Miracle-dz/UniFAR-FTUs huggingface dataset:
Variation in Hospital Use and Outcomes Associated With Pulmonary Artery Catheterization in Heart Failure in the United States

Background—There has been an increase in the use of pulmonary artery (PA) catheters in heart failure (HF) in the United States in recent years. However, patterns of hospital use and trends in patient outcomes are not known. Methods and Results—In the National Inpatient Sample 2001 to 2012, using International Classification of Diseases-Ninth Revision codes, we identified 11 888 525 adult (≥18 years) HF hospitalizations nationally, of which an estimated 75 209 (SE 0.6%) received a PA catheter. In 2001, the number of hospitals with ≥1 PA catheterization was 1753, decreasing to 1183 in 2011. The mean PA catheter use per hospital trended from 4.9 per year in 2001 (limits 1–133) to 3.8 per year in 2007 (limits 1–46), but increased to 5.5 per year in 2011 (limits 1–70). During 2001 to 2006, PA catheterization declined across hospitals; however, in 2007 to 2012, there was a disproportionate increase at hospitals with large bedsize, teaching programs, and advanced HF capabilities. The overall in-hospital mortality with PA catheter use was higher than without PA catheter use (13.1% versus 3.4%; P<0.0001); however, in propensity-matched analysis, differences in mortality between these groups have attenuated over time—risk-adjusted odds ratio for mortality for PA catheterization, 1.66 (95% confidence interval, 1.60–1.74) in 2001 to 2003 down to 1.04 (95% confidence interval, 0.97–1.12) in 2010 to 2012. Conclusions—There is substantial hospital-level variability in PA catheterization in HF along with increasing volume at fewer hospitals over-represented by large, academic hospitals with advanced HF capabilities. This is accompanied by a decline in excess mortality associated with PA catheterization.
Acute Inhibition of Na/H Exchanger NHE-3 by cAMP

Regulation of the renal Na/H exchanger NHE-3 by protein kinase A (PKA) is a key intermediate step in the hormonal regulation of acid-base and salt balance. We studied the role of NHE-3 phosphorylation in this process in NHE-deficient AP-1 cells transfected with NHE-3 and in OKP cells expressing native NHE-3. A dominant-negative PKA-regulatory subunit completely abolished the effect of cAMP on NHE-3 activity demonstrating a role of PKA in the functional regulation of NHE-3 by cAMP. NHE-3 isolated from cAMP-treated cells showed lower phosphorylation by purified PKAin vitro suggesting that NHE-3 is a PKA substrate in vivo. Although changes in NHE-3 whole protein phosphorylation is difficult to detect in response to cAMP addition, the tryptic phosphopeptide map of in vivo phosphorylated NHE-3 showed a complex pattern of constitutive and cAMP-induced phosphopeptides. To test the causal relationship between phosphorylation and activity, we mutated eight serines in the cytoplasmic domain to glycine or alanine. Single or multiple mutants harboring S552A or S605G showed no PKA activation or reduced regulation by PKA activation. Ser-552 and Ser-605 were phosphorylated in vivo. However, multiple mutations of serines other than Ser-552 or Ser-605 also reduced the functional PKA regulation. We conclude that regulation of NHE-3 by PKA in vivo involves complex mechanisms, which include phosphorylation of Ser-552 and Ser-605.
Innate immune recognition of flagellin limits systemic persistence of Brucella

Brucella are facultative intracellular bacteria that cause chronic infections by limiting innate immune recognition. It is currently unknown whether Brucella FliC flagellin, the monomeric subunit of flagellar filament, is sensed by the host during infection. Here, we used two mutants of Brucella melitensis, either lacking or overexpressing flagellin, to show that FliC hinders bacterial replication in vivo. The use of cells and mice genetically deficient for different components of inflammasomes suggested that FliC was a target of the cytosolic innate immune receptor NLRC4 in vivo but not in macrophages in vitro where the response to FliC was nevertheless dependent on the cytosolic adaptor ASC, therefore suggesting a new pathway of cytosolic flagellin sensing. However, our work also suggested that the lack of TLR5 activity of Brucella flagellin and the regulation of its synthesis and/or delivery into host cells are both part of the stealthy strategy of Brucella towards the innate immune system. Nevertheless, as a flagellin‐deficient mutant of B. melitensis wasfound to cause histologically demonstrable injuries in the spleen of infected mice, we suggested that recognition of FliC plays a role in the immunological stand‐off between Brucella and its host, which is characterized by a persistent infection with limited inflammatory pathology.
Microparticles as vaccine adjuvants and delivery systems

