Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid Heart Rate Increase at Onset of Exercise Predicts Adverse Cardiac Events in Patients With Coronary Artery Disease

Background—We previously demonstrated that reduced vagal activity and/or increased sympathetic activity identify post–myocardial infarction patients at high risk for cardiac mortality. Simple and inexpensive autonomic markers are necessary to perform autonomic screening in large populations. We tested our hypothesis that abnormally elevated heart rate (HR) responses at the onset of an exercise stress test, which imply rapid vagal withdrawal immediately preceding sympathetic activation, might predict adverse cardiac events in patients with documented coronary artery disease. Methods and Results—The HR increase during the first minute (&Dgr;HR1 minute) of a symptom-limited exercise stress test was quantified in 458 patients with documented coronary artery disease. During a 6-year (interquartile range 3.7 to 9.0 years) follow-up, 71 patients experienced adverse cardiac events (21 cardiac deaths, 56 nonfatal myocardial infarctions). In univariate analysis, &Dgr;HR1 minute ≥12 bpm (above the median value of its distribution) predicted both adverse outcome and cardiac death with a hazard ratio of 5.0 (95% CI 2.7 to 9.1; P<0.0001) and of 15.6 (95% CI 2.0 to 118.7; P<0.001), respectively. After adjustment for potential confounders, &Dgr;HR1 minute remained predictive for both combined end points and for cardiac death. Conclusions—A marked HR increase at the onset of a standard exercise stress test is a novel and easily available parameter that could be clinically useful as an independent predictor of adverse cardiac events, including death, among patients with documented coronary artery disease.
A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure.

BACKGROUND Acute renal failure (ARF) requiring dialysis in critically ill patients is associated with an in-hospital mortality rate of 50 to 80%. The worldwide standard for renal replacement therapy is intermittent hemodialysis (IHD). Continuous hemodialysis and hemofiltration techniques have recently emerged as alternative modalities. These two therapies have not been directly compared. METHODS A multicenter, randomized, controlled trial was conducted comparing two dialysis modalities (IHD vs. continuous hemodiafiltration) for the treatment of ARF in the intensive care unit (ICU). One hundred sixty-six patients were randomized. Principal outcome measures were ICU and hospital mortality, length of stay, and recovery of renal function. RESULTS Using intention-to-treat analysis, the overall ICU and in-hospital mortalities were 50.6 and 56.6%, respectively. Continuous therapy was associated with an increase in ICU (59.5 vs. 41.5%, P < 0.02) and in-hospital (65.5 vs. 47.6%, P < 0.02) mortality relative to intermittent dialysis. Median ICU length of stay from the time of nephrology consultation was 16.5 days, and complete recovery of renal function was observed in 34.9% of patients, with no significant group differences. Despite randomization, there were significant differences between the groups in several covariates independently associated with mortality, including gender, hepatic failure, APACHE II and III scores, and the number of failed organ systems, in each instance biased in favor of the intermittent dialysis group. Using logistic regression to adjust for the imbalances in group assignment, the odds of death associated with continuous therapy was 1.3 (95% CI, 0.6 to 2.7, P = NS). A detailed investigation of the randomization process failed to explain the marked differences in patient assignment. CONCLUSIONS A randomized controlled trial of alternative dialysis modalities in ARF is feasible. Despite the potential advantages of continuous techniques, this study provides no evidence of a survival benefit of continuous hemodiafiltration compared with IHD. This study did not control for other major clinical decisions or other supportive management strategies that are widely variable (for example, nutrition support, hemodynamic support, timing of initiation, and dose of dialysis) and might materially influence outcomes in ARF. Standardization of several aspects of care or extremely large sample sizes will be required to answer optimally the questions originally posed by this investigation.
The organization of RNA contacts by PTB for regulation of FAS splicing

