Miracle-dz/UniFAR-FTUs huggingface dataset:
Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension: A Scientific Statement From the American Heart Association

Venous thromboembolism (VTE) is responsible for the hospitalization of >250 000 Americans annually and represents a significant risk for morbidity and mortality. Despite the publication of evidence-based clinical practice guidelines to aid in the management of VTE in its acute and chronic forms, the clinician is frequently confronted with manifestations of VTE for which data are sparse and optimal management is unclear. In particular, the optimal use of advanced therapies for acute VTE, including thrombolysis and catheter-based therapies, remains uncertain. This report addresses the management of massive and submassive pulmonary embolism (PE), iliofemoral deep vein thrombosis (IFDVT),and chronic thromboembolic pulmonary hypertension (CTEPH). The goal is to provide practical advice to enable the busy clinician to optimize the management of patients with these severe manifestations of VTE. Although this document makes recommendations for management, optimal medical decisions must incorporate other factors, including patient wishes, quality of life, and life expectancy based on age and comorbidities. The appropriateness of these recommendations for a specific patient may vary depending on these factors and will be best judged by the bedside clinician.
Immunomodulator FTY720 Induces eNOS-Dependent Arterial Vasodilatation via the Lysophospholipid Receptor S1P3

The novel immunomodulator FTY720 is effective in experimental models of transplantation and autoimmunity, and is currently undergoing Phase III clinical trials for prevention of kidney graft rejection. FTY720 is a structural analogue of sphingosine-1-phosphate (S1P) and activates several of the S1P receptors. We show that FTY720 induces endothelium-dependent arterial vasodilation in phenylephrine precontracted mouse aortae. Vasodilation did not occur in thoracic aortic rings from eNOS-deficient mice, implicating and effect dependent of activation of the eNOS/NO pathway. Accordingly, FTY720 induced NO release, Akt-dependent eNOS phosphorylation and activation in human endothelial cells. For biological efficacy, FTY720 required endogenous phosphorylation, since addition of the sphingosine kinase antagonist N′,N-dimethylsphingosine (DMS) prevented activation of eNOS in vitro and inhibited vasodilation in isolated arteries. The endothelial phosphorylation of FTY720 was extremely rapid with almost complete conversion after 10 minutes as determined by mass spectrometry. Finally, we identified the lysophospholipid receptor S1P3 as the S1P receptor responsible for arterial vasodilation by FTY720, as the effect was completely abolished in arteries from S1P3-deficient mice. In summary, we have identified FTY720 as the first immunomodulator for prevention of organ graft rejection in clinical development that, in addition, positively affects the endothelium by stimulating NO production, and thus potentially displaying beneficial effects on transplant survival beyond classical T cell immunosuppression.
Probiotic Mechanisms of Action

Probiotics are live microorganisms that provide health benefits to the host when ingested in adequate amounts. The strains most frequently used as probiotics include lactic acid bacteria and bifidobacteria. Probiotics have demonstrated significant potential as therapeutic options for a variety of diseases, but the mechanisms responsible for these effects have not been fully elucidated yet. Several important mechanisms underlying the antagonistic effects of probiotics on various microorganisms include the following: modification of the gut microbiota, competitive adherence to the mucosa and epithelium, strengthening of the gut epithelial barrier and modulation of the immune system to convey an advantage to the host. Accumulating evidence demonstrates that probiotics communicate with the host by pattern recognition receptors, such as toll-like receptors and nucleotide-binding oligomerization domain-containing protein-like receptors, which modulate key signaling pathways, such as nuclear factor-ĸB and mitogen-activated protein kinase, to enhance or suppress activation and influence downstream pathways. This recognition is crucial for eliciting measured antimicrobial responses with minimal inflammatory tissue damage. A clear understanding of these mechanisms will allow for appropriate probiotic strain selection for specific applications and may uncover novel probiotic functions. The goal of this systematic review was to explore probiotic modes of action focusing on how gut microbes influence the host.
Propagating fronts on sandpile surfaces

