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Endothelial to mesenchymal transition in cardiovascular disease : JACC state-of-the-art review
(2019)
Endothelial to mesenchymal transition (EndMT) is a process whereby an endothelial cell undergoes a series of molecular events that lead to a change in phenotype toward a mesenchymal cell (e.g., myofibroblast, smooth muscle cell). EndMT plays a fundamental role during development, and mounting evidence indicates that EndMT is involved in adult cardiovascular diseases (CVDs), including atherosclerosis, pulmonary hypertension, valvular disease, and fibroelastosis. Therefore, the targeting of EndMT may hold therapeutic promise for treating CVD. However, the field faces a number of challenges, including the lack of a precise functional and molecular definition, a lack of understanding of the causative pathological role of EndMT in CVDs (versus being a “bystander-phenomenon”), and a lack of robust human data corroborating the extent and causality of EndMT in adult CVDs. Here, we review this emerging but exciting field, and propose a framework for its systematic advancement at the molecular and translational levels.
Sepsis is characterized by dysregulated gene expression, provoking a hyper-inflammatory response occurring in parallel to a hypo-inflammatory reaction. This is often associated with multi-organ failure, leading to the patient’s death. Therefore, reprogramming of these pro- and anti-inflammatory, as well as immune-response genes which are involved in acute systemic inflammation, is a therapy approach to prevent organ failure and to improve sepsis outcomes. Considering epigenetic, i.e., reversible, modifications of chromatin, not altering the DNA sequence as one tool to adapt the expression profile, inhibition of factors mediating these changes is important. Acetylation of histones by histone acetyltransferases (HATs) and initiating an open-chromatin structure leading to its active transcription is counteracted by histone deacetylases (HDACs). Histone deacetylation triggers a compact nucleosome structure preventing active transcription. Hence, inhibiting the activity of HDACs by specific inhibitors can be used to restore the expression profile of the cells. It can be assumed that HDAC inhibitors will reduce the expression of pro-, as well as anti-inflammatory mediators, which blocks sepsis progression. However, decreased cytokine expression might also be unfavorable, because it can be associated with decreased bacterial clearance.
Big data, data mining, machine learning und predictive analytics – ein konzeptioneller Überblick
(2019)
Mit der fortschreitenden Digitalisierung von Wirtschaft und Gesellschaft wächst die Bedeutung von Big Data Analytics, maschinellem Lernen und Künstlicher Intelligenz für die Analyse und Pognose ökonomischer Trends. Allerdings werden in wirtschaftspolitischen Diskussionen diese Begriffe häufig verwendet, ohne dass jeweils klar zwischen den einzelnen Methoden und Disziplinen differenziert würde. Daher soll nachfolgend ein konzeptioneller Überblick über die Gemeinsamkeiten, Unterschiede und Interdependenzen der vielfältigen Begrifflichkeiten im Bereich Data Science gegeben werden. Denn gerade für Entscheidungsträger aus Wirtschaft und Politik kann eine grundlegende Einordnung der Konzepte eine sachgerechte Diskussion über politische Weichenstellungen erleichtern.
The attention control video has been frequently applied to test the ego depletion effect. However, its validity has never been tested, a shortcoming we address in this preregistered study. In the first task, self-control strength was temporarily depleted in the depletion condition (n = 56) but remained intact in the control condition (n = 56). The attention control video served as the secondary task, and we assumed that the depletion condition would perform significantly worse compared to the control condition. Attention regulation was measured with an eye-tracking device. The results revealed that the gaze behavior in the two conditions differed statistically significantly; however, the actual difference was small, indicating that the attention control video may not be an optimal measure of self-control.
Introduction: The global spread of multidrug-resistant organisms (MDRO) complicates treatment and isolation measures in hospitals and has shown to increase mortality. Patients with disease- or therapy-related immunodeficiency are especially at risk for fatal infections caused by MDRO. The impact of MDRO colonization on the clinical course of AML patients undergoing intensive induction chemotherapy—a potentially curative but highly toxic treatment option—has not been systematically studied.