Post-transcriptional steps of gene expression are regulated by RNA binding proteins. Major progress has been made in characterizing RNA-protein interactions, from high resolution structures to transcriptome-wide profiling. Due to the inherent technical challenges, less attention has been paid to the way in which proteins with multiple RNA binding domains engage with target RNAs. We have investigated how the four RNA recognition motif (RRM) domains of Polypyrimidine tract binding (PTB) protein, a major splicing regulator, interact with FAS pre-mRNA under conditions in which PTB represses FAS exon 6 splicing. A combination of tethered hydroxyl radical probing, targeted inactivation of individual RRMs and single molecule analyses revealed an unequal division of labour between the four RRMs of PTB. RNA binding by RRM4 is the most important for function despite the low intrinsic binding specificity and the complete lack of effect of disrupting individual RRM4 contact points on the RNA. The ordered RRM3-4 di-domain packing provides an extended binding surface for RNA interacting at RRM4, via basic residues in the preceding linker. Our results illustrate how multiple alternative low-specificity binding configurations of RRM4 are consistent with repressor function as long as the overall ribonucleoprotein architecture provided by appropriate di-domain packing is maintained.
THERAPEUTIC PROGRESS‐REVIEW XXXV ASPIRIN IN THE NEXT DECADE

Clinical trials of salicylates date back to the Eighteenth century. This compound is naturally present in the bark of willow (botanical name, Salicaceae) and the Reverend Edward Stone applied the prevailing philosophy of his time to their study: that is, that remedies for diseases would be found close to their causes. He noted that winter colds and rheumatic pains occur in damp climates, just the natural habitat of the willow. In his open, uncontrolled trial he treated 50 patients with ‘ague’ and each received 20 grains of powdered willow bark every 4 h. He reported excellent results. Following these early observations aspirin (acetylsalicylic acid) became established as the best known simple analgesic. Subsequently its antipyretic and anti-inflammatory properties lead to its use in the management of many febrile illnesses and most rheumatic disorders. Its role in the management of these problems is undisputed. However, when it was shown that aspirin might have a useful therapeutic effect on platelets and might thereby have a role in the prevention and management of vascular disease, the situation was less clear. Early studies in patients with coronary artery or cerebrovascular diseases suggested that aspirin might have a useful effect but failed to prove this convincingly. We have recently seen the publication of six major trials concerning the use of aspirin in both cardioand cerebrovascular disease. These have important therapeutic implications and it is an appropriate time to assess the new data critically and review its application to clinical practice.
Neuronal Plasticity and Signal Transduction in Nociceptive Neurons: Implications for the Initiation and Maintenance of Pathological Pain

Pathological pain, consisting of tissue injury-induced inflammatory and nerve injury-induced neuropathic pain, is an expression of neuronal plasticity. One component of this is that the afferent input generated by injury and intense noxious stimuli triggers an increased excitability of nociceptive neurons in the spinal cord. This central sensitization is an activity-dependent functional plasticity that results from activation of different intracellular kinase cascades leading to the phosphorylation of key membrane receptors and channels, increasing synaptic efficacy. Central sensitization is both induced and maintained in a transcription-independent manner. Several different intracellular signal transduction cascades converge on MAPK (mitogen-activated protein kinase), activation of which appears to be a master switch or gate for the regulation of central sensitization. In addition to posttranslational regulation, the MAPK pathway may also regulate long-term pain hypersensitivity, via transcriptional regulation of key gene products. Pharmacological intervention targeted specifically at the signal transduction pathways in nociceptive neurons may provide, therefore, new therapeutic opportunities for pathological pain.
Comparison of Gene Expression in Human Embryonic Stem Cells, hESC-Derived Mesenchymal Stem Cells and Human Mesenchymal Stem Cells

