bluuebunny/crossref_metadata_2025_split huggingface dataset:
Markers of Plaque Instability in the Early Diagnosis and Risk Stratification of Acute Myocardial Infarction
Authors: Schaub Nora , Reichlin Tobias , Meune Christophe , Twerenbold Raphael , Haaf Philip , Hochholzer Willibald , Niederhauser Nadine , Bosshard Piet , Stelzig Claudia , Freese Michael , Reiter Miriam , Gea Joachim , Buser Andreas , Mebazaa Alexandre , Osswald Stefan , Mueller Christian 
Published: November 2011

Abstract

BACKGROUND
Plaque erosion and plaque rupture occur early in the pathophysiology of acute myocardial infarction (AMI). We hypothesized that markers of plaque instability might be useful in the early diagnosis and risk stratification of AMI.

METHODS
In this multicenter study, we examined 4 markers of plaque instability, myeloperoxidase (MPO), myeloid-related protein 8/14 (MRP-8/14), pregnancy-associated plasma protein-A (PAPP-A), and C-reactive protein (CRP) in 398 consecutive patients presenting to the emergency department with acute chest pain and compared them to normal and high-sensitivity cardiac troponin T (cTnT and hs-cTnT). The final diagnosis was adjudicated by 2 independent cardiologists. Primary prognostic end point was death during a median follow-up of 27 months.

RESULTS
The adjudicated final diagnosis was AMI in 76 patients (19%). At emergency department presentation, concentrations of all 4 biomarkers of plaque instability were significantly higher in patients with AMI than in patients with other diagnoses. However, their diagnostic accuracy as quantified by the area under the ROC curve (AUC) was low (MPO 0.63, MRP-8/14 0.65, PAPP-A 0.62, CRP 0.59) and inferior to both normal and high-sensitivity cardiac troponin T (cTnT 0.88, hs-cTnT 0.96; P &lt; 0.001 for all comparisons). Thirty-nine patients (10%) died during follow-up. Concentrations of MPO, MRP-8/14, and CRP were higher in nonsurvivors than in survivors and predicted all-cause mortality with moderate accuracy.

CONCLUSIONS
Biomarkers of plaque instability do not seem helpful in the early diagnosis of AMI but may provide some incremental value in the risk stratification of patients with acute chest pain.
Glucagon counteracts interleukin-6-dependent gene expression by redundant action of Epac and PKA
Authors: Khouri Christina , Dittrich Anna , Sackett Sara Dutton , Denecke Bernd , Trautwein Christian , Schaper Fred 
Published: November 2011

Abstract
Inflammation is the biological response to injurious stimuli. In the initial phase of the inflammatory process, interleukin-6 (IL-6) is the main inducer of acute phase protein expression in the liver. A prolonged acute phase response is characterised by a disturbed glucose homeostasis and elevated levels of IL-6, insulin, and counterregulatory hormones such as glucagon. Several studies deal with the impact of IL-6 on glucagon-dependent gene expression. In contrast, only very little is known about the influence of G-protein-coupled receptors on IL-6 signalling. Therefore, the aim of this study is to elucidate the regulation of IL-6-induced gene expression by glucagon. We could reveal a novel mechanism of negative regulation of IL-6-induced MAP kinase activation by glucagon in primary murine hepatocytes. IL-6-dependent induction of the ERK-dependent target gene Tfpi2, coding for a Kunitz-type serine protease inhibitor, was strongly down-regulated by glucagon treatment. Studying the underlying mechanism revealed a redundant action of the signalling molecules exchange protein activated by cyclic AMP (Epac) and protein kinase A. The metabolic hormone glucagon interferes in IL-6-induced gene expression. This observation is indicative for a regulatory role of G-protein-coupled receptors in the IL-6-dependent inflammatory response.
Dimerization of human 5-lipoxygenase
Authors: Häfner Ann-Kathrin , Cernescu Mihaela , Hofmann Bettina , Ermisch Michael , Hörnig Michael , Metzner Julia , Schneider Gisbert , Brutschy Bernhard , Steinhilber Dieter 
Published: November 2011