Materials & methods: 312 AML patients undergoing intensive induction chemotherapy between 2007 and 2015 were examined for MDRO colonization. Patients with evidence for MDRO before or during the hospital stay of induction chemotherapy were defined as colonized, patients who never had a positive swab for MDRO were defined as noncolonized.
Results: Of 312 AML patients 90 were colonized and 130 were noncolonized. Colonized patients suffered from significantly more days with fever, spent more days on the intensive care unit and had a higher median C-reactive protein value during the hospital stay. These findings did not result in a prolonged length of hospital stay or an increased mortality rate for colonized patients. However, in a subgroup analysis, patients colonized with carbapenem-resistant enterobacteriaceae (CRE) had a significantly reduced 60- and 90-day, as well as 1- and 2-year survival rates when compared to noncolonized patients.
Conclusion: Our analysis highlights the importance of intensive MDRO screening especially in patients with febrile neutropenia since persisting fever can be a sign of MDRO-colonization. CRE-colonized patients require special surveillance, since they seem to be at risk for death.
The inhalation of particulate matter (PM) in second-hand smoke (SHS) is hazardous to health of smokers and non-smokers. Tobacco strength (amount of tar, nicotine, and carbon monoxide) and different additives might have an effect on the amount of PM. This study aimed to investigate the influence of tobacco strength or additives on PM. Four cigarette types of the brand Marlboro with different strengths and with or without additives were analyzed in comparison to the 3R4F reference cigarette. SHS was generated by an automatic environmental tobacco smoke emitter (AETSE) in an enclosed space with a volume of 2.88 m³. PM concentrations (PM10, PM2.5, PM1) were measured with a laser aerosol spectrometer followed by statistical analysis. The two strongest Marlboro brands (Red and Red without additives) showed the highest PM concentrations of all tested cigarettes. The measured mean concentrations Cmean of PM10 increased up to 1458 µg/m³ for the Marlboro Red without additives (PM2.5: 1452 µg/m³, PM1: 1263 µg/m³). The similarly strong Marlboro Red showed very similar PM values. The second strongest type Marlboro Gold showed 36% (PM10, PM2.5) and 32% (PM1) lower values, respectively. The “lightest” type Marlboro Silver Blue showed 54% (PM10, PM2.5) or 50% (PM1) lower PM values. The results indicate that the lower the tar, nicotine, and carbon monoxide amounts, as well as the longer the cigarette filter, the lower are the PM levels. An influence of additives could not be determined.
During erythropoiesis, haematopoietic stem cells (HSCs) differentiate in successive steps of commitment and specification to mature erythrocytes. This differentiation process is controlled by transcription factors that establish stage- and cell type-specific gene expression. In this study, we demonstrate that FUSE binding protein 1 (FUBP1), a transcriptional regulator important for HSC self-renewal and survival, is regulated by T-cell acute lymphocytic leukaemia 1 (TAL1) in erythroid progenitor cells. TAL1 directly activates the FUBP1 promoter, leading to increased FUBP1 expression during erythroid differentiation. The binding of TAL1 to the FUBP1 promoter is highly dependent on an intact GATA sequence in a combined E-box/GATA motif. We found that FUBP1 expression is required for efficient erythropoiesis, as FUBP1-deficient progenitor cells were limited in their potential of erythroid differentiation. Thus, the finding of an interconnection between GATA1/TAL1 and FUBP1 reveals a molecular mechanism that is part of the switch from progenitor- to erythrocyte-specific gene expression. In summary, we identified a TAL1/FUBP1 transcriptional relationship, whose physiological function in haematopoiesis is connected to proper erythropoiesis.
Introduction: Epoxyeicosatrienoic acids (EETs) are able to enhance angiogenesis and regulate inflammation that is especially important in wound healing under ischemic conditions. Thus, we evaluated the effect of local EET application on ischemic wounds in mice.