We present a strategy to identify developmental/differentiation and plasma membrane marker genes of the most primitive human Mesenchymal Stem Cells (hMSCs). Using sensitive and quantitative TaqMan Low Density Arrays (TLDA) methodology, we compared the expression of 381 genes in human Embryonic Stem Cells (hESCs), hESC-derived MSCs (hES-MSCs), and hMSCs. Analysis of differentiation genes indicated that hES-MSCs express the sarcomeric muscle lineage in addition to the classical mesenchymal lineages, suggesting they are more primitive than hMSCs. Transcript analysis of membrane antigens suggests that IL1R1low, BMPR1Blow, FLT4low, LRRC32low, and CD34 may be good candidates for the detection and isolation of the most primitive hMSCs. The expression in hMSCs of cytokine genes, such as IL6, IL8, or FLT3LG, without expression of the corresponding receptor, suggests a role for these cytokines in the paracrine control of stem cell niches. Our database may be shared with other laboratories in order to explore the considerable clinical potential of hES-MSCs, which appear to represent an intermediate developmental stage between hESCs and hMSCs.
Phyllosilicates and sulfates at Endeavour Crater, Meridiani Planum, Mars

Phyllosilicates have been identified on the Martian surface from orbit, and are hypothesized to have formed under wet, non‐acidic conditions early in the planet's history. Exposures of these minerals have not yet been examined by a landed mission. Using Mars Reconnaissance Orbiter data, we report the detection of phyllosilicate‐bearing outcrops that may be accessible by the Mars Exploration Rover Opportunity currently exploring Meridiani Planum. The phyllosilicates are associated with layered, polygonally fractured rocks exposed in the rim of the 20 km diameter crater Endeavour. These rocks may have formed via regional or global‐scale processes of aqueous alteration that predated the period of acid sulfate formation recorded in the rocks that Opportunity has studied to date. Detailed characterization by Opportunity could better constrain the conditions under which these phyllosilicates formed. Hydrated sulfates are also detected from orbit in the plains adjacent to Endeavour's rim, providing the first opportunity for ground truth of these detections.
Dissemination of management into politics: Michael Porter and the political uses of management consulting

The article contributes to the literature on management dissemination by looking at how management fashions are diffused into and circulated in politics. The ideas of management have been increasingly disseminated into the realm of politics during recent decades. To illustrate how this takes place, this article examines the spread of Michael Porter’s ideas on national politics. Porter’s work is considered a management fashion that has been skilfully packaged; a new form of the 20th-century tradition of state-led social engineering which takes the form of management fashion-style packaging. For this he is seen as a global guru in national politics, and this development is regarded as a new form of consultocracy in the realm of democracies. In consultocracy, the ideas of management consulting are often adopted into politics as a common justifying rationality of power for the political elites. Thus we call for further research on the underlying dynamics of the power involved as management fashions are disseminated into the realm of politics.
Speculation and Negation: Rules, Rankers, and the Role of Syntax

This article explores a combination of deep and shallow approaches to the problem of resolving the scope of speculation and negation within a sentence, specifically in the domain of biomedical research literature. The first part of the article focuses on speculation. After first showing how speculation cues can be accurately identified using a very simple classifier informed only by local lexical context, we go on to explore two different syntactic approaches to resolving the in-sentence scopes of these cues. Whereas one uses manually crafted rules operating over dependency structures, the other automatically learns a discriminative ranking function over nodes in constituent trees. We provide an in-depth error analysis and discussion of various linguistic properties characterizing the problem, and show that although both approaches perform well in isolation, even better results can be obtained by combining them, yielding the best published results to date on the CoNLL-2010 Shared Task data. The last part of the article describes how our speculation system is ported to also resolve the scope of negation. With only modest modifications to the initial design, the system obtains state-of-the-art results on this task also.
Three's company: understanding communication channels in three-way distributed collaboration

We explore the design of a system for three-way collaboration over a shared visual workspace, specifically in how to support three channels of communication: person, reference, and task-space. In two studies, we explore the implications of extending designs intended for dyadic collaboration to three-person groups, and the role of each communication channel. Our studies illustrate the utility of multiple configurations of users around a distributed workspace, and explore the subtleties of traditional notions of identity, awareness, spatial metaphor, and corporeal embodiments as they relate to three-way collaboration.
Molecular Connections between Cancer Cell Metabolism and the Tumor Microenvironment

