Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of ...therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy. The most common and aggressive subgroup, posterior fossa ependymoma group A (PF-EPN-A), occurs in young children and appears to lack recurrent somatic mutations. Conversely, posterior fossa ependymoma group B (PF-EPN-B) tumours display frequent large-scale copy number gains and losses but have favourable clinical outcomes. More than 70% of supratentorial ependymomas are defined by highly recurrent gene fusions in the NF-κB subunit gene RELA (ST-EPN-RELA), and a smaller number involve fusion of the gene encoding the transcriptional activator YAP1 (ST-EPN-YAP1). Subependymomas, a distinct histologic variant, can also be found within the supratetorial and posterior fossa compartments, and account for the majority of tumours in the molecular subgroups ST-EPN-SE and PF-EPN-SE. Here we describe mapping of active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts, with the goal of identifying essential super-enhancer-associated genes on which tumour cells depend. Enhancer regions revealed putative oncogenes, molecular targets and pathways; inhibition of these targets with small molecule inhibitors or short hairpin RNA diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymomas. Through profiling of transcriptional enhancers, our study provides a framework for target and drug discovery in other cancers that lack known genetic drivers and are therefore difficult to treat.
ObjectiveTo identify factors and assess to what extent they impact the magnitude of the treatment effect of acupuncture therapies across therapeutic areas.Data sourceMedline, Embase, Cochrane Central ...Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc, between 2015 and 2019.Study selectionThe inclusion criteria were trials with a total number of randomised patients larger than 100, at least one patient-important outcome and one of two sets of comparisons.Data analysisThe potential independent variables were identified by reviewing relevant literature and consulting with experts. We conducted meta-regression analyses with standardised mean difference (SMD) as effect estimate for the dependent variable. The analyses included univariable meta-regression and multivariable meta-regression using a three-level robust mixed model.Results1304 effect estimates from 584 acupuncture randomised controlled trials (RCTs) were analysed. The multivariable analyses contained 15 independent variables . In the multivariable analysis, the following produced larger treatment effects of large magnitude (>0.4): quality of life (difference of adjusted SMDs 0.51, 95% CI 0.24 to 0.77), or pain (0.48, 95% CI 0.27 to 0.69), or function (0.41, 95% CI 0.21 to 0.61) vs major events. The following produced larger treatment effects of moderate magnitude (0.2–0.4): single-centred vs multicentred RCTs (0.38, 95% CI 0.10 to 0.66); penetration acupuncture vs non-penetration types of acupuncture (0.34, 95% CI 0.15 to 0.53); non-pain symptoms vs major events (0.32, 95% CI 0.12 to 0.52). The following produced larger treatment effects of small magnitude (<0.2): high vs low frequency treatment sessions (0.19, 95% CI 0.03 to 0.35); pain vs non-pain symptoms (0.16, 95% CI 0.04 to 0.27); unreported vs reported funding (0.12, 95% CI 0 to 0.25).ConclusionPatients, clinicians and policy-makers should consider penetrating over non-penetrating acupuncture and more frequent treatment sessions when feasible and acceptable. When designing future acupuncture RCTs, trialists should consider factors that impact acupuncture treatment effects.
Conventional in vitro propagation may affect normal morphophysiological characteristics and survival during the acclimatization of commercial plants, such as
Etlingera Elatior
(Jack) R.M. Smith. CO
2
...enrichment, gas-permeable membranes, and reduced carbohydrate concentration in culture media can be used to mitigate these effects. Here, we aimed to determine the impact of photomixotrophic and photoautotrophic growth on morphophysiological responses of
E. elatior
and its survival during ex vitro acclimatization. In vitro-established plants were placed in flasks containing semisolid MS medium with 0.54 µM α-naphthalene acetic acid and sucrose (0 or 15 g L
−1
). The flasks were sealed with lids with or without orifices covered by gas-permeable membranes and kept for 45 days under forced-air ventilation (360 or 1000 µmol
−1
CO
2
). Growth variables, anatomical and physiological characteristics, and survival rate were evaluated. Overall, 1000 µmol mol
−1
CO
2
, gas-permeable membranes, and 15 g L
−1
sucrose resulted in plants with higher fresh and dry mass, higher level of photosynthetic pigments, as well as more developed secondary ribs in the leaves, prominent midribs, highly organized and differentiated chlorenchyma cells (palisade and spongy parenchyma), more developed vascular bundles, and intercellular gaps were reduced, compared to conventionally in vitro-propagated plants. Moreover, these conditions promote morphophysiological responses and favored survival of
E. elatior
plants (75%) when transferred to ex vitro conditions.
Media didactics Witt, Claudia de; Czerwionka, Thomas
2007
Web Resource
Odprti dostop
How can media support teaching and learning processes? The text of the study offers a systematic introduction to the basics of media didactics and provides the knowledge needed to design media-based ...training courses. The authors provide a compact overview from media-pedagogical approaches to current trends in e-learning (“WIKIS” and “Podcast”). The handout for all, the media reflects on the use of teaching-learning processes.
Wie können Medien Lehr- und Lernprozesse unterstützen? Der Studientext gibt einen systematischen Einstieg in die Grundlagen der Mediendidaktik und vermittelt Handlungswissen, das zur Gestaltung medienbasierter Weiterbildungsangebote benötigt wird. Die Autoren liefern einen kompakten Überblick von den medienpädagogischen Ansätzen bis hin zu gegenwärtigen Trends des E-Learnings ("WIKIS" und "Podcast"). Die Handreichung für alle, die Medien reflektiert in Lehr-Lern-Prozessen einsetzen.