Methods: Ischemia was induced by cautherization of two of the three supplying vessels to the mouse ear. Wounding was performed on the ear three days later. Wounds were treated either with 11,12 or 14,15 EET and compared to untreated control and normal wounds. Epithelialization was measured every second day. VEGF, TNF-α, TGF-β, matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP), Ki67, and SDF-1α were evaluated immunohistochemically in wounds on day 3, 6, and 9.
Results: Ischemia delayed wound closure (12.8 days ± 1.9 standard deviation (SD) for ischemia and 8.0 days ± 0.94 SD for control). 11,12 and14,15 EET application ameliorated deteriorated wound healing on ischemic ears (7.6 ± 1.3 SD for 11,12 EET and 9.2 ± 1.4 SD for 14,15 EET). Ischemia did not change VEGF, TNF-α, TGF-β, SDF-1α, TIMP, MMP7 or MMP9 level significantly compared to control. Local application of 11,12 as well as 14,15 EET induced a significant elevation of VEGF, TGF-β, and SDF-1α expression as well as proliferation during the whole phase of wound healing compared to control and ischemia alone.
Conclusion: In summary, EET improve impaired wound healing caused by ischemia as they enhance neovascularization and alter inflammatory response in wounds. Thus elevating lipid mediator level as 11,12 and 14,15 EET in wounds might be a successful strategy for amelioration of deranged wound healing under ischemia.
Biosynthetic gene content of the "Perfume Lichens" Evernia prunastri and Pseudevernia furfuracea
(2019)
Lichen-forming fungi produce a vast number of unique natural products with a wide variety of biological activities and human uses. Although lichens have remarkable potential in natural product research and industry, the molecular mechanisms underlying the biosynthesis of lichen metabolites are poorly understood. Here we use genome mining and comparative genomics to assess biosynthetic gene clusters and their putative regulators in the genomes of two lichen-forming fungi, which have substantial commercial value in the perfume industry, Evernia prunastri and Pseudevernia furfuracea. We report a total of 80 biosynthetic gene clusters (polyketide synthases (PKS), non-ribosomal peptide synthetases and terpene synthases) in E. prunastri and 51 in P. furfuracea. We present an in-depth comparison of 11 clusters, which show high homology between the two species. A ketosynthase (KS) phylogeny shows that biosynthetic gene clusters from E. prunastri and P. furfuracea are widespread across the Fungi. The phylogeny includes 15 genomes of lichenized fungi and all fungal PKSs with known functions from the MIBiG database. Phylogenetically closely related KS domains predict not only similar PKS architecture but also similar cluster architecture. Our study highlights the untapped biosynthetic richness of lichen-forming fungi, provides new insights into lichen biosynthetic pathways and facilitates heterologous expression of lichen biosynthetic gene clusters.
The current Special Issue is devoted to the broad spectrum of hepatotoxicity with its molecular mechanisms and pathophysiology, presented in eight publications. Scientists were from various countries, including the US, Mexico, the Czech Republic, Germany, Portugal, China, and Japan. Contributions considered various types of experimental and human liver injury, elicited by a number of causal conditions and substances. ...
Background: Hepatitis B (HepB) is a major public health concern in Malaysia yet little is known about knowledge and awareness of this infection in the country. Such information is essential for designing effective intervention strategies for HepB prevention and control. The aim of this study was to characterize knowledge and awareness regarding HepB in Malaysia and to identify their associated sociodemographic determinants.
Methods: A community-based cross-sectional survey was conducted between January and May 2016 in Selangor state of Malaysia. A two-stage cluster random sampling design was used and one adult member of selected households was interviewed face-to-face. Logistic regression was used to estimate the differences in knowledge and awareness between groups.
Results: A total of 764 households completed the interviews and were included in the final analysis. Only 36.9 and 38.8% of the participants had good knowledge and awareness, respectively. The factors associated with good knowledge were being in the 35–44 year age group, Malay ethnicity, high educational attainment and high family income. Being Chinese, being older and having high educational attainment were determinants of having good awareness towards HepB. Participants who had good knowledge were 2.5 times more likely to also have good awareness (OR: 2.41, 95% CI: 1.78–3.26, p < 0.001).