Abstract
Human 5-lipoxygenase (5-LO) can form dimers as shown here via native gel electrophoresis, gel filtration chromatography and LILBID (laser induced liquid bead ion desorption) mass spectrometry. After glutathionylation of 5-LO by diamide/glutathione treatment, dimeric 5-LO was no longer detectable and 5-LO almost exclusively exists in the monomeric form which showed full catalytic activity. Incubation of 5-LO with diamide alone led to a disulfide-bridged dimer and to oligomer formation which displays a strongly reduced catalytic activity. The bioinformatic analysis of the 5-LO surface for putative protein-protein interaction domains and molecular modeling of the dimer interface suggests a head to tail orientation of the dimer which also explains the localization of previously reported ATP binding sites. This interface domain was confirmed by the observation that 5-LO dimer formation and inhibition of activity by diamide was largely prevented when four cysteines (C159S, C300S, C416S, C418S) in this domain were mutated to serines.
Cysteine proteinase SpeB from Streptococcus pyogenes – a potent modifier of immunologically important host and bacterial proteins
Authors: Nelson Daniel C. , Garbe Julia , Collin Mattias 
Published: November 2011

Abstract
Group A streptococcus (Streptococcus pyogenes) is an exclusively human pathogen that causes a wide spectrum of diseases ranging from pharyngitis, to impetigo, to toxic shock, to necrotizing fasciitis. The diversity of these disease states necessitates that S. pyogenes possess the ability to modulate both the innate and adaptive immune responses. SpeB, a cysteine proteinase, is the predominant secreted protein from S. pyogenes. Because of its relatively indiscriminant specificity, this enzyme has been shown to degrade the extracellular matrix, cytokines, chemokines, complement components, immunoglobulins, and serum protease inhibitors, to name but a few of the known substrates. Additionally, SpeB regulates other streptococcal proteins by degrading them or releasing them from the bacterial surface. Despite the wealth of literature on putative SpeB functions, there remains much controversy about this enzyme because many of reported activities would produce contradictory physiological results. Here we review all known host and bacterial protein substrates for SpeB, their cleavage sites, and discuss the role of this enzyme in streptococcal pathogenesis based on the current literature.
Synthesis of novel-9-cyano/acetylpyrano[2,3-f]chromones via Baylis-Hillman reaction
Authors: Jayaprakash Rao Y. , Niranjan K. , Hemasri Y. , David Krupadanam G.L. 
Published: November 2011

Abstract
Condensation of 8-formyl-7-hydroxy chromones 2a–e with methyl vinyl ketone and acrylonitrile in the presence of diazabicyclo[2.2.2]octane (DABCO) under Baylis-Hillman reaction conditions afforded 9-cyano/acetyl-substituted pyrano[2,3-f]chromones 3a–e and 4a–e.
The need for evidence-based, non-drug medicine
Authors: Ventegodt Søren , Orr Gary , Merrick Joav 
Published: November 2011

Abstract
Evidence-based medicine (EBM) is defined as “the integration of best research evidence with clinical expertise and patient values.” EBM is based on three equally important key factors: i) the best available scientific evidence; ii) the physician’s experience and intuition; and, iii) the preferences and values of the patient. EBM uses a hierarchy of evidence and critical appraisal of the sources, which makes it possible to balance high quality evidence with documented effectiveness. A treatment that is more safe and effective, but less well documented may very well be the treatment of choice. Ethics (not putting the patient at risk of harm with a treatment if this can be avoided at all) is an important part of EBM. Many pharmaceutical drugs have a number needed to treat (NNT) of approximately 20 [NNT=20, confidence interval CI (5–50)] and the number needed to harm is less well understood and documented. The adverse effect profile of pharmacological agents can be more harmful than non-drug medicine. Most EBM-treatments are likely to be non-drug treatments in the future. There are six steps to the practice of EBM: i) the patients and the physician must work together to define the problem; ii) the patients and the physician must explore the patient’s values and preferences; iii) the information about the possible alternative medical interventions must be discussed and critically appraised; iv) the best, relevant evidence must be applied to the patient as a treatment or cure; v) together, the patient and the physician must evaluate how useful the intervention was; and vi) if the intervention did not help sufficiently, the process must begin again. In this review, we explain, in our opinion, how non-drug EBM should be practiced.
Transcriptional Regulation and the Diversification of Metabolism in Wine Yeast Strains
Authors: Rossouw Debra , Jacobson Dan , Bauer Florian F 
Published: November 2011