Adjuvants can be broadly divided into two groups, based on their principal mechanisms of action: vaccine delivery systems and immunostimulatory adjuvants. Vaccine delivery systems are generally particulate (e.g., emulsions, microparticles, immunostimulatory complexes and liposomes) and function mainly to target associated antigens into antigen-presenting cells. However, increasingly, more complex formulations are being developed in which delivery systems are exploited both for the delivery of antigens and also for the delivery of coadministered immunostimulatory adjuvants. The rationale for this approach is to ensure that both antigen and adjuvant are delivered into the same population of antigen-presenting cells. In addition, delivery systems can focus the effect of the adjuvants onto the key cells of the immune system and limit the systemic distribution of the adjuvant, to minimize its potential to induce adverse effects. The formulation and delivery of potent adjuvants in microparticles may allow the development of prophylactic and therapeutic vaccines against cancers and chronic infectious diseases, which are currently poorly controlled. In addition, microparticle formulations may also allow vaccines to be delivered mucosally.
Urinary Porphyrin Excretion in Children with Mercury Amalgam Treatment: Findings from the Casa Pia Children's Dental Amalgam Trial

Increases in the urinary concentrations of pentacarboxyl- and coproporphyrins and the appearance of the atypical precoproporphyrin have been defined in relation to mercury (Hg) body burden in animal studies, and this change in the porphyrin excretion pattern has been described as a biomarker of occupational Hg exposure and toxicity in adult human subjects. In the present studies, urinary porphyrins were determined in relation to Hg exposure in children and adolescents, 8–18 yr of age, over the 7-yr course of a clinical trial designed to evaluate the neurobehavioral and renal effects of dental amalgam in children. Subjects were randomized to either dental amalgam or composite resin treatments. Urinary porphyrins and creatinine concentrations were measured at baseline and annually in all subjects. Results were evaluated using linear regression analysis. No significant differences between treatment groups (amalgam versus composite) were found when comparing all subjects for any of the porphyrins of interest. However, incipent amalgam treatment-specific increases were observed in the mean concentrations of penta-, precopro- and coproporphyrins especially when the analyses were restricted to younger subjects (8 to 9 yr old at baseline), and these increases were most apparent during yr 2 through 3 of follow-up, the period of highest mercury exposure from amalgam treatment. Based on the mean number of amalgam fillings received by children in this group (17.8), the renal Hg concentration associated with incipient increases in urinary porphyrins was estimated to be approximately 2.7 μg/g renal cortex. This value corresponds to an observed mean urinary Hg concentration of 3.2 μg/g creatinine, which is approximately fivefold less than that at which renal damage from Hg exposure is estimated to occur in children. These findings are consistent with growing evidence supporting the sensitivity of urinary porphyrins as a biological indicator of subclinical Hg exposure in children.
Changes in fatty acid synthesis associated with growth and fattening

During growth and fattening, differences exist in the way nutrients are partitioned for deposition as fat and muscle protein. Knowledge of the partitioning of energy is of practical significance in the production of lean animals. In this review, emphasis will be placed on changes in fatty acid synthesis which occur during the growth and fattening of animals grown for meat, and on factors affecting these changes.
Awareness among nurses about reporting of adverse drug reactions in Sweden