The flow of granular matter such as sand is often characterized by the motion of a thin superficial layer near the free surface, while the bulk of the solid remains immobile. A pair of equations called the BCRE equations (Bouchaud J-P., Cates M. E., Ravi Prakash J. and Edwards S. F. J. Phys. 4 (1994) 1383) have been proposed to model these flows and account for the dynamic exchange of mass between moving and stationary grains using the simplest kinematic considerations. We uncover a new conservation law for the BCRE equations and its variants that unifies a variety of recent special solutions and show that these equations support simple waves, and are capable of finite time singularities that correspond to propagating erosion fronts.
Cooperative Synchronization in Wireless Networks

Synchronization is a key functionality in wireless networks, enabling a wide variety of services. We consider a Bayesian inference framework whereby network nodes can achieve phase and skew synchronization in a fully distributed way. In particular, under the assumption of Gaussian measurement noise, we derive two message passing methods (belief propagation and mean field), analyze their convergence behavior, and perform a qualitative and quantitative comparison with a number of competing algorithms. We also show that both methods can be applied in networks with and without master nodes. Our performance results are complemented by, and compared with, the relevant Bayesian Cramér-Rao bounds.
Incomparability Results for Classes of Polynomial Tree Series Transformations

Polynomial bottom-up and top-down tree series transducers over partially ordered semirings are considered, and the classes of e-tree-to-tree-series (for short: e-t-ts) and o-tree-to-tree-series (for short: o-t-ts) transformations computed by such transducers are compared. The main result is the following. Let A be a weakly growing semiring and x, y ∈ {deterministic, homomorphism}. The class of o-t-ts transformations computed by x bottom-up tree series transducers over A is incomparable (with respect to set inclusion) with the class of e-t-ts transformations computed by y bottom-up tree series transducers over A. Moreover, the latter class is incomparable with the class of e-t-ts transformations computed by x top-down tree series transducers over A. If additionally A is additively idempotent, then the above statements even hold for every x, y ∈ {polynomial, deterministic, homomorphism}.
Contribution of the coelomic epithelial cells specific to the left testis in the chicken embryo

Background: The left male gonad in the chicken embryo has a thickened cortical layer, but it eventually becomes flattened after the onset of testicular development. Because the destination of the cortical cells migrating from the left gonad remains unclear, we examined this issue herein. Results: The testis‐inducing gene doublesex‐ and mab‐3‐related transcription factor 1 (DMRT1) was detected in a proportion of the columnar and cubic epithelial cells in the cortex of the left testis as well as Sertoli cells in both testes. Interestingly, some of the DMRT1‐expressing cortical cells were contiguous with Sertoli cells in the testis cord. Some cortical cells exhibited a vimentin‐positive cytoplasm that was elongated all the way to the medulla. In addition, a desmosome‐like structure was observed between the elongated cytoplasm in these cells and the adjacent Sertoli cell. After the organ culture, a few cells labeled with a fluorescent dye that stained only the cortical cells at the beginning of the culture were located in the testis cord of the left testis. Conclusions: Some cortical cells expressing DMRT1 were suggested to contribute to the Sertoli cells in the testis cord only after the onset of testicular development and only in the left testis. Developmental Dynamics 246:148–156, 2017. © 2016 Wiley Periodicals, Inc.
Orchestra: intrusion detection using parallel execution and monitoring of program variants in user-space

In a Multi-Variant Execution Environment (MVEE), several slightly different versions of the same program are executed in lockstep. While this is done, a monitor compares the behavior of the versions at certain synchronization points with the aim of detecting discrepancies which may indicate attacks. As we show, the monitor can be implemented entirely in user space, eliminating the need for kernel modifications. As a result, the monitor is not a part of the trusted code base. We have built a fully functioning MVEE, named Orchestra, and evaluated its effectiveness. We obtained benchmark results on a quad-core system, using two variants which grow the stack in opposite directions. The results show that the overall penalty of simultaneous execution and monitoring of two variants on a multi-core system averages about 15% relative to unprotected conventional execution
Effect of Al(OH)3 Addition on the Properties of SiC/Al2O3 Composite Porous Ceramics