Conclusions: This study reveals a low level of knowledge and awareness of HepB among households in Malaysia. This finding highlights the need to improve public knowledge and awareness through well-designed programs targeting vulnerable groups in order to reduce hepatitis B virus transmission and achieve the governmental target of eliminating viral hepatitis as a public health concern by 2030.
LSTMVoter : chemical named entity recognition using a conglomerate of sequence labeling tools
(2019)
Background: Chemical and biomedical named entity recognition (NER) is an essential preprocessing task in natural language processing. The identification and extraction of named entities from scientific articles is also attracting increasing interest in many scientific disciplines. Locating chemical named entities in the literature is an essential step in chemical text mining pipelines for identifying chemical mentions, their properties, and relations as discussed in the literature. In this work, we describe an approach to the BioCreative V.5 challenge regarding the recognition and classification of chemical named entities. For this purpose, we transform the task of NER into a sequence labeling problem. We present a series of sequence labeling systems that we used, adapted and optimized in our experiments for solving this task. To this end, we experiment with hyperparameter optimization. Finally, we present LSTMVoter, a two-stage application of recurrent neural networks that integrates the optimized sequence labelers from our study into a single ensemble classifier.
Results: We introduce LSTMVoter, a bidirectional long short-term memory (LSTM) tagger that utilizes a conditional random field layer in conjunction with attention-based feature modeling. Our approach explores information about features that is modeled by means of an attention mechanism. LSTMVoter outperforms each extractor integrated by it in a series of experiments. On the BioCreative IV chemical compound and drug name recognition (CHEMDNER) corpus, LSTMVoter achieves an F1-score of 90.04%; on the BioCreative V.5 chemical entity mention in patents corpus, it achieves an F1-score of 89.01%.
Availability and implementation: Data and code are available at https://github.com/texttechnologylab/LSTMVoter.
Adjuvanted influenza vaccines constitute a key element towards inducing neutralizing antibody responses in populations with reduced responsiveness, such as infants and elderly subjects, as well as in devising antigen-sparing strategies. In particular, squalene-containing adjuvants have been observed to induce enhanced antibody responses, as well as having an influence on cross-reactive immunity. To explore the effects of adjuvanted vaccine formulations on antibody response and their relation to protein-specific immunity, we propose different mathematical models of antibody production dynamics in response to influenza vaccination. Data from ferrets immunized with commercial H1N1pdm09 vaccine antigen alone or formulated with different adjuvants was instrumental to adjust model parameters. While the affinity maturation process complexity is abridged, the proposed model is able to recapitulate the essential features of the observed dynamics. Our numerical results suggest that there exists a qualitative shift in protein-specific antibody response, with enhanced production of antibodies targeting the NA protein in adjuvanted versus non-adjuvanted formulations, in conjunction with a protein-independent boost that is over one order of magnitude larger for squalene-containing adjuvants. Furthermore, simulations predict that vaccines formulated with squalene-containing adjuvants are able to induce sustained antibody titers in a robust way, with little impact of the time interval between immunizations.
Background: Arthropod-borne diseases remain a major health-threat for humans and animals worldwide. To estimate the distribution of pathogenic agents and especially Bartonella spp., we conducted tick microbiome analysis and determination of the infection status of wild animals, pets and pet owners in the state of Hesse, Germany.
Results: In total, 189 engorged ticks collected from 163 animals were tested. Selected ticks were analyzed by next generation sequencing (NGS) and confirmatory PCRs, blood specimens of 48 wild animals were analyzed by PCR to confirm pathogen presence and sera of 54 dogs, one cat and 11 dog owners were analyzed by serology. Bartonella spp. were detected in 9.5% of all ticks and in the blood of 17 roe deer. Further data reveal the presence of the human and animal pathogenic species of genera in the family Spirochaetaceae (including Borrelia miyamotoi and Borrelia garinii), Bartonella spp. (mainly Bartonella schoenbuchensis), Rickettsia helvetica, Francisella tularensis and Anaplasma phagocytophilum in ticks. Co-infections with species of several genera were detected in nine ticks. One dog and five dog owners were seropositive for anti-Bartonella henselae-antibodies and one dog had antibodies against Rickettsia conorii.
