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  1. Book ; Thesis: Beeinflussung von N 2-Fixierung und Pflanzenwachstum durch arbuskuläre Mykorrhiza bei Erbse (Pisum sativum L.)

    Reinhard, Stefan

    1995  

    Author's details Stefan Reinhard
    Keywords Erbse ; Stickstofffixierung ; Wachstum ; VA-Mykorrhiza
    Subject Vesikulär-arbuskuläre Mykorrhiza ; Arbuskuläre Endomykorrhiza ; VAM ; Arbuskuläre Mykorrhiza ; Stickstoffbindung ; Stickstoff-Fixierung ; Stickstoffixierung ; N-Fixierung ; Saaterbse ; Pisum sativum
    Size 115 S. : graph. Darst.
    Publisher Grauer
    Publishing place Stuttgart
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Hohenheim, Univ., Diss., 1995
    Remark AY 17472 ; Abt. Nussallee/Bereichsbibl. ZBMed: AY 17472
    HBZ-ID HT006828296
    ISBN 3-86186-093-7 ; 978-3-86186-093-8
    Database Catalogue ZB MED Nutrition, Environment, Agriculture

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  2. Book ; Thesis: Vergleich von pulsatilem und kontinuierlichem Perfusionsverfahren während extrakorporaler Zirkulation bei aortokoronaren Bypass-Operationen

    Bulling, Reinhard Stefan

    1998  

    Author's details vorgelegt von Reinhard Stefan Bulling
    Language German
    Size IV, 102 S. : graph. Darst.
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Gießen, Univ., Diss., 1999
    HBZ-ID HT012848028
    Database Catalogue ZB MED Medicine, Health

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  3. Book ; Online ; Thesis: Control of primate prehension in space and time

    Greulich, Reinhard Stefan [Verfasser]

    2021  

    Author's details Reinhard Stefan Greulich
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language English
    Publisher Niedersächsische Staats- und Universitätsbibliothek Göttingen
    Publishing place Göttingen
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  4. Article ; Online: Systematic Investigation of SARS-CoV-2 Receptor Protein Distribution along Viral Entry Routes in Humans.

    Bräutigam, Konstantin / Reinhard, Stefan / Galván, José A / Wartenberg, Martin / Hewer, Ekkehard / Schürch, Christian M

    Respiration; international review of thoracic diseases

    2022  Volume 101, Issue 6, Page(s) 610–618

    Abstract: Background: The novel beta-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters the human body via mucosal surfaces of the upper and/or lower respiratory tract. Viral entry into epithelial cells is mediated via angiotensin- ... ...

    Abstract Background: The novel beta-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters the human body via mucosal surfaces of the upper and/or lower respiratory tract. Viral entry into epithelial cells is mediated via angiotensin-converting enzyme 2 (ACE2) and auxiliary molecules, but the precise anatomic site of infection still remains unclear.
    Methods: Here, we systematically investigated the main SARS-CoV-2 receptor proteins ACE2 and transmembrane serine protease 2 (TMPRSS2), as well as 2 molecules potentially involved in viral entry, furin and CD147, in formalin-fixed, paraffin-embedded human tissues. Tissue microarrays incorporating a total of 879 tissue cores from conjunctival (n = 84), sinonasal (n = 95), and lung (bronchiolar/alveolar; n = 96) specimens were investigated for protein expression by immunohistochemistry.
    Results: ACE2 and TMPRSS2 were expressed in ciliated epithelial cells of the conjunctivae and sinonasal tissues, with highest expression levels observed in the apical cilia. In contrast, in the lung, the expression of those molecules in bronchiolar and alveolar epithelial cells was much rarer and only very focal when present. Furin and CD147 were more uniformly expressed in all tissues analyzed, including the lung. Interestingly, alveolar macrophages consistently expressed high levels of all 4 molecules investigated.
    Conclusions: Our study confirms and extends previous findings and contributes to a better understanding of potential SARS-CoV-2 infection sites along the human respiratory tract.
    MeSH term(s) Angiotensin-Converting Enzyme 2/metabolism ; Basigin/metabolism ; COVID-19/metabolism ; COVID-19/virology ; Furin/metabolism ; Humans ; Lung/metabolism ; Respiratory System/metabolism ; Respiratory System/virology ; SARS-CoV-2 ; Serine Endopeptidases/metabolism ; Virus Internalization
    Chemical Substances BSG protein, human ; Basigin (136894-56-9) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-) ; FURIN protein, human (EC 3.4.21.75) ; Furin (EC 3.4.21.75)
    Language English
    Publishing date 2022-01-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 206674-9
    ISSN 1423-0356 ; 0025-7931
    ISSN (online) 1423-0356
    ISSN 0025-7931
    DOI 10.1159/000521317
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Evaluation of MTAP and p16 immunohistochemical deficiency as surrogate marker for CDKN2A/B homozygous deletion in gliomas.