Background The purpose of this study was to investigate awareness among nurses regarding their new role as reporters of adverse drug reactions in Sweden and factors that may influence reporting by nurses. Methods In 2007, all nurses were included in the adverse drug reaction reporting scheme in Sweden. A questionnaire was sent to 753 randomly selected nurses in September 2010. Results Of the 453 (60%) responding nurses, 265 (58%) were aware that nurses were included in the reporting of adverse drug reactions. Sixty-one nurses (14%) stated that they had reported an adverse drug reaction. Fifteen percent (n = 70) of the respondents had received training about reporting of adverse drug reactions. Almost one third of these (n = 21, 30%) had reported an adverse drug reaction on at least one occasion. Among nurses without training, a smaller proportion (n = 40, 11%, P < 0.05) had reported an adverse drug reaction on at least one occasion. The two factors considered most important by nurses for reporting were the severity of the adverse drug reaction and if the reaction was to a newly approved drug. A majority of the nurses (n = 397, 88%) were interested in a training course in pharmacology as part of their ongoing professional development. One third (32%) of all nurses stated that one reason for not reporting a suspected adverse drug reaction was that the physician responsible did not regard the reaction necessary to report. Conclusion We found that more than half of the study population of nurses in Sweden were aware of their new role as reporters of adverse drug reactions, but few of the responding nurses had reported an adverse drug reaction. Given that training seems to be associated with high reporting frequency, we suggest more training in pharmacovigilance for nurses.
Hemolytic Uremic Syndrome After an Escherichia coli O111 Outbreak.

BACKGROUND In August 2008, the largest known US serotype 1 Escherichia coli O111 outbreak occurred in Oklahoma, causing 341 illnesses, including hemolytic uremic syndrome (HUS). HUS is not well described in non-O157 E coli outbreaks but occurs in 2% to 15% of O157 infections, predominantly among children. We examined outbreak-related hospitalizations to characterize E coli O111 illness, the HUS attack rate, and factors associated with subsequent HUS diagnosis among hospitalized patients. METHODS Medical records were reviewed for clinical presentation and evidence of HUS among hospitalized patients identified during the outbreak investigation. Characteristics of hospitalized patients with vs without HUS were compared. RESULTS HUS was identified in 26 of 156 (16.7%) confirmed or probable E coli O111 infections; 65.4% of patients with HUS required dialysis, and 1 patient died. The median age of patients with HUS was 43.5 years (age range, 1-88 years); adults composed 57.7% of HUS cases. Characteristics at hospital admission associated with subsequent HUS diagnosis included white blood cell count of at least 20 000/μL (adjusted odds ratio [aOR], 11.3; 95% confidence interval [CI], 1.7-75.3), elevated serum creatinine level for age (9.7; 1.4-69.2), and vomiting before hospital admission (6.8; 1.5-31.3). Administration of antimicrobial agents (risk ratio [RR], 1.0; 95% CI, 0.5-1.8) or medication with antimotility effects (1.4; 0.6-2.9) was not associated with subsequent HUS. CONCLUSIONS The HUS attack rate in this E coli O111 outbreak was comparable to that for E coli O157-related illnesses, but most cases occurred among adults. On admission, factors associated with subsequent HUS can identify patients who require close monitoring and early aggressive supportive care to improve outcomes.
On the Potential of Simple Framewise Approaches to Piano Transcription

In an attempt at exploring the limitations of simple approaches to the task of piano transcription (as usually defined in MIR), we conduct an in-depth analysis of neural network-based framewise transcription. We systematically compare different popular input representations for transcription systems to determine the ones most suitable for use with neural networks. Exploiting recent advances in training techniques and new regularizers, and taking into account hyper-parameter tuning, we show that it is possible, by simple bottom-up frame-wise processing, to obtain a piano transcriber that outperforms the current published state of the art on the publicly available MAPS dataset -- without any complex post-processing steps. Thus, we propose this simple approach as a new baseline for this dataset, for future transcription research to build on and improve.
Rheumatoid factor revisited

