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  • 1
    In: BMC Complementary and Alternative Medicine, Springer Science and Business Media LLC, Vol. 17, No. S1 ( 2017-6)
    Type of Medium: Online Resource
    ISSN: 1472-6882
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
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  • 2
    In: Research Ideas and Outcomes, Pensoft Publishers, Vol. 8 ( 2022-10-12)
    Abstract: The Helmholtz Association (Anonymous 2022d), the largest association of large-scale research centres in Germany, covers a wide range of research fields employing more than 43.000 researchers. In 2019, the Helmholtz Metadata Collaboration (HMC) (Anonymous 2022f) Platform as a joint endeavor across all research areas of the Helmholtz Association was started to make the depth and breadth of research data produced by Helmholtz Centres findable, accessible, interoperable, and reusable (FAIR) for the whole science community. To reach this goal, the concept of FAIR Digital Objects (FAIR DOs) has been chosen as top-level commonality for existing and future infrastructures of all research fields. In doing so, HMC follows the original approach of realizing FAIR DOs based on globally unique, Persistent Identifiers (PID), e.g., provided by https://handle.net/, machine actionable PID Records and strong typing using Data Types like https://dtr-test.pidconsortium.eu/#objects/21.T11148/1c699a5d1b4ad3ba4956 registered in a Data Type Registry, e.g., http://dtr-test.pidconsortium.eu/. In all these areas, HMC can build on the great groundwork of the Research Data Alliance and the FAIR DO Forum. However, when it comes to realization, there are still some gaps that will have to be addressed during our work and will be raised in this presentation. For single FAIR DO components like PIDs and Data Types, existing infrastructures are already available. Here, the Gesellschaft für wissenschaftliche Datenverarbeitung mbH Göttingen (GWDG) (Anonymous 2022e) provides strong support with their many years of experience in this field. Within the framework of the ePIC consortium (Anonymous 2022c), the GWDG is offering on the one hand PID prefixes based on a sustainable business model, on the other hand GWDG is very active in terms of providing base services required for realizing FAIR DOs, e.g., different instances of Data Type Registries for accessing, creating, and managing Data Types required by FAIR DOs. Besides that, in the context of HMC we developed a couple of technical components to support the creation and management of FAIR DOs: The Typed PID Maker (Pfeil 2022b) providing machine actionable interfaces for creating, validating, and managing PIDs with machine-actionable metadata stored in their PID record, or the FAIR DO testbed, currently evolving into the FAIR DO Lab (Pfeil 2022a), serving as reference implementation for setting up a FAIR DO ecosystem. However, introducing FAIR DOs is not only about providing technical services, but also requires the definition and agreement on interfaces, policies, and processes. A first step in this direction was made in the context of HMC by agreeing on a Helmholtz Kernel Information Profile (http://dtr-test.pidconsortium.eu/#objects/21.T11148/b9b76f887845e32d29f7). In the concept of FAIR DOs, PID Kernel Information as defined by Weigel et al. (Weigel et al. 2018) is key to machine actionability of digital content. Strongly relying on Data Types and stored in the PID record directly at the PID resolution service, PID Kernel Information can be used by machines for fast decision making. The Helmholtz Kernel Information Profile is an attempt to introduce a top-level commonality across all digital assets produced within the Helmholtz Association and beyond to establish a basis for FAIR research data based on FAIR DOs. Hereby, the Helmholtz Kernel Information Profile integrates the recommendations of the RDA PID Kernel Information Working Group (Anonymous 2022b) as far as possible. By extending the Draft Kernel Information Profile (Weigel et al. 2018) with additional, mostly optional attributes, the Helmholtz Kernel Information Profile allows the adding of contextual information to FAIR DOs, e.g., research topic, or contact information, which is then available for machine decisions. Furthermore, additional properties for representing relationships between FAIR DOs, e.g, hasMetadata and isMetadataFor, were introduced to allow mutual relations between FAIR DOs. Currently, a demonstrator is implemented integrating the above components and services, i.e., PID Service, Data Type Registry, and Typed PID Maker. Fig. 1 outlines the architecture overview of the first version of the demonstrator. In this first version, in a semi-automatic workflow, a user enters a Zenodo (Anonymous 2022a) PID in a graphical Web frontend. A mapping component tries to fill automatically at least the properties required by the Helmholtz Kernel Information Profile using the obtained Zenodo metadata record. In a manual validation loop, the user may add or update certain properties before they are sent to an instance of the Typed PID Maker, validated against the Helmholtz Kernel Information Profile, and stored in the record of a newly registered PID using the services of the ePIC consortium. In addition, registered PID records are made searchable via the graphical frontend on top of a search index, e.g., realized using https://www.elastic.co/. After implementing this generic workflow, additional mappers supporting other repository platforms will be implemented based on the lessons learned, which will lead to a growing number of FAIR DOs and holds potential for providing significant benefits to scientists, e.g., a central point of contact for research data sets stored in different repositories, machine-actionable identification of relevant datasets, and creation of knowledge graphs representing relationships between data sets, repository platforms, researchers and research organizations. Furthermore, the gathered experience and its documentation will help others to apply the FAIR DO concept more easily, which will lead to an ever-growing collection of available FAIR DOs with an increasing quality and level of automation at creation time.