AbstractTranscription factors and their binding sites have been proposed as primary targets of evolutionary adaptation because changes to single transcription factors can lead to far-reaching changes in gene expression patterns. Nevertheless, there is very little concrete evidence for such evolutionary changes. Industrial wine yeast strains, of the species Saccharomyces cerevisiae, are a geno- and phenotypically diverse group of organisms that have adapted to the ecological niches of industrial winemaking environments and have been selected to produce specific styles of wine. Variation in transcriptional regulation among wine yeast strains may be responsible for many of the observed differences and specific adaptations to different fermentative conditions in the context of commercial winemaking. We analyzed gene expression profiles of wine yeast strains to assess the impact of transcription factor expression on metabolic networks. The data provide new insights into the molecular basis of variations in gene expression in industrial strains and their consequent effects on metabolic networks important to wine fermentation. We show that the metabolic phenotype of a strain can be shifted in a relatively predictable manner by changing expression levels of individual transcription factors, opening opportunities to modify transcription networks to achieve desirable outcomes.
Measuring Selection Coefficients Below 10−3: Method, Questions, and Prospects
Authors: Gallet Romain , Cooper Tim F , Elena Santiago F , Lenormand Thomas 
Published: November 2011

Abstract
Measuring fitness with precision is a key issue in evolutionary biology, particularly in studying mutations of small effects. It is usually thought that sampling error and drift prevent precise measurement of very small fitness effects. We circumvented these limits by using a new combined approach to measuring and analyzing fitness. We estimated the mutational fitness effect (MFE) of three independent mini-Tn10 transposon insertion mutations by conducting competition experiments in large populations of Escherichia coli under controlled laboratory conditions. Using flow cytometry to assess genotype frequencies from very large samples alleviated the problem of sampling error, while the effect of drift was controlled by using large populations and massive replication of fitness measures. Furthermore, with a set of four competition experiments between ancestral and mutant genotypes, we were able to decompose fitness measures into four estimated parameters that account for fitness effects of our fluorescent marker (α), the mutation (β), epistasis between the mutation and the marker (γ), and departure from transitivity (τ). Our method allowed us to estimate mean selection coefficients to a precision of 2 × 10−4. We also found small, but significant, epistatic interactions between the allelic effects of mutations and markers and confirmed that fitness effects were transitive in most cases. Unexpectedly, we also detected variation in measures of s that were significantly bigger than expected due to drift alone, indicating the existence of cryptic variation, even in fully controlled experiments. Overall our results indicate that selection coefficients are best understood as being distributed, representing a limit on the precision with which selection can be measured, even under controlled laboratory conditions.
Survival Prediction for Terminally Ill Cancer Patients: Revision of the Palliative Prognostic Score with Incorporation of Delirium
Authors: Scarpi Emanuela , Maltoni Marco , Miceli Rosalba , Mariani Luigi , Caraceni Augusto , Amadori Dino , Nanni Oriana 
Published: November 2011