Purpose of reviewInitial studies of the pathogenesis of rheumatoid arthritis focused on the role of rheumatoid factor and immune complex–associated vasculitis and synovitis. Subsequent work has delineated T cell responses, the role of cytokines, chemokines, and the aggressive nature of rheumatoid synovitis. Recent findings underscore the importance of humoral immunity in this entity and are the subject of this review. Recent findingsBy the discovery of anti–cyclic citrullinated peptide, anti-RA33, and anti-GPI antibodies in the human and mouse systems, respectively, the impact of humoral autoimmunity in rheumatoid arthritis regained remarkable interest. This review summarizes recent insights into humoral autoimmunity in rheumatoid arthritis in the context of the generation of rheumatoid factors, including B cell activation via toll-like receptors and genetic predispositions that can trigger the induction of rheumatoid arthritis. The generation of rheumatoid factors that can also be found during host defense against infectious agents and under pathologic conditions, such as rheumatoid arthritis, Sjögren syndrome, and hepatitis C–associated mixed cryoglobulinemia after hepatitis C infection is likely the result of genetic predispositions and the intensity of the (primary) immune reaction. Models of the role of rheumatoid factors in health and disease, including related lymphomagenesis, will be discussed. SummaryIn patients with rheumatoid arthritis, the induction of rheumatoid factors can be taken as an indicator of severe disease with a striking involvement of B cell activation. Very recent clinical trials using B cell depletion support the concept that humoral immunity, as evidenced by the production of rheumatoid factors, plays a significant role in the course of the disease.
Interface Theories for (A)synchronously Communicating Modal I/O-Transition Systems

Interface specifications play an important role in component-based software development. An interface theory is a formal framework supporting composition, refinement and compatibility of interface specifications. We present different interface theories which use modal I/O-transition systems as their underlying domain for interface specifications: synchronous interface theories, which employ a synchronous communication schema, as well as a novel interface theory for asynchronous communication where components communicate via FIFO-buffers.
Thinking Critically About Armed Groups and Human Rights Praxis

This article critically examines the relationship between the human rights movement and armed groups. Drawing upon a wide array of case studies, it examines some of the most important legal and policy developments which have shaped this field since the 1980s. It also critically explores some of the theoretical and practical models of interventions which have been deployed by different human rights organizations concerning abuses by armed groups. The paper then explores the dilemmas of engagement with armed groups while managing the difficulties associated with conferring legitimacy on such groups. It also explores how human rights groups deal with the realities of the involvement of some armed groups in governance functions within their own communities. Finally, we identify two areas where we believe important future developments in this field could be directed: the framework of transitional justice, and the role of human rights organizations in navigating the increasingly blurred boundaries between some armed groups and organized crime
Clarification of the pH-dependent kinetic behaviour of papain by using reactivity probes and analysis of alkylation and catalysed acylation reactions in terms of multihydronic state models: implications for electrostatics calculations and interpretation of the consequences of site-specific mutations

1. The complex behaviour of papain (EC 3.4.22.2) in acidic media has been investigated by (a) stopped-flow reactivity probe kinetics using 4,4'-dipyrimidyl disulphide (I) and 2,2'-dipyridyl disulphide (II) as thiol-specific time-dependent inhibitors with markedly different susceptibilities to activation by hydronation (protonation) and (b) using the multitasking application program SKETCHER for the rapid evaluation of pH-dependent kinetic data by means of interactive manipulation of calculated curves. 2. The substantially lower basicity of (I) (pKa 0.91) than that of (II) (pKa 2.45) combined with retention of high reactivity permitted the pKa for the formation of the (Cys-25)-S-/(His-159)-Im+H ion-pair state of papain to be determined kinetically as 3.4, a value close to that (3.3) deduced by potentiometric difference titration [Lewis, Johnson and Shafer (1976) Biochemistry 15, 5009-5017] and lower than the value (approx. 4) often reported from pH-dependent kinetic studies. The higher values are now known to arise from inadequate data analysis that does not take account of other overlapping kinetically influential ionizations. 3. Re-evaluation of the extensive sets of pH-kcat/Km data for the hydrolysis of nine substrates by papain reported by Polgár and Halász (1978) (Eur. J. Biochem. 88, 513-521) by making use of SKETCHER, the known pKa value (3.4) from the reaction with compound (I) and two additional kinetically influential pKa values deduced from the reaction with compound (II) now permits the identification of the pH-dependent events in reactions of papain with inhibitors and substrates. 4. A major conclusion is that, whereas in reactions of simple alkylating agents and compound (I) full nucleophilic character of (Cys-25)-S-/(His-159)-Im+H is provided by hydronic dissociation with pKa 3.3-3.4, in catalysis relatively little catalytic competence is produced consequent upon ion-pair formation. Substantial catalytic competence requires further hydronic dissociation with pKa approx. 4, and for cationic substrates further enhancement is produced by hydronic dissociation with pKa approx. 5. 5. The present work, together with the kinetic analysis of reactions of papain in alkaline media reported by Mellor, Thomas, Topham and Brocklehurst [Biochem. J. (1993) 290, 289-296], defines the kinetically influential ionizations of papain as 3.4, 4.0, 5.0, 8.3 and 10.0 of which 3.4 and 8.3 relate to the formation and subsequent dehydronation of the ion-pair state. (ABSTRACT TRUNCATED AT 400 WORDS)
Heme as an optical probe of a conformational transition of ovine recPrP

