^{c'nlog(n)} space upper bound shown by Huynh [Huy85] and the exponential space lower bound resulting from the corresonding bound for the uniform word problem established in [MM82].
Self‐Assembly of Multiple Stacked Nanorings by Vertically Correlated Droplet Epitaxy

Fabrication of advanced artificial nanomaterials is a long‐term pursuit to fulfill the promises of nanomaterials. In the last ten years, Droplet Epitaxy has been emerging as a versatile fabrication method for various complex nanomaterials, but there is a lack of growth protocol to control the growth vertically. Here we report a vertically correlated Droplet Epitaxy growth method. We find that the nanodroplets form preferable on the preexisting nanorings, which enables fabrication of vertically aligned nanostructures by Droplet Epitaxy. Nucleation thermodynamics and growth kinetics have been proposed to explain the vertically correlated Droplet Epitaxy. Heterojunctions can be realized at nanoscale by the presented method. In addition, the nucleation thermodynamics of nanodroplets observed in this article will allow site‐controlled fabrication of nanostructures.
Coupling of a crystal plasticity finite element model with a probabilistic cellular automaton for simulating primary static recrystallization in aluminum

The paper presents a two-dimensional approach for simulating primary static recrystallization, which is based on coupling a viscoplastic crystal plasticity finite-element model with a probabilistic kinetic cellular automaton. The crystal plasticity finite-element model accounts for crystallographic slip and for the rotation of the crystal lattice during plastic deformation. The model uses space and time as independent variables and the crystal orientation and the accumulated slip as dependent variables. The ambiguity in the selection of the active slip systems is avoided by using a viscoplastic formulation that assumes that the slip rate on a slip system is related to the resolved shear stress through a power-law relation. The equations are cast in an updated Lagrangian framework. The model has been implemented as a user subroutine in the commercial finite-element code Abaqus. The cellular automaton uses a switching rule that is formulated as a probabilistic analogue of the linearized symmetric Turnbull kinetic equation for the motion of sharp grain boundaries. The actual decision about a switching event is made using a simple sampling nonMetropolis Monte Carlo step. The automaton uses space and time as independent variables and the crystal orientation and a stored energy measure as dependent variables. The kinetics produced by the switching algorithm are scaled through the mesh size, the grain boundary mobility, and the driving force data. The coupling of the two models is realized by: translating the state variables used in the finite-element plasticity model into state variables used in the cellular automaton; mapping the finite-element integration point locations on the quadratic cellular automaton mesh; using the resulting cell size, maximum driving force, and maximum grain boundary mobility occurring in the region for determining the length scale, time step, and local switching probabilities in the automaton; and identifying an appropriate nucleation criterion. The coupling method is applied to the two-dimensional simulation of texture and microstructure evolution in a heterogeneously deformed, high-purity aluminium polycrystal during static primary recrystallization, considering local grain boundary mobilities and driving forces.
Collaborative information behavior: Exploring collaboration and coordination during information seeking and retrieval activities

Collaborative information behavior is an important and growing area of research in the field of information behavior. Although collaboration is a key component of work in organizational and other settings, most research has primarily focused on individual information behavior and not the collaborative aspects of information behavior. Consequently, there is a pressing need to understand both the conceptual features of this type of behavior and the technical approaches to support these collaborative activities. In this chapter, the authors describe current research in this area and what we are learning about collaboration and coordination during these activities. In particular, the authors present details of ethnographic field studies that are starting to uncover the characteristics of collaborative information behavior. They also discuss a preliminary collaborative information behavior model and some technical explorations that they are conducting in this space.