    Maragkou, Theoni / Reinhard, Stefan / Jungo, Patric / Pasquier, Baptiste / Neuenschwander, Maja / Schucht, Philippe / Vassella, Erik / Hewer, Ekkehard

    Pathology

    2023  Volume 55, Issue 4, Page(s) 466–477

    Abstract: Homozygous deletion (HD) of the CDKN2A/B locus has emerged as an unfavourable prognostic marker in diffuse gliomas, both IDH-mutant and IDH-wild-type. Testing for CDKN2A/B deletions can be performed by a variety of approaches, including copy number ... ...

    Abstract Homozygous deletion (HD) of the CDKN2A/B locus has emerged as an unfavourable prognostic marker in diffuse gliomas, both IDH-mutant and IDH-wild-type. Testing for CDKN2A/B deletions can be performed by a variety of approaches, including copy number variation (CNV) analysis based on gene array analysis, next generation sequencing (NGS) or fluorescence in situ hybridisation (FISH), but questions remain regarding the accuracy of testing modalities. In this study, we assessed: (1) the utility of S-methyl-5'-thioadenosine phosphorylase (MTAP) and cellular tumour suppressor protein pl61NK4a (p16) immunostainings as surrogate markers for CDKN2A/B HD in gliomas, and (2) the prognostic value of MTAP, across different histological tumour grades and IDH mutation status. One hundred consecutive cases of diffuse and circumscribed gliomas (Cohort 1) were collected, in order to correlate MTAP and p16 expression with the CDKN2A/B status in the CNV plot of each tumour. IDH1 R132H, ATRX and MTAP immunohistochemistry was performed on next generation tissue microarrays (ngTMAs) of 251 diffuse gliomas (Cohort 2) for implementing survival analysis. Complete loss of MTAP and p16 by immunohistochemistry was 100% and 90% sensitive as well as 97% and 89% specific for CDKN2A/B HD, respectively, as identified on CNV plot. Only two cases (2/100) with MTAP and p16 loss of expression did not demonstrate CDKN2A/B HD in CNV plot; however, FISH analysis confirmed the HD for CDKN2A/B. Moreover, MTAP deficiency was associated with shortened survival in IDH-mutant astrocytomas (n=75; median survival 61 vs 137 months; p<0.0001), IDH-mutant oligodendrogliomas (n=59; median survival 41 vs 147 months; p<0.0001) and IDH-wild-type gliomas (n=117; median survival 13 vs 16 months; p=0.011). In conclusion, MTAP immunostaining is an important complement for diagnostic work-up of gliomas, because of its excellent correlation with CDKN2A/B status, robustness, rapid turnaround time and low costs, and provides significant prognostic value in IDH-mutant astrocytomas and oligodendrogliomas, while p16 should be used cautiously.
    MeSH term(s) Humans ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Oligodendroglioma ; Homozygote ; DNA Copy Number Variations ; Sequence Deletion ; Gene Deletion ; Glioma/diagnosis ; Glioma/genetics ; Biomarkers ; Phosphorylases/genetics ; Astrocytoma/diagnosis ; Astrocytoma/genetics ; Brain Neoplasms/diagnosis ; Brain Neoplasms/genetics ; Isocitrate Dehydrogenase/genetics ; Mutation
    Chemical Substances Cyclin-Dependent Kinase Inhibitor p16 ; Biomarkers ; Phosphorylases (EC 2.4.1.-) ; Isocitrate Dehydrogenase (EC 1.1.1.41) ; CDKN2A protein, human
    Language English
    Publishing date 2023-03-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 7085-3
    ISSN 1465-3931 ; 0031-3025
    ISSN (online) 1465-3931
    ISSN 0031-3025
    DOI 10.1016/j.pathol.2023.01.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Comprehensive analysis of SARS-CoV-2 receptor proteins in human respiratory tissues identifies alveolar macrophages as potential virus entry site.

    Bräutigam, Konstantin / Reinhard, Stefan / Wartenberg, Martin / Forster, Stefan / Greif, Karen / Granai, Massimo / Bösmüller, Hans / Klingel, Karin / Schürch, Christian M

    Histopathology

    2023  Volume 82, Issue 6, Page(s) 846–859

    Abstract: Aims: COVID-19 has had enormous consequences on global health-care and has resulted in millions of fatalities. The exact mechanism and site of SARS-CoV-2 entry into the body remains insufficiently understood. Recently, novel virus receptors were ... ...