Cancer cells preferentially utilize glycolysis, instead of oxidative phosphorylation, for metabolism even in the presence of oxygen. This phenomenon of aerobic glycolysis, referred to as the “Warburg effect”, commonly exists in a variety of tumors. Recent studies further demonstrate that both genetic factors such as oncogenes and tumor suppressors and microenvironmental factors such as spatial hypoxia and acidosis can regulate the glycolytic metabolism of cancer cells. Reciprocally, altered cancer cell metabolism can modulate the tumor microenvironment which plays important roles in cancer cell somatic evolution, metastasis, and therapeutic response. In this article, we review the progression of current understandings on the molecular interaction between cancer cell metabolism and the tumor microenvironment. In addition, we discuss the implications of these interactions in cancer therapy and chemoprevention.
Ring Around the Roses

A 47-year-old woman presents with an ulcerated perineal lesion. The patient has a history of a biopsy-proven mucinous adenocarcinoma of the rectum that infiltrated the posterior vaginal wall (cT4). After radiotherapy the tumor was staged as ypT4pN0cM0 with only few remaining viable malignant cells (tumor regression grade 3). Although the original tumor was completely resected, based on the worrisome physical findings, the perineal lesion was excised. Histologic examination shows extensive white fat necrosis underlying granulation tissue. There is no evidence of malignancy, and cytokeratin and CDX-2 imunohistochemistry is negative (not shown). The necrotic fat is in stage of resorption in which numerous foamy histiocytes (Figure 1A), highlighted by the histiocytic marker CD68 (Figure 1B), surround the cytoplasmic outlines of necrotic adipocytes. These macrophages contain numerous clear cytoplasmic vacuoles filled with lipid (“lipophages”). This particular encircling arrangement of histiocytes is a frequent finding in white fat necrosis regardless of etiology. In contrast to a nonselective response to injury, as manifest by granulation tissue, the absence of a typical neutrophilic or lymphoplasmacellular infiltrate suggests a specific type of response to fat necrosis. It is possible the necrosis of the white fat results in the release of paracrine signals with selective migration of monocytes; however, we are unaware of an established pathophysiologic explanation for this type of cellular response to injury. Irrespective of the underlying pathophysiology, the recognition of this architectural arrangement of histiocytes can be very helpful, especially when histiocytes do not demonstrate the typical foamy cytoplasm. Given its remarkable resemblance to children holding hands and dancing around in a circle while singing, we find the name “ring around the roses” particularly suitable for this pattern. The name of this popular nursery rhyme can be traced back to 1790, and the first printed version appeared in 1881. Even though this rhyme remains popular in modern culture, the exact meaning of the wording “Ring around the rosey, A pocketful of posies. Ashes, ashes. We Figure 1. (A) Hematoxylin and eosin stained section demonstrates histiocytes with foamy cytoplasm encircling the necrotic outlines of the underlying fat necrosis. (B) Immunohistochemistry for the monocyte/macrophage marker CD68 demonstrates foamy histiocytes in a ring-like configuration. Scale bars = 50 mm
Designing prevention programmes to reduce incidence of dementia: prospective cohort study of modifiable risk factors

Objective To estimate the percentage reduction in incidence of dementia that would be obtained if specific risk factors were eliminated. Design Prospective seven year cohort study. Setting General population, Montpellier, France. Participants 1433 people aged over 65 with a mean baseline age of 72.5 (SD 5.1) years. Main outcome measures Diagnosis of mild cognitive impairment or dementia established by a standardised neurological examination. Results Cox models were constructed to derive hazard ratios and determine confounding and interaction effects for potentially modifiable risk factors for dementia. Mean percentage population attributable fractions were calculated with 95% confidence intervals derived from bootstrapping for seven year incidence of mild cognitive impairment or dementia. The final model retained crystallised intelligence (population attributable fraction 18.11%, 95% confidence interval 10.91% to 25.42%), depression (10.31%, 3.66% to 17.17%), fruit and vegetable consumption (6.46%, 0.15% to 13.06%), diabetes (4.88%, 1.87% to 7.98%), and apolipoprotein E ε4 allele (7.11%, 2.44% to 11.98%). Conclusions Increasing crystallised intelligence and fruit and vegetable consumption and eliminating depression and diabetes are likely to have the biggest impact on reducing the incidence of dementia, outweighing even the effect of removing the principal known genetic risk factor. Although causal relations cannot be concluded with certainty, the study suggests priorities that may inform public health programmes.
Nouvelle méthode d'estimation des différences de temps d'arrivée pour la localisation des objets connectés haut débit