SiC/Al2O3 composite porous ceramics were prepared by an in situ reaction bonding technique and sintering in air with SiC and A1(OH)3 as starting materials. The pores in the ceramics were formed by stacking particles of SiC and A12O3. The surface of SiC was oxidized to SiO2 at high temperature. With further increasing the temperature, SiO2 reacted with A12O3 to form mullite. The reaction bonding characteristics, phase composition, and mechanical strength as well as microstructure of porous SiC ceramics were investigated.
Poor man's TBR: a simple model reduction scheme

This paper presents a model reduction algorithm motivated by a connection between frequency domain projection methods and approximation of truncated balanced realizations. The method produces guaranteed passive models, has near-optimal error properties, is computationally simple to implement, contains error estimators, and can incorporate frequency weighting information in a straightforward manner. Examples are shown to prove that the method can outperform the standard order reduction techniques by providing similar accuracy with lower models or superior accuracy for the same size model.
Buthionine Sulfoximine and Myeloablative Concentrations of Melphalan Overcome Resistance in a Melphalan-Resistant Neuroblastoma Cell Line

Background Alkylator resistance contributes to treatment failure in high-risk neuroblastoma. Buthionine sulfoximine (BSO) can deplete glutathione and synergistically enhance in vitro sensitivity to the alkylating agent melphalan (L-PAM) for many neuroblastoma cell lines, but optimal use of this combination needs to be defined because clinical responses have been less frequent and not durable. Patients and Methods The authors established and characterized a neuroblastoma cell line (CHLA-171) from a patient who died of progressive disease after treatment with BSO and low-dose L-PAM. Results CHLA-171 lacks MYCN amplification, expresses PGP (P-glycoprotein) 9.5 RNA, and shows cell surface antigen expression (human leukocyte antigen class I weakly positive, but HSAN 1.2 (hybridoma, SAN 1.2) and anti-GD2 (anti-ganglioside GD2 antibody) strongly positive) characteristic of neuroblastoma cell lines. Twenty-four hours of BSO treatment (0–1,000 &mgr;mol/L) maximally depleted CHLA-171 glutathione to 36% of baseline. The cytotoxic response of CHLA-171 to BSO and L-PAM, alone and in combination, was measured by digital image microscopy (DIMSCAN) over a range of drug concentrations and compared with drug levels obtained in the patient during BSO/L-PAM therapy. As single agents, CHLA-171 was highly resistant to L-PAM (LD 90 = 42 &mgr;mol/L; peak plasma concentration in the patient equals 3.9 &mgr;mol/L) and moderately resistant to BSO (LD 90 = 509 &mgr;mol/L; steady-state concentration in the patient equals 397 &mgr;mol/L). Treatment with a 10:1 (BSO:L-PAM) fixed ratio combination synergistically overcame resistance (3–4 logs of cell kill, combination index <1) at clinically achievable levels of BSO (100–400 &mgr;mol/L) and levels of L-PAM (10–40 &mgr;mol/L) clinically achievable only with hematopoietic stem cell support. Conclusions The in vitro results obtained for CHLA-171 suggest that BSO/L-PAM therapy may be optimally effective for drug-resistant neuroblastoma using myeloablative doses of L-PAM.
Gazemarks: gaze-based visual placeholders to ease attention switching