Conclusions: This study provides a snapshot of pathogens circulating in ticks in central Germany. A broad range of tick-borne pathogens are present in ticks, and especially in wild animals, with possible implications for animal and human health. However, a low incidence of Bartonella spp., especially Bartonella henselae, was detected. The high number of various detected pathogens suggests that ticks might serve as an excellent sentinel to detect and monitor zoonotic human pathogens.
Purpose: To examine whether applying case management in general practices reduces thromboembolic events requiring hospitalization and major bleeding events (combined primary outcome). Secondary endpoints were mortality, frequency and duration of hospitalization, severe treatment interactions, adverse events, quality of anticoagulation, health-related quality of life and intervention costs, patients’ assessment of chronic illness care, self-reported adherence to medication, GP and HCA knowledge, patient knowledge and satisfaction with shared decision-making.
Methods: Cluster-randomized controlled trial undertaken at 52 general practices in Germany with adult patients with a long-term indication for oral anticoagulation. The complex intervention included training for healthcare assistants, information and quality circles for general practitioners and 24 months of case management for patients. Assessment was after 12 and 24 months. The intention-to-treat population included all randomized practices and patients, while the per-protocol analysis included only those that received treatment without major protocol violations.
Results: The mean (SD) age of the 736 patients was 73.5 (9.4) years and 597 (81.1%) had atrial fibrillation. After 24 months, the primary endpoint had occurred in 40 (11.0%) intervention and 48 (12.9%) control patients (hazard ratio 0.83, 95% CI 0.55 to 1.25; P = .37). Patients’ perceived quality of care, their knowledge, and HCAs’ knowledge, had improved significantly at 24 months. The other secondary endpoints did not differ between groups. In the intervention group, hospital admissions were significantly reduced in patients that received treatment without major protocol deviations.
Conclusions: Even though the main outcomes did not differ significantly, the intervention appears to have positively influenced several process parameters under "real-world conditions".
Hier werden bemerkenswerte floristische Funde aus Nordrhein-Westfalen aus dem Jahr 2018 und einige Nachträge aus 2017 zusammengestellt, die aus Sicht der Schriftleitung von landesweiter Bedeutung sind. Die Funde werden im Laufe des Jahres zunächst chronologisch auf die Homepage des Bochumer Botanischen Vereins gestellt und am Ende des Jahres zu einem Artikel zusammengefasst. Bei der Auswahl der Arten für diese Liste ist in der Regel nicht an Bestätigung bereits lange bekannter Vorkommen gedacht, die an Ort und Stelle durchgehend vorkommen, sondern z. B. an Neufunde seltener Arten, Wieder-funde seltener Arten, die zwischendurch verschwunden schienen (wie z. B. Acker-unkräuter) oder auch an bekannte Vorkommen, die erloschen sind oder kurz vor dem Erlöschen stehen. Außerdem nehmen Beobachtungen von neophytischen Arten einen großen Raum ein, die entweder auf dem Wege der Einbürgerung sind, deren Einbürgerung noch nicht allgemein bekannt bzw. anerkannt ist oder deren Vorkommen bisher erst selten für Nordrhein-Westfalen veröffentlicht wurden. Ein wichtiges Kriterium für aufgeführte Arten ist die Seltenheit im Bundesland oder in der betreffenden Großlandschaft bzw. Region. Die Zuordnung der Arten zu Pflanzenfamilien richtet sich nach PAROLLY & ROHWER 2016.
