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- 2019
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Tidskriftsartikel (refereegranskat)
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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Blum, Andreas, et al.
(författare)
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Time to diagnosis, of melanoma: same trend in different continents
- 2007
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Ingår i: Journal of Cutaneous Medicine and Surgery. - : SAGE Publications. - 1203-4754 .- 1615-7109. ; 11:4, s. 137-144
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients and physicians both play an important role in the diagnosis of malignant melanoma. Objective: The purpose of this study was to assess important factors of delay in diagnosis at different centers and on three continents. Methods: Between October 2001 and October 2002, patients with histologically confirmed invasive melanoma were included in the study and given an established questionnaire. Recorded patients and tumor characteristics included age, sex, anatomic location, Breslow thickness, patients' awareness of the lesion and time with suspicion, and physicians' time (delay) before the operation. Results: The study included 985 patients (486 males, 499 females): 253 from Germany, 464 from Sweden, 58 from Brazil, and 210 from Australia. More females detected their lesions by themselves. The change to a darker color (21%) and enlargement of the area of the lesion (19%) were the major signs. The highest knowledge among patients that early detection may improve the outcome was found in Sweden and Australia. At each center, the media (newspaper, magazine, radio, and television) provided the best sources of information about melanoma. Twenty to 33% of all physicians initially consulted missed the melanoma diagnosis, independent of their specialty. Conclusions: There are still factors for the delay in melanoma diagnosis in different countries and continents, but the differences are rather small. The results should be included in planning prevention campaigns in this specific field and in the education of medical students, physicians of all specialties, and other health professionals.
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- Haenssle, H A, et al.
(författare)
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Man against machine: diagnostic performance of a deep learning convolutional neural network for dermoscopic melanoma recognition in comparison to 58 dermatologists.
- 2018
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 29:8, s. 1836-1842
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Tidskriftsartikel (refereegranskat)abstract
- Deep learning convolutional neural networks (CNN) may facilitate melanoma detection, but data comparing a CNN's diagnostic performance to larger groups of dermatologists are lacking.Google's Inception v4 CNN architecture was trained and validated using dermoscopic images and corresponding diagnoses. In a comparative cross-sectional reader study a 100-image test-set was used (level-I: dermoscopy only; level-II: dermoscopy plus clinical information and images). Main outcome measures were sensitivity, specificity and area under the curve (AUC) of receiver operating characteristics (ROC) for diagnostic classification (dichotomous) of lesions by the CNN versus an international group of 58 dermatologists during level-I or -II of the reader study. Secondary end points included the dermatologists' diagnostic performance in their management decisions and differences in the diagnostic performance of dermatologists during level-I and -II of the reader study. Additionally, the CNN's performance was compared with the top-five algorithms of the 2016 International Symposium on Biomedical Imaging (ISBI) challenge.In level-I dermatologists achieved a mean (±standard deviation) sensitivity and specificity for lesion classification of 86.6% (±9.3%) and 71.3% (±11.2%), respectively. More clinical information (level-II) improved the sensitivity to 88.9% (±9.6%, P=0.19) and specificity to 75.7% (±11.7%, P<0.05). The CNN ROC curve revealed a higher specificity of 82.5% when compared with dermatologists in level-I (71.3%, P<0.01) and level-II (75.7%, P<0.01) at their sensitivities of 86.6% and 88.9%, respectively. The CNN ROC AUC was greater than the mean ROC area of dermatologists (0.86 versus 0.79, P<0.01). The CNN scored results close to the top three algorithms of the ISBI 2016 challenge.For the first time we compared a CNN's diagnostic performance with a large international group of 58 dermatologists, including 30 experts. Most dermatologists were outperformed by the CNN. Irrespective of any physicians' experience, they may benefit from assistance by a CNN's image classification.This study was registered at the German Clinical Trial Register (DRKS-Study-ID: DRKS00013570; https://www.drks.de/drks_web/).
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- Opitz, Andreas, et al.