AbstractLearning ObjectivesAfter completing this course, the reader will be able to: Describe the effect on the palliative prognostic score classifications when delirium was included as a variable.Compare changes in overall survival times when delirium was added to the palliative prognostic score.CME This article is available for continuing medical education credit at CME.TheOncologist.comPurpose.An existing and validated palliative prognostic (PaP) score predicts survival in terminally ill cancer patients based on dyspnea, anorexia, Karnofsky performance status score, clinical prediction of survival, total WBC, and lymphocyte percentage. The PaP score assigns patients to three different risk groups according to a 30-day survival probability—group A, &gt;70%; group B, 30%–70%; group C, &lt;30%. The impact of delirium is known but was not incorporated into the PaP score.Materials and Methods.Our aim was to incorporate information on delirium into the PaP score based on a retrospective series of 361 terminally ill cancer patients. We followed the approach of “validation by calibration,” proposed by van Houwelingen and later adapted by Miceli for achieving score revision with inclusion of a new variable. The discriminating performance of the scores was estimated using the K statistic.Results.The prognostic contribution of delirium was confirmed as statistically significant (p &lt; .001) and the variable was accordingly incorporated into the PaP score (D-PaP score). Following this revision, 30-day survival estimates in groups A, B, and C were 83%, 50%, and 9% for the D-PaP score and 87%, 51%, and 16% for the PaP score, respectively. The overall performance of the D-PaP score was better than that of the PaP score.Conclusion.The revision of the PaP score was carried out by modifying the cutoff values used for prognostic grouping without, however, affecting the partial scores of the original tool. The performance of the D-PaP score was better than that of the PaP score and its key feature of simplicity was maintained.
Acinar Cell Carcinoma of the Pancreas: New Genetic and Treatment Insights into a Rare Malignancy
Authors: Lowery Maeve A. , Klimstra David S. , Shia Jinru , Yu Kenneth H. , Allen Peter J. , Brennan Murray F. , O'Reilly Eileen M. 
Published: November 2011

Abstract

Background.
Acinar cell carcinoma (ACC) of the pancreas is a rare neoplasm, accounting for 1% of all pancreatic neoplasms. There remains a lack of data regarding the use of systemic therapy in this disease. We present a series of 40 consecutive cases of ACC of the pancreas treated at Memorial Sloan-Kettering Cancer Center, with an emphasis on evaluation of activity of new therapeutic agents.

Methods.
Patients reviewed at our institution from January 2000 through January 2011 were identified from an institutional database with prior institutional review board approval. Pathology was confirmed in all cases as ACC or a closely related entity.

Results.
Forty patients were identified; 29 were male (73%). The median age at diagnosis was 65 years (range, 16–87 years). The median overall survival (OS) time for patients with localized, resectable disease was 56.9 months and the OS time for patients with metastatic ACC (n = 18) was 19.6 months. Six patients with metastatic or recurrent ACC had a partial response to chemotherapy and five patients had stable disease for ≥6 months on systemic chemotherapy. Clinical observation was made of a patient with ACC and hereditary nonpolyposis colorectal cancer and a patient with ACC and a BRCA1 germline mutation.

Conclusions.
ACC is moderately chemoresponsive to agents that have activity in pancreatic adenocarcinoma and colorectal carcinoma. A potential association between germline mutations in DNA mismatch repair genes and ACC warrants further evaluation.
Northeast Pacific Cretaceous record ofPyropsis(Neogastropoda: Pyropsidae) and paleobiogeography of the genus
Authors: Squires Richard L. 
Published: November 2011

The neogastropod genusPyropsisConrad, 1860 (family Pyropsidae Stephenson, 1941) is recognized for the first time from Upper Cretaceous shallow-marine siliciclastic rocks in the region extending from Vancouver Island, British Columbia southward to southern California. Four new species were detected:Pyropsis aldersoni(earliest Coniacian, southern California),Pyropsis californica(early Coniacian, northern California),Pyropsis louellae(late Coniacian or early Santonian, northern California), andPyropsis grahami(late early Campanian, Vancouver Island).A critical review of the global reports ofPyropsis, a genus that has been commonly confused with other genera (especiallyTudiclaRöding, 1798), establishes thatPyropsishad an amphitropical distribution and lived in warm-temperate waters adjacent to a broad tropical realm. It is rare to uncommon wherever found, and its geologic range is middle Cenomanian to an age near the Cretaceous/Paleogene boundary (probably earliest Paleocene). It was moderately widespread before the Maastrichtian but was predominantly restricted to the New World during the Maastrichtian.
A new genus of nautiloid in the Toarcian of the Iberian peninsula (Spain and Portugal)
Authors: Barroso-Barcenilla Fernando , Comas-Rengifo María José , Duarte Luís Vítor , Goy Antonio , Martínez Gemma 
Published: November 2011