In Aachen konnten an zwei Stellen naturverjüngte Populationen von Corylus ×colurnoides, der Hybride zwischen der heimischen Hasel, C. avellana, und der oft gepflanzten, in Aachen tendenziell etablierten Baum-Hasel, C. colurna, festgestellt werden. Sie wachsen im Siedlungsbereich an Straßen und auf einem Friedhof. Hybrid-pflanzen zeigen morphologisch eine große Spanne zwischen den Eltern. Ihre Merkmale und die der Eltern werden ausführlich beschrieben und abgebildet. Ebenso werden Ökologie und Vorkommen der Elternarten in Aachen kurz angerissen. Die Entstehung der Hybridpopulationen wird diskutiert. Wahrscheinlich sind Hybridpopulationen unter Beteiligung gepflanzter Hybriden entstanden.
Weit ab von dem einzigen bekannten nordrhein-westfälischen Kleinareal von Ochlopoa supina im Hochsauerland konnte ein Bestand der Art in kolliner Lage in einem Scherrasen und einem Gebüschsaum in Aachen gefunden werden. Ebenfalls nachgewiesen werden konnte eine Pflanze von O. ×nannfeldtii s. l., der Hybride von O. supina mit O. annua s. l. Die Merkmale von O. supina, O. annua s. str. und O. ×nannfeldtii s. l. in Aachen werden ausführlich dargestellt, abgebildet und diskutiert.
Merkmale und Ökologie der im Aachener Stadtgebiet und angrenzenden Gebieten häufigen, nah verwandten Moose Streblotrichum commutatum (= Barbula commutata JUR. = B. sardoa (SCHIMP.) J.-P. FRAHM) und S. convolutum s. str. (= B. convoluta s. str.) werden vorgestellt. Durch stabile Merkmale wie Größe, Habitus, Blattform und -farbe sind sie meist problemlos zu unterscheiden und behalten bei Kultur unter gleichen Bedingungen ihre Unterschiede bei. Ökologisch sind sie im Untersuchungsgebiet euryök bei überlappenden, schwerpunktmäßig aber getrennten Standortbedingungen. S. commutatum wächst hauptsächlich auf Mauern und frischem Schotter sowie auf offenen, meist lehmigen Böden. Die Art hat dabei Pioniercharakter. Weniger belichtete, basenreiche Standorte werden bevorzugt, sind aber nicht notwendig. Demgegenüber zieht S. convolutum eher stabilere Standortbedingungen vor und bildet typischerweise gemeinsam mit anderen Arten geschlossene Moosrasen besonders auf älteren Wegen und übererdetem Teer. Offene bis halbschattige, somit recht lichtreiche Standorte werden bevorzugt. Literaturangaben zur Ökologie von S. commutatum und S. convolutum aus anderen Regionen werden diskutiert. Dabei stellt sich heraus, dass S. commutatum im Untersuchungsgebiet eine breitere Standortpalette besiedelt als für andere Regionen angegeben und anderswo beobachtete ökologische Unterschiede im Untersuchungsgebiet oft nicht oder nur tendenziell zutreffen.
Auf dem Gelände des Dortmunder Flughafens kommen an zwei Stellen Populationen der Knabenkraut-Hybride Dactylorhiza maculata agg. × D. majalis vor: an einer parallel zur Rollbahn verlaufenden nordexponierten Böschung und in der Dachbegrünung neben der Besucherterrasse des Flughafengebäudes. Die Flächen werden von den Flughafenmitarbeitern gepflegt, wodurch ein dauerhafter Schutz der Orchideen-Vorkommen gewähr-leistet ist. Morphologie und Zeichnungen der Blüten und Blätter der Hybriden werden genau beschrieben, ihre Wuchsorte und die Populationsentwicklung an den Wuchsorten geschildert. Auf dem Gelände konnte außerdem eine Reihe von interessanten Pflanzenarten gefunden werden, die auf der Roten Liste stehen. Sie stammen z. T. aus Ansaaten und haben sich durch geeignete Pflegemaßnahmen in Wiesen eingebürgert.