The prion protein occurs as a globular domain and a leading fragment whose structure is not well‐defined. For the ovine species, all of the tryptophan residues are in the initial fragment, while the globular domain is rich in tyrosine residues. Using heme as a spectroscopic probe, we have studied the recombinant prion protein before and after a temperature‐induced conformational change. As for most heme proteins, the absorption spectrum of heme‐CO displays a red shift upon binding to the protein, and both the Y and W fluorescence are highly quenched. Flash photolysis kinetics of the PrP–heme‐CO complex shows a low yield for the bimolecular phase, indicating a pocket around the hemes. By comparing the holoprotein and the truncated sequence corresponding to the globular domain, the stoichiometry was determined to be five hemes for the globular domain and two hemes for the leading fragment. At high temperature, the hemes are released; upon cooling, only two hemes bind, and only the tryptophan fluorescence is quenched; this would indicate that the globular domain has formed a more compact structure, which is inert with respect to the hydrophobic probe. The final state of polymerization is perturbed if the synthetic peptide “N3” (PrP residues 142–166, which include the first helix) is added to the prion protein solution; the temperature cycle no longer reduces the number of heme binding sites. This would indicate that the peptide may alter or inhibit the polymer formation.
Individual tables of contents in Web-based learning systems

The iTeach project of the Darmstadt University of Technology builds a webbased adaptive hypermedia teaching and learning environment for multimedia and communication technology. Hereby, the demands of diverse user groups, user levels and especially of diverse learning strategies are taken into account. Besides information gained from the interaction with the user, the system uses standardized content relations and meta-information to adaptively compile a selection from the set of available information units (media bricks). A subset of the metainformation represents the compiled lesson on a high level and is presented to the learner as a dynamically generated table of contents. Subjects which are topics in one scenario can be subtopic in the next or not occur at all. Our approach can help closing the gap between free navigation and static guidance in an adaptive hypermedia system.
Cleavage furrow positioning

To complete the cell cycle, the cleavage furrow draws the plasma membrane toward the cell center, pinching the cytoplasm into two lobes that are subsequently separated into two cells. The position of the cleavage furrow is induced by the mitotic spindle during early anaphase. Although the mechanism of cleavage furrow positioning is not understood at a molecular level, recent results suggest that it might be mediated by local relief from the inhibitory effects of microtubules.
A framework for analyzing the propagation of hardware-induced errors in non-recursive LTI blocks with finite wordlength effects

Modern digital designs, beyond adopting measures for energy-, area-efficiency and performance, have to adopt additional measures for a more robust functionality throughout their lifetime. On the way to finding cost-effective resilience approaches, an important first step is to analyze the system behavior in the presence of errors. This gives insight to the system designers regarding the criticality of the system nodes and, so, more targeted and efficient measures can be applied. However, given the complexity of modern systems and the abundance of potential vulnerable parts, typical approaches that perform such analysis rely on system simulation and lack scalability. Alternative solutions are required that go beyond the traditional, time-consuming simulation experiments. This paper proposes a framework to handle in a scalable way error injection and propagation through linear time invariant blocks in presence of finite wordlength effects.