Two novel genomes comprising ≈4.9 kb were identified by next-generation sequencing from pooled organs of Tadarida brasiliensis bats. The overall nucleotide sequence identities between the viral ...genomes characterized here were less than 80 % in comparison to other polyomaviruses (PyVs), members of the family Polyomaviridae. The new genomes display the archetypal organization of PyVs, which includes open reading frames for the regulatory proteins small T antigen (STAg) and large T antigen (LTAg), as well as capsid proteins VP1, VP2 and VP3. In addition, an alternate ORF was identified in the early genome region that is conserved in a large monophyletic group of polyomaviruses. Phylogenetic analysis showed similar clustering with group of PyVs detected in Otomops and Chaerephon bats and some species of monkeys. In this study, the genomes of two novel PyVs were detected in bats of a single species, demonstrating that these mammals can harbor genetically diverse polyomaviruses.
Several studies regarding superficial treatments of Nitinol (NiTi) shape-memory have been developed aiming to the improve corrosion resistance and to block the Ni release to adjacent tissues. The ...necessary heat treatment to achieve the shape memory effect normally occurs at temperatures between 500 and 600 degreesC. However, titanium oxide (TiO sub(2)) is formed on the NiTi surface during the shape memory process heat treatment. In this work the effects of the heat treatment time on the surface characteristics of the formed NiTi oxide, at temperatures that promote the shape-memory (530 and 570 degreesC), were evaluated. The TiO sub(2) layers which were obtained were evaluated by X-ray diffraction (XRD), energy dispersive X-ray (EDX), scanning electron microscope (SEM), thermogravimetric analysis (TGA), wettability and roughness. The results show that by increasing the exposure time at the temperature of 570 degreesC the formation of a thicker oxide is promoted, with less superficial roughness and of a hydrophobic nature. According to the literature, these characteristics indicate that the obtained oxide layer has properties that accelerat the osseointegration process.
Traditional Chinese medicine (TCM) is an integral part of mainstream medicine in China. Due to its worldwide use, potential impact on healthcare and opportunities for new drug development, TCM is ...also of great international interest. Recently, a new era for modernisation of TCM was launched with the successful completion of the Good Practice in Traditional Chinese Medicine Research in the Post-genomic Era (GP-TCM) project, the European Union's Seventh Framework Programme (FP7) coordination action on TCM research. This 3.5-year project that involved inputs from over 200 scientists resulted in the production of 20 editorials and in-depth reviews on different aspects of TCM that were published in a special issue of Journal of Ethnopharmacology (2012; volume 140, issue 3). In this narrative review, we aim to summarise the findings of the FP7 GP-TCM project and highlight the relevance of TCM to modern medicine within a historical and international context. Advances in TCM research since the 1950s can be characterised into three phases: Phase I (1950s-1970s) was fundamental for developing TCM higher education, research and hospital networks in China; Phase II (1980s-2000s) was critical for developing legal, economic and scientific foundations and international networks for TCM; and Phase III (2011 onwards) is concentrating on consolidating the scientific basis and clinical practice of TCM through interdisciplinary, interregional and intersectoral collaborations. Taking into account the quality and safety requirements newly imposed by a globalised market, we especially highlight the scientific evidence behind TCM, update the most important milestones and pitfalls, and propose integrity, integration and innovation as key principles for further modernisation of TCM. These principles will serve as foundations for further research and development of TCM, and for its future integration into tomorrow's medicine.
Rabies surveillance in wild mammals in South of Brazil Campos, Aline Alves Scarpellini; Santos, Raíssa Nunes; Benavides, Julio A. ...
Transboundary and emerging diseases,
March 2020, 2020-Mar, 2020-03-00, 20200301, Letnik:
67, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The sylvatic cycle of rabies, caused by the Rabies lyssavirus (RABV), is maintained in the American Continent by aerial and terrestrial wild mammals. In this study, we combined passive surveillance ...of rescued wild animals with active serological surveillance in targeting areas at Rio Grande do Sul State and Santa Catarina State, south of Brazil, where bites of humans by wild animals have been reported. Circulation of RABV in Brazilian bats has been extensively demonstrated; however, the observation of such infections in unvaccinated terrestrial mammals is restricted to some regions of the Brazilian territory. The occurrence of rabies infection in unvaccinated animals has been identified by the detection of RABV antigens in brain tissues of dead animals or anti‐rabies antibodies in live animals. Such strategies allow the surveillance of rabies and the assessment of spillover risks from infected animals to humans. Our aim included the identification of species of wild mammals that are involved in the sylvatic cycle of rabies virus in Southern Brazil and to assess the risk of rabies infection in patients bitten by wild animals in the state. To assess the anti‐rabies seropositivity, sera were submitted to the Rapid Fluorescent Focus Inhibition Test (RFFIT). Among the 100 mammals tested, five animals were seropositive (5%) including three (one primate and two wild canids) with rabies virus neutralizing antibodies titres >0.5 IU/ml. Our results highlight the exposure to RABV of both primates and wild canids in Southern Brazil and suggest the occurrence of RABV exposure without the development of further symptoms. Further research should clarify the dynamics of rabies in wild canids and whether primates are accidental hosts or reservoirs for RABV at this region.
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