Many tasks require attention switching. For example, searching for information on one sheet of paper and then entering this information onto another one. With paper we see that people use fingers or objects as placeholders. Using these simple aids, the process of switching attention between displays can be simplified and speeded up. With large or multiple visual displays we have many tasks where both attention areas are on the screen and where using a finger as a placeholder is not suitable. One way users deal with this is to use the mouse and highlight their current focus. However, this also has its limitations -- in particular in environments where there is no pointing device. Our approach is to utilize the user's gaze position to provide a visual placeholder. The last area where a user fixated on the screen (before moving their attention away) is highlighted; we call this visual reminder a Gazemark. Gazemarks ease orientation and the resumption of the interrupted task when coming back to this display. In this paper we report on a study where the effectiveness of using Gazemarks was investigated, in particular we show how they can ease attention switching. Our results show faster completion times for a resumed simple visual search task when using this technique. The paper analyzes relevant parameters for the implementation of Gazemarks and discusses some further application areas for this approach.
Ethical Issues in Brain–Computer Interface Research, Development, and Dissemination

The steadily growing field of brain–computer interfacing (BCI) may develop useful technologies, with a potential impact not only on individuals, but also on society as a whole. At the same time, the development of BCI presents significant ethical and legal challenges. In a workshop during the 4th International BCI meeting (Asilomar, California, 2010), six panel members from various BCI laboratories and companies set out to identify and disentangle ethical issues related to BCI use in four case scenarios, which were inspired by current experiences in BCI laboratories. Results of the discussion are reported in this article, touching on topics such as the representation of persons with communication impairments, dealing with technological complexity and moral responsibility in multidisciplinary teams, and managing expectations, ranging from an individual user to the general public. Furthermore, we illustrate that where treatment and research interests conflict, ethical concerns arise. On the basis of the four case scenarios, we discuss salient, practical ethical issues that may confront any member of a typical multidisciplinary BCI team. We encourage the BCI and rehabilitation communities to engage in a dialogue, and to further identify and address pressing ethical issues as they occur in the practice of BCI research and its commercial applications.
Dynamic Carpooling in Urban Areas: Design and Experimentation with a Multi-Objective Route Matching Algorith

This paper focuses on dynamic carpooling services in urban areas to address the needs of mobility in real-time by proposing a two-fold contribution: a solution with novel features with respect to the current state-of-the-art, which is named CLACSOON and is available on the market; the analysis of the carpooling services performance in the urban area of the city of Cagliari through emulations. Two new features characterize the proposed solution: partial ridesharing, according to which the riders can walk to reach the driver along his/her route when driving to the destination; the possibility to share the ride when the driver has already started the ride by modelling the mobility to reach the driver destination. To analyse which features of the population bring better performance to changing the characteristics of the users, we also conducted emulations. When compared with current solutions, CLACSOON allows for achieving a decrease in the waiting time of around 55% and an increase in the driver and passenger success rates of around 4% and 10%,respectively. Additionally, the proposed features allowed for having an increase in the reduction of the CO2 emission by more than 10% with respect to the traditional carpooling service.
A Computational Framework for Lexical Description

To achieve generality, natural language parsers require dictionaries which handle lexical information in a linguistically motivated but computationally viable manner. Various rule formalisms are presented which process orthographic effects, word structure, and lexicai redundancy in a manner which allows the statement of linguistic generalisations with a clear computational interpretation. A compact description of a medium-sized subset of the English lexicon can be stated using these formalisms. The proposed mechanisms have been implemented and tested, but require to be refined further if they are to be regarded as an interesting linguistic theory.
Treatment Interruptus: The Need for Withdrawal

