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Background: Prevention of persistent pain following breast cancer surgery, via early identification of patients at high risk, is a clinical need. Supervised machine-learning was used to identify parameters that predict persistence of significant pain.
Methods: Over 500 demographic, clinical and psychological parameters were acquired up to 6 months after surgery from 1,000 women (aged 28–75 years) who were treated for breast cancer. Pain was assessed using an 11-point numerical rating scale before surgery and at months 1, 6, 12, 24, and 36. The ratings at months 12, 24, and 36 were used to allocate patents to either "persisting pain" or "non-persisting pain" groups. Unsupervised machine learning was applied to map the parameters to these diagnoses.
Results: A symbolic rule-based classifier tool was created that comprised 21 single or aggregated parameters, including demographic features, psychological and pain-related parameters, forming a questionnaire with "yes/no" items (decision rules). If at least 10 of the 21 rules applied, persisting pain was predicted at a cross-validated accuracy of 86% and a negative predictive value of approximately 95%.
Conclusions: The present machine-learned analysis showed that, even with a large set of parameters acquired from a large cohort, early identification of these patients is only partly successful. This indicates that more parameters are needed for accurate prediction of persisting pain. However, with the current parameters it is possible, with a certainty of almost 95%, to exclude the possibility of persistent pain developing in a woman being treated for breast cancer.
Wer dem schmalen Band, der eine Art Hinterlassenschaft des 2014 verstorbenen Jacques Le Goff darstellt, gerecht werden möchte, sollte sich zunächst über die Adressaten klar werden: Wie schon häufiger wendet sich der Altmeister der französischen Mediävistik gerade nicht an ein Fachpublikum, sondern an einen weiteren Leserkreis, dem er noch einmal seine Gedanken über ein angemessenes Verständnis von Geschichte und Epochenvorstellungen nahebringen möchte. Wer sich aus wissenschaftlicher Perspektive bereits mit der Frage nach den Konstruktionen des Mittelalters auseinandergesetzt hat oder mit den Arbeiten Le Goffs vertraut ist, erfährt hier wenig grundlegend Neues (so der Autor einleitend selbst, S. 7). Die zentralen Momente und Akteure der "Erfindung" des Mittelalters wurden (mit jüngst steigender Frequenz) bereits intensiv untersucht, und auch Le Goffs Plädoyer für ein "langes Mittelalter" (S. 115–156), das sich bis zum Vorabend der Französischen Revolution erstreckt, ist bekannt. ...
Memory impairments are a major characteristic of schizophrenia (SZ). In the current study, we used an associative memory task to test the hypothesis that SZ patients and first-degree relatives have altered functional patterns in comparison to healthy controls. We analyzed the fMRI activation pattern during the presentation of a face-name task in 27 SZ patients, 23 first-degree relatives, and 27 healthy controls. In addition, we performed correlation analyses between individual psychopathology, accuracy and reaction time of the task and the beta scores of the functional brain activations. We observed a lower response accuracy and increased reaction time during the retrieval of face-name pairs in SZ patients compared with controls. Deficient performance was accompanied by abnormal functional activation patterns predominantly in DMN regions during encoding and retrieval. No significant correlation between individual psychopathology and neuronal activation during encoding or retrieval of face-name pairs was observed. Findings of first-degree relatives indicated slightly different functional pattern within brain networks in contrast to controls without significant differences in the behavioral task. Both the accuracy of memory performance as well as the functional activation pattern during retrieval revealed alterations in SZ patients, and, to a lesser degree, in relatives. The results are of potential relevance for integration within a comprehensive model of memory function in SZ. The development of a neurophysiological model of cognition in psychosis may help to clarify and improve therapeutic options to improve memory and functioning in the illness.
En 2008, le médiéviste Valentin Groebner réfléchissait dans un essai visant un large public sur le rôle du Moyen Âge et de l’histoire médiévale dans les sociétés contemporaines. Selon ses propres dires, cet essai intitulé »Le Moyen Âge ne finit pas«résultait d’une inquiétude devant le décalage croissant, et quelque peu paradoxal, entre l’immense popularité dont cette époque jouit auprès d’un public toujours plus nombreux – »foires médiévales«, romans et films historiques, jeux vidéo – et la marginalisation progressive des études académiques correspondantes (cf. le compte rendu critique de Ludolf Kuchenbuch dans la revue »Rechtsgeschichte – Legal History 20 (2012)«.De fait, et même si ces réflexions ne sont pas entièrement nouvelles, il semble que les publications se multiplient qui traitent de la genèse, du développement et des différents rôles de l’»histoire médiévale«, des différents »Moyen Âges«construits au cours de l’époque moderne ainsi que de la valeur de l’analyse scientifique de cette époque lointaine pour le monde contemporain. Mais faut-il y voir un signe du désarroi des médiévistes, ou plutôt celui d’un renouvellement et repositionnement des études médiévales face aux questions d’aujourd’hui? ...
Numerous cell–cell and cell–matrix interactions within the bone marrow microenvironment enable the controlled lifelong self-renewal and progeny of hematopoietic stem and progenitor cells (HSPCs). On the cellular level, this highly mutual interaction is granted by cell adhesion molecules (CAMs) integrating differentiation, proliferation, and pro-survival signals from the surrounding microenvironment to the inner cell. However, cell–cell and cell–matrix interactions are also critically involved during malignant transformation of hematopoietic stem/progenitor cells. It has become increasingly apparent that leukemia-associated gene products, such as activated tyrosine kinases and fusion proteins resulting from chromosomal translocations, directly regulate the activation status of adhesion molecules, thereby directing the leukemic phenotype. These observations imply that interference with adhesion molecule function represents a promising treatment strategy to target pre-leukemic and leukemic lesions within the bone marrow niche. Focusing on myeloid leukemia, we provide a current overview of the mechanisms by which leukemogenic gene products hijack control of cellular adhesion to subsequently disturb normal hematopoiesis and promote leukemia development.