    Type of Medium: Online Resource
    ISSN: 2367-7163
    Language: Unknown
    Publisher: Pensoft Publishers
    Publication Date: 2022
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  • 3
    In: Autophagy, Informa UK Limited, Vol. 17, No. 1 ( 2021-01-02), p. 1-382
    Type of Medium: Online Resource
    ISSN: 1554-8627 , 1554-8635
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2262043-6
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  • 4
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 17, No. 1 ( 2023-01-26), p. 37-48
    Abstract: There are concerns regarding the potential impact of the COVID-19 outbreak on patients with inflammatory bowel disease [IBD]. We report on the impact of the COVID-19 outbreak in a European prospective cohort study of patients with IBD Patients and Methods We prospectively collected data from 5457 patients with IBD nested in the ongoing I-CARE project and still followed up in April 2020, with monthly online monitoring of clinical activity, treatment, imaging and endoscopy. Investigators were also contacted to report incidental cases. Results In total, 233 [4.3%] reported COVID-19 and 12 [0.2%] severe COVID-19, with no COVID-19 deaths. The risk of COVID-19 in patients with IBD was not increased compared to the general population (standardized incidence ratio [SIR]: 1.18, 95% confidence interval [CI] [1.03–1.34], p = 0.009), as well as the risk of severe COVID-19 (SIR: 0.69, 95% CI [0.35–1.20] , p = 0.93). We did not observe any negative impact of the different IBD-related medication on the risk of either COVID-19 or severe COVID-19. In 2020, the COVID-19 outbreak resulted in a drastic decrease in endoscopic and imaging procedures from March to May 2020 compared to 2018 and 2019. No impacts on clinical IBD disease activity as well as ongoing treatment were noted. Conclusion No increases in either COVID-19 or severe COVID-19 incidences were observed in patients with IBD. There was no impact of COVID-19 on IBD-related medication and clinical activity. Access to endoscopy and imaging was restricted during the first months of the first COVID-19 outbreak.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 5
    In: Annals of Intensive Care, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-12)
    Abstract: Acute respiratory distress syndrome (ARDS) is a life-threatening condition that often requires prolonged mechanical ventilation. Tracheostomy is a common procedure with some risks, on the other hand with potential advantages over orotracheal intubation in critically ill patients. This study investigated the association of tracheostomy with health-related quality of life (HRQoL), symptoms of psychiatric disorders and return-to-work of ARDS survivors. Methods Data were collected in the context of the prospective observational German-wide DACAPO study. Clinical and demographic patient data and treatment characteristics were obtained from the participating intensive care units (ICU). HRQoL and return-to-work were assessed using patient-reported questionnaires 3, 6 and 12 months after ICU discharge. HRQoL was measured with the Physical and Mental Component Scale of the Short-Form 12 Questionnaire (PCS-12, MCS-12). The prevalence of psychiatric symptoms (depression and post-traumatic stress disorder [PTSD]) was assessed using the Patient Health Questionnaire-9 and the Post-Traumatic Stress Syndrome-14. Physician-diagnosed anxiety and obsessive–compulsive disorder were recorded by patient self-report in the follow-up questionnaires. The associations of tracheostomy with HRQoL, psychiatric symptoms and return-to-work after 12 months were investigated by means of multivariable linear and logistic regression models. Results Primary 877 ARDS patients (mean ± standard deviation: 54 ± 16 years, 68% male) survived and were discharged from ICU. Out of these patients, 478 (54.5%) were tracheotomised during ICU treatment. After 12 months, patient-reported outcomes could be analysed of 388 (44.2%) respondents, 205 with tracheostomy and 183 without. One year after ICU discharge, tracheostomy showed no significant association with physical or mental health-related quality of life (PCS-12: − 0.73 [− 3.96, 2.51]; MCS-12: − 0.71 [− 4.92, 3.49] ), symptoms of psychiatric disorders (depression: 0.10 [− 1.43, 1.64]; PTSD: 3.31 [− 1.81, 8.43] ; anxiety: 1.26 [0.41, 3.86]; obsessive–compulsive disorder: 0.59 [0.05, 6.68] ) or return-to-work (0.71 [0.31, 1.64]) in the multivariable analysis (OR [95%-CI] ). Conclusions Up to 1 year after ICU discharge, neither HRQoL nor symptoms of psychiatric disorders nor return-to-work was affected by tracheostomy. Trial registration NCT02637011 (ClinicalTrials.gov, Registered 15 December 2015, retrospectively registered)
    Type of Medium: Online Resource
    ISSN: 2110-5820
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
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  • 6
    In: Nature, Springer Science and Business Media LLC, Vol. 600, No. 7889 ( 2021-12-16), p. 472-477
    Abstract: The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 7
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2012
    In:  Neuro-Oncology Vol. 14, No. suppl 3 ( 2012-09-01), p. iii1-iii94
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 14, No. suppl 3 ( 2012-09-01), p. iii1-iii94
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2012
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  • 8
    In: Nature, Springer Science and Business Media LLC, Vol. 592, No. 7854 ( 2021-04-15), p. 450-456
    Abstract: Hepatocellular carcinoma (HCC) can have viral or non-viral causes 1–5 . Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need 6,7 . Here we report the progressive accumulation of exhausted, unconventionally activated CD8 + PD1 + T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8 + PD1 + T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH–HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8 + PD1 + CXCR6 + , TOX + , and TNF + T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8 + T cells or TNF neutralization, suggesting that CD8 + T cells help to induce NASH–HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8 + PD1 + T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH–HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 9
    In: Database, Oxford University Press (OUP), Vol. 2019 ( 2019-01-01)
    Abstract: Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.
    Type of Medium: Online Resource
    ISSN: 1758-0463
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 10
    In: Molecular & Cellular Proteomics, Elsevier BV, Vol. 17, No. 12 ( 2018-12), p. 2534-2545
    Type of Medium: Online Resource
    ISSN: 1535-9476
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2071375-7
    SSG: 12
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