TO THE EDITOR: We read with great interest a randomized controlled trial by Sotoudehmanesh et al. (1) titled “Indomethacin May Reduce the Incidence and Severity of Acute Pancreatitis After ERCP” that has been published in the recent issue of the Journal. The authors concluded that rectal indomethacin given right before endoscopic retrograde cholangiopancreatography (ERCP) can reduce the incidence and severity of post-ERCP pancreatitis (PEP). However, before incorporating this inexpensive, easily available nonsteroidal anti-inflammatory drug (NSAID) into our clinical practice for PEP prevention, several issues need further clarification: (a) It had been pointed out from a prospective large sample study that only individuals with serum amylase levels fivefold the normal upper limits and persistent pancreaticlike pain for 24 h after ERCP strongly suggest possibility of PEP (2); however, the authors stated that besides the 2-h measurement, serum amylase was repeated the next morning, and it is not clear what the exact time interval was. This may cast some doubt on the accuracy of the diagnosis of PEP in this study. (b) In the Methods section, the authors claimed subgroup analysis was used to evaluate the effect of indomethacin related to different variables. Notwithstanding, due to the lack of relevant information, it is not clear whether these subgroup analyses were ad hoc or post hoc. If these subgroup analyses were performed retrospectively, it should be considered as “fishing” for positive results, and the results from subgroup analyses should be treated with caution (3). (c) No explanation was provided as to why none of the sphincter of Oddi dysfunction (SOD) patients developed PEP, which is contrary to most other reported trials, with PEP incidence of up to 24% for patients with suspicious SOD (4). (d) They found that pancreatic duct injection, pancreatic duct cannulation more than once, and age less than 60 yr were significant risk factors for developing PEP. Certainly, it is convenient to perform a univariate analysis for exploration of each variable’s influence on the primary outcome; nonetheless, up to now, available evidence suggests that the incidence of PEP was not determined by any single factor. Thus, a multivariate statistical analysis with logistic regression allowing estimation of the influence of covariates on the incidence of PEP seems more appropriate. To summarize, this study suggests indomethacin may be an attractive pharmacotherapy for the prevention of PEP because it is inexpensive, universally available, and relatively safe. Clarification on some raised concerns will better our understanding of the mystery of PEP and its pharmacotherapy prevention. Yu Bai, M.D. Duowu Zou, M.D. Zhaoshen Li, M.D.
Intra-Organizational Integration and Innovation: Organizational Structure, Environmental Contingency and R&D Performance

It is widely thought that intra-firm integration has a positive effect on organizational performance, especially in environments characterized by complex and uncertain information. However, counter arguments suggest that integration may limit flexibility and thereby reduce performance in the face of uncertainty. Research and development activities of a firm are especially likely to face complex and uncertain information environments. Following prior work in contingency theory, this paper analyzes the effects of intra-organizational integration on manufacturing firms’ innovative performance. Based on a survey of R&D units in US manufacturing firms and patent data from the NBER patent database, we examine the relation between mechanisms for linking R&D to other units of the firm and the relative innovativeness of the firm. Furthermore, we argue that the impact of integration may vary by the importance of secrecy in protecting firms’ innovation advantages. We find that intra-firm integration is associated with higher self-reported innovativeness and more patents. We also find some evidence that this effect is moderated by the appropriability regime the firm faces, with the benefits of cross-functional integration being weaker in industries where secrecy is especially important. These results both support and develop the contingency model of organizational performance.
A Qualitative Study of Determinants of PTSD Treatment Initiation in Veterans

Although there are effective treatments for Posttraumatic Stress Disorder (PTSD), many PTSD sufferers wait years to decades before seeking professional help, if they seek it at all. An understanding of factors affecting treatment initiation for PTSD can inform strategies to promote help-seeking. We conducted a qualitative study to identify determinants of PTSD treatment initiation among 44 U.S. military veterans from the Vietnam and Afghanistan/Iraq wars; half were and half were not receiving treatment. Participants described barriers to and facilitators of treatment initiation within themselves, the post-trauma socio-cultural environment, the health care and disability systems, and their social networks. Lack of knowledge about PTSD was a barrier that occurred at both the societal and individual levels. Another important barrier theme was the enduring effect of experiencing an invalidating socio-cultural environment following trauma exposure. In some cases, system and social network facilitation led to treatment initiation despite individual-level barriers, such as beliefs and values that conflicted with help-seeking. Our findings expand the dominant model of service utilization by explicit incorporation of factors outside the individual into a conceptual framework of PTSD treatment initiation. Finally, we offer suggestions regarding the direction of future research and the development of interventions to promote timely help-seeking for PTSD.