Die Goethe-Universität will eine Hochschulkultur schaffen, in der Diskriminierung thematisierbar und kritisierbar ist. Diese Broschüre richtet sich an alle Angehörigen der Goethe-Universität. Selbstverständlich sollen sich aber insbesondere Betroffene ermutigt fühlen, sich im Fall von sexualisierter Belästigung an die entsprechenden Beratungspersonen innerhalb und außerhalb der Goethe-Universität zu wenden.
L’intérêt des médiévistes pour les phénomènes d’arbitrage et de résolution des conflits n’est pas nouveau. Il n’est donc pas surprenant que le présent volume, qui réunit les contributions d’un colloque organisé en l’honneur de Hanna Vollrath, fasse explicitement référence à une »étude séminale« qui fut publiée il y a presque trente ans: il s’agit d’une étude de Vollrath sur »Le Moyen Âge dans la typologie des sociétés orales«. L’ensemble des contributions du présent volume confirme la fertilité de ce texte, qui a contribué à déclencher l’analyse des comportements rituels dans la recherche médiévistique allemande qu’elle continue visiblement à inspirer. ...
Background: Human genetic research has implicated functional variants of more than one hundred genes in the modulation of persisting pain. Artificial intelligence and machine‐learning techniques may combine this knowledge with results of genetic research gathered in any context, which permits the identification of the key biological processes involved in chronic sensitization to pain.
Methods: Based on published evidence, a set of 110 genes carrying variants reported to be associated with modulation of the clinical phenotype of persisting pain in eight different clinical settings was submitted to unsupervised machine‐learning aimed at functional clustering. Subsequently, a mathematically supported subset of genes, comprising those most consistently involved in persisting pain, was analysed by means of computational functional genomics in the Gene Ontology knowledgebase.
Results: Clustering of genes with evidence for a modulation of persisting pain elucidated a functionally heterogeneous set. The situation cleared when the focus was narrowed to a genetic modulation consistently observed throughout several clinical settings. On this basis, two groups of biological processes, the immune system and nitric oxide signalling, emerged as major players in sensitization to persisting pain, which is biologically highly plausible and in agreement with other lines of pain research.
Conclusions: The present computational functional genomics‐based approach provided a computational systems‐biology perspective on chronic sensitization to pain. Human genetic control of persisting pain points to the immune system as a source of potential future targets for drugs directed against persisting pain. Contemporary machine‐learned methods provide innovative approaches to knowledge discovery from previous evidence.
Significance: We show that knowledge discovery in genetic databases and contemporary machine‐learned techniques can identify relevant biological processes involved in Persitent pain.
Le présent volume, issu d’un colloque à l’université de Münster en novembre 2009, se situe au carrefour de trois champs thématiques dont aucun ne constitue, en soi, un sujet dont on pourrait prétendre qu’il aurait été jusqu’alors inconnu ou négligé de la recherche scientifique: ni l’amitié, ni le don, ni même la notion de réseaux (sociaux) ne surprennent ainsi dans le contexte des études récentes sur l’histoire sociale et politique du Moyen Âge. C’est la combinaison des trois aspects qui promet l’ouverture de nouvelles pistes. En outre, comme le constate Michael Grünbart dans son introduction (p. XIII–XXV), les approches se concentrant sur les actions ritualisées, qui constituent un courant important au sein des études médiévales, sont moins présentes dans les études byzantinistes. D’où la volonté d’appliquer ces méthodes au monde byzantin dans une perspective comparatiste (p. XIV–XVI). ...
Oxidative stress plays a fundamental role in many conditions. Specifically, redox imbalance inhibits endothelial cell (EC) growth, inducing cell death and senescence. We used global transcriptome profiling to investigate the involvement of noncoding-RNAs in these phenotypes. By RNA-sequencing, transcriptome changes were analyzed in human ECs exposed to H2O2, highlighting a pivotal role of p53-signaling. Bioinformatic analysis and validation in p53-silenced ECs, identified several p53-targets among both mRNAs and long noncoding-RNAs (lncRNAs), including MALAT1 and NEAT1. Among microRNAs (miRNAs), miR-192-5p was the most induced by H2O2 treatment, in a p53-dependent manner. Down-modulated mRNA-targets of miR-192-5p were involved in cell cycle, DNA repair and stress response. Accordingly, miR-192-5p overexpression significantly decreased EC proliferation, inducing cell death. A central role of the p53-pathway was also confirmed by the analysis of differential exon usage: Upon H2O2 treatment, the expression of p53-dependent 5’-isoforms of MDM2 and PVT1 increased selectively. The transcriptomic alterations identified in H2O2-treated ECs were also observed in other physiological and pathological conditions where redox control plays a fundamental role, such as ECs undergoing replicative senescence, skeletal muscles of critical limb-ischemia patients and the peripheral-blood mononuclear cells of long-living individuals. Collectively, these findings indicate a prominent role of noncoding-RNAs in oxidative stress response.