La vision future de l'internet des objets (IdO) et Internet du Tout (OIE) plongera les personnes soi-disant environnements intelligents impliquant un grand nombre de secteurs d'applications telles que l'habitat intelligent, smart-villes, surveillance de l'environnement, l'e-sante . IdO et l'OIE ont tendance a faire des objets du quotidien lisible, identifiable, localisable, adressable et controlable via le deploiement sans fil generalisee et l'Internet. Parmi ces capacites, la localisation et plus largement le positionnement omnipresente joueront, dans un proche avenir, un role cle pour promouvoir une autre vision emergente: un Internet spatio-temporelle des lieux (IoP), qui serait en mesure de structurer et d'organiser, par des moyens des approches sans fil d'energie savez, le contenu spatial d'Internet. Il est bien connu que dans les reseaux locaux sans fil et personnelles, l'encombrement du spectre, les communications a faible efficacite energetique et l'exploitation insuffisante des ressources spatiales sont parmi les facteurs qui peuvent ralentir son developpement en termes de debit et de l'autonomie. Pour surmonter ces restrictions inevitables, la technologie de localisation sans fil, comme le mecanisme pour decouvrir relation spatio-temporelle entre les objets connectes, apparait ici aussi comme une des solutions cles. Ce est parce que les techniques de localisation dedies a la communication sans fil peuvent aider a developper plus largement l'exploitation des ressources spatiales et de permettre la conduite routage optimise pour une faible energie communication multi-hop et la decongestion du spectre pour Green ICT (Information et Communication Technology). Pour proposer des systemes optimises atteindre a la fois la communication des taux de donnees eleves et la localisation precise, nous definissons un TDOA bien adapte (Time Difference of Arrival) methode basee en mesure d'effectuer la localisation basee sur des signaux de communication et de donnees seulement. Avec cette technique, contrairement estimations TDOA classiques, il est possible de diminuer considerablement la complexite des infrastructures necessaires en utilisant des configurations SIMO (Single Input Multiple Output), MISO (Multiple Input Single Output) ou MIMO (Multiple Input Multiple Output) dans les objets connectes . Toute cette etude est faite dans le cadre de l'IEEE 802.11ad specifications de l'alliance standard et WiGig, mais les solutions proposees sont compatibles avec d'autres normes et peuvent etre etendues a d'autres applications de contexte courant necessitant entrees de localisation tels que la robotique par exemple ou de shopping intelligent.
Von Frauenbewegungen zu Frauenorganisationen, von Empowerment zu FrauenMenschenrechten. Über das Globalwerden internationaler Frauenbewegungspolitik

Internationale Frauenbewegungspolitik entwickelt sich zu einer dezidiert globalen Politik. Den Kern dieses Globalwerdens bilden zwei parallele, sich zum Teil gegenseitig verstarkende Prozesse: die Vernetzung und NGOisierung von Frauenbewegungen weltweit und die inhaltliche Akzentuierung des Ansatzes der FrauenMenschenrechte. Beide Veranderungstendenzen sind politisch ambivalent. Einerseits unterstutzen sie die Verhandlungspositionen von Frauenbewegungsakteurinnen in den Szenarien globaler Politik, andererseits gefahrden sie die besonderen, basisbezogenen Potenziale von Frauenbewegungspolitik. Gleichwohl sind die frauenpolitischen Chancen dieses Prozesses vor allem deshalb beachtlich, weil darin verschiedenste frauenpolitische Handlungsstrategien auf allen politischen Handlungsebenen verschrankt und integriert werden konnen.