(författare)
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Organic heterojunctions : Contact-induced molecular reorientation, interface states, and charge redistribution
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- We reveal the rather complex interplay of contact-induced re-orientation and interfacial electronic structure-in the presence of Fermi-level pinning-at prototypical molecular heterojunctions comprising copper phthalocyanine (H16CuPc) and its perfluorinated analogue (F16CuPc), by employing ultraviolet photoelectron and X-ray absorption spectroscopy. For both layer sequences, we find that Fermi-level (E-F) pinning of the first layer on the conductive polymer substrate modifies the work function encountered by the second layer such that it also becomes E-F-pinned, however, at the interface towards the first molecular layer. This results in a charge transfer accompanied by a sheet charge density at the organic/organic interface. While molecules in the bulk of the films exhibit upright orientation, contact formation at the heterojunction results in an interfacial bilayer with lying and co-facial orientation. This interfacial layer is not EF-pinned, but provides for an additional density of states at the interface that is not present in the bulk. With reliable knowledge of the organic heterojunction's electronic structure we can explain the poor performance of these in photovoltaic cells as well as their valuable function as charge generation layer in electronic devices.
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- Demuth, Andreas, et al.
(författare)
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Pathogenomics: An updated European Research Agenda
- 2008
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Ingår i: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-7257 .- 1567-1348. ; 8:3, s. 386-393
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Tidskriftsartikel (refereegranskat)abstract
- The emerging genomic technologies and bioinformatics provide novel opportunities for studying life-threatening human pathogens and to develop new applications for the improvement of human and animal health and the prevention, treatment, and diagnosis of infections. Based on the ecology and population biology of pathogens and related organisms and their connection to epidemiology, more accurate typing technologies and approaches will lead to better means of disease control. The analysis of the genome plasticity and gene pools of pathogenic bacteria including antigenic diversity and antigenic variation results in more effective vaccines and vaccine implementation programs. The study of newly identified and uncultivated microorganisms enables the identification of new threats. The scrutiny of the metabolism of the pathogen in the host allows the identification of new targets for anti-infectives and therapeutic approaches. The development of modulators of host responses and mediators of host damage will be facilitated by the research on interactions of microbes and hosts, including mechanisms of host damage, acute and chronic relationships as well as commensalisms. The study of multiple pathogenic and non-pathogenic microbes interacting in the host will improve the management of multiple infections and will allow probiotic and prebiotic interventions. Needless to iterate, the application of the results of improved prevention and treatment of infections into clinical tests will have a positive impact on the management of human and animal disease. The Pathogenomics Research Agenda draws on discussions with experts of the Network of Excellence "EuroPathoGenomics" at the management board meeting of the project held during 18-21 April 2007, in the Villa Vigoni, Menaggio, Italy. Based on a proposed European Research Agenda in the field of pathogenomics by the ERA-NET PathoGenoMics the meeting's participants updated the established list of topics as the research agenda for the future.
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| 25. |
- Forsea, Ana-Maria, et al.
(författare)
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Inequalities in the patterns of dermoscopy use and training across Europe : conclusions of the Eurodermoscopy pan-European survey
- 2020
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Ingår i: European journal of dermatology : EJD. - : John Libbey Eurotext. - 1167-1122 .- 1952-4013. ; 30:5, s. 524-531
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dermoscopy is a widely used technique, recommended in clinical practice guidelines worldwide for the early diagnosis of skin cancers. Intra-European disparities are reported for early detection and prognosis of skin cancers, however, no information exists about regional variation in patterns of dermoscopy use across Europe.OBJECTIVE: To evaluate the regional differences in patterns of dermoscopy use and training among European dermatologists.MATERIALS & METHODS: An online survey of European-registered dermatologists regarding dermoscopy training, practice and attitudes was established. Answers from Eastern (EE) versus Western European (WE) countries were compared and their correlation with their respective countries' gross domestic product/capita (GDPc) and total and government health expenditure/capita (THEc and GHEc) was analysed.RESULTS: We received 4,049 responses from 14 WE countries and 3,431 from 18 EE countries. A higher proportion of WE respondents reported dermoscopy use (98% vs. 77%, p<0.001) and training during residency (43% vs. 32%) or anytime (96.5% vs. 87.6%) (p<0.001) compared to EE respondents. The main obstacles in dermoscopy use were poor access to dermoscopy equipment in EE and a lack of confidence in one's skills in WE. GDPc, THEc and GHEc correlated with rate of dermoscopy use and dermoscopy training during residency (Spearman rho: 0.5-0.7, p<0.05), and inversely with availability of dermoscopy equipment.CONCLUSION: The rates and patterns of dermoscopy use vary significantly between Western and Eastern Europe, on a background of economic inequality. Regionally adapted interventions to increase access to dermoscopy equipment and training might enhance the use of this technique towards improving the early detection of skin cancers.
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