Abstract
Historically, most of the nautiloids arisen during the Early Jurassic have been assigned initially to the genus NautilusLinnaeus, 1758, and subsequently to CenocerasHyatt, 1884. At present, a tendency to rehabilitate other genera or to describe new ones predominates among the few authors who try to classify and to group these problematic cephalopods. In the present work, the new genus Ligeiceras has been described for remarkably small and involute nautiloids with notably retrogressive suture lines. It has a smooth or slightly ornamented external surface, limited to thin tenuous, ventraly retroverse and distant growth lines and longitudinal and transversal striae. This group, seemingly, appeared after the biotic crisis of the end of the Tenuicostatum/Polymorphum Zone, evolved during the radiation of the Early Toarcian Serpentinum/Levisoni Zone and the Late Toarcian, and survived at least until the Aalenian. New specimens from the Iberian peninsula (Basque-Cantabrian and Iberian basins, Spain; and Lusitanian basin, Portugal), belonging to the taxa Nautilus fournetiDumortier, 1874 (selected as type species), Nautilus inornatusd’Orbigny, 1843, Nautilus anomphalusPia, 1914, Nautilus jurensisQuenstedt, 1846-49, and, with doubts, Cenoceras globulusRulleau, 2008, have been collected, described and assigned to this systematic group. Although some of these species have already been cited in the literature, Ligeiceras fourneti, Ligeiceras jurensis and Ligeiceras? globulus have never been previously clearly described or illustrated, and their stratigraphic distribution has not been determined accurately for the Iberian peninsula, as has been done here for these taxa and for Ligeiceras inornatus and Ligeiceras anomphalus. Therefore, the present work on the new genus Ligeiceras constitutes a notable advance in the knowledge of these nautiloids, and seems to confirm that the dwarfism could have been a relatively generalized tendency in the Upper Toarcian of southwestern Europe, possibly due to palaeoenvironmental causes.
Taphonomic analysis and sequence stratigraphy of the Albarracinites beds (lower Bajocian, Iberian range, Spain). An example of shallow condensed section
Authors: Fernández-López Sixto Rafael 
Published: November 2011

AbstractSeveral ammonite fossil assemblages from Sierra de Albarracín (Teruel, Castilian Branch) contain abundant specimens of the Ovale and Laeviuscula zones (lower Bajocian, Middle Jurassic), including microconchs and macroconchs of the characteristic genus Albarracinites. Over 1500 ammonites from the type horizon of the species A. albarraciniensis, in the outcrop of Masada Toyuela, have been studied.Ammonites are commonly preserved as phosphatized, calcareous, concretionary internal moulds (mean size = 50.5 mm) of unflattened shells, partially or completely filled with relatively heterogeneous mudstone to wackestone sediment. Incomplete, fragmented phragmocones with calcitic septa are the dominant remains, generally bearing traces of rounding, incrustation and bioerosion. Taphonomic data, such as the predominant taphonomic populations of type 3, composed of reelaborated, relatively heterogeneous concretionary internal moulds, isolated concretionary body chambers and hollow ammonites, bearing traces of abrasion, bioerosion and encrusting organisms, are indicative of low rate of sedimentation and occasional high rate of sediment accumulation, due to sedimentary winnowing and bypassing interrupted by storm depositional events, in shallow-water marine environments. The exceptional occurrence of taphonic populations of type 2 belonging to Albarracinites and Hebetoxyites, with dominant shells of pre-adults and absence of juveniles, suggests autochthonous biogenic production of shells by indigenous populations of Sub-Mediterranean taxa at the Iberian platform system.In the outcrop of Masada Toyuela, the Albarracinites beds correspond to a condensed section, developed in shallow-water, open-marine, carbonate environments of the External Castilian platform. The sharp, irregular base of beds and the normal grading of reworked elements suggest these carbonate deposits were affected by tractive currents, scouring and redeposition. Limestone beds represent storm-related sedimentary events, whereas the local marly intervals represent background-sedimentation time-intervals of winnowing and bypassing on the seafloor. This condensed section is composed of at least four, decimetric or centimetric, expanded-deposit intervals, stacked and showing an overall thinning upward, which constitute a deepening sequence developed during two biochrons. Taphonomic results also corroborate the development of an incipient-deepening phase, which represents the first episode of a deepening half-cycle of third order, in the Albarracín area within the Castilian platform, during the Ovale and Laeviuscula biochrons (early Bajocian).