    Abstract Aims: COVID-19 has had enormous consequences on global health-care and has resulted in millions of fatalities. The exact mechanism and site of SARS-CoV-2 entry into the body remains insufficiently understood. Recently, novel virus receptors were identified, and alveolar macrophages were suggested as a potential viral entry cell type and vector for intra-alveolar virus transmission. Here, we investigated the protein expression of 10 well-known and novel virus entry molecules along potential entry sites in humans using immunohistochemistry.
    Methods and results: Samples of different anatomical sites from up to 93 patients were incorporated into tissue microarrays. Protein expression of ACE2, TMPRSS2, furin, CD147, C-type lectin receptors (CD169, CD209, CD299), neuropilin-1, ASGR1 and KREMEN1 were analysed. In lung tissues, at least one of the three receptors ACE2, ASGR1 or KREMEN1 was expressed in the majority of cases. Moreover, all the investigated molecules were found to be expressed in alveolar macrophages, and co-localisation with SARS-CoV-2 N-protein was demonstrated using dual immunohistochemistry in lung tissue from a COVID-19 autopsy. While CD169 and CD209 showed consistent protein expression in sinonasal, conjunctival and bronchiolar tissues, neuropilin-1 and ASGR1 were mostly absent, suggesting a minor relevance of these two molecules at these specific sites.
    Conclusion: Our results extend recent discoveries indicating a role for these molecules in virus entry at different anatomical sites. Moreover, they support the notion of alveolar macrophages being a potential entry cell for SARS-CoV-2.
    MeSH term(s) Humans ; SARS-CoV-2 ; COVID-19 ; Macrophages, Alveolar/metabolism ; Virus Internalization ; Angiotensin-Converting Enzyme 2/metabolism ; Neuropilin-1/metabolism ; Asialoglycoprotein Receptor/metabolism
    Chemical Substances Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Neuropilin-1 (144713-63-3) ; ASGR1 protein, human ; Asialoglycoprotein Receptor
    Language English
    Publishing date 2023-02-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 131914-0
    ISSN 1365-2559 ; 0309-0167
    ISSN (online) 1365-2559
    ISSN 0309-0167
    DOI 10.1111/his.14871
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Author Correction: An interpretable machine learning system for colorectal cancer diagnosis from pathology slides.

    Neto, Pedro C / Montezuma, Diana / Oliveira, Sara P / Oliveira, Domingos / Fraga, João / Monteiro, Ana / Monteiro, João / Ribeiro, Liliana / Gonçalves, Sofia / Reinhard, Stefan / Zlobec, Inti / Pinto, Isabel M / Cardoso, Jaime S

    NPJ precision oncology

    2024  Volume 8, Issue 1, Page(s) 83

    Language English
    Publishing date 2024-04-03
    Publishing country England
    Document type Published Erratum
    ISSN 2397-768X
    ISSN 2397-768X
    DOI 10.1038/s41698-024-00581-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: An interpretable machine learning system for colorectal cancer diagnosis from pathology slides.

    Neto, Pedro C / Montezuma, Diana / Oliveira, Sara P / Oliveira, Domingos / Fraga, João / Monteiro, Ana / Monteiro, João / Ribeiro, Liliana / Gonçalves, Sofia / Reinhard, Stefan / Zlobec, Inti / Pinto, Isabel M / Cardoso, Jaime S

    NPJ precision oncology

    2024  Volume 8, Issue 1, Page(s) 56

    Abstract: Considering the profound transformation affecting pathology practice, we aimed to develop a scalable artificial intelligence (AI) system to diagnose colorectal cancer from whole-slide images (WSI). For this, we propose a deep learning (DL) system that ... ...

    Abstract Considering the profound transformation affecting pathology practice, we aimed to develop a scalable artificial intelligence (AI) system to diagnose colorectal cancer from whole-slide images (WSI). For this, we propose a deep learning (DL) system that learns from weak labels, a sampling strategy that reduces the number of training samples by a factor of six without compromising performance, an approach to leverage a small subset of fully annotated samples, and a prototype with explainable predictions, active learning features and parallelisation. Noting some problems in the literature, this study is conducted with one of the largest WSI colorectal samples dataset with approximately 10,500 WSIs. Of these samples, 900 are testing samples. Furthermore, the robustness of the proposed method is assessed with two additional external datasets (TCGA and PAIP) and a dataset of samples collected directly from the proposed prototype. Our proposed method predicts, for the patch-based tiles, a class based on the severity of the dysplasia and uses that information to classify the whole slide. It is trained with an interpretable mixed-supervision scheme to leverage the domain knowledge introduced by pathologists through spatial annotations. The mixed-supervision scheme allowed for an intelligent sampling strategy effectively evaluated in several different scenarios without compromising the performance. On the internal dataset, the method shows an accuracy of 93.44% and a sensitivity between positive (low-grade and high-grade dysplasia) and non-neoplastic samples of 0.996. On the external test samples varied with TCGA being the most challenging dataset with an overall accuracy of 84.91% and a sensitivity of 0.996.
    Language English
    Publishing date 2024-03-05
    Publishing country England
    Document type Journal Article
    ISSN 2397-768X
    ISSN 2397-768X
    DOI 10.1038/s41698-024-00539-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Tumour budding/T cell infiltrates in colorectal cancer: proposal of a novel combined score.

    Dawson, Heather / Christe, Lucine / Eichmann, Micha / Reinhard, Stefan / Zlobec, Inti / Blank, Annika / Lugli, Alessandro

    Histopathology

    2020  Volume 76, Issue 4, Page(s) 572–580

    Abstract: Aims: The tumour-node-metastasis classification system is used for prognostication purposes and to guide patient management. However, in colorectal cancer (CRC), additional markers are needed to stratify prognostic subgroups. Two promising markers have ... ...

    Abstract Aims: The tumour-node-metastasis classification system is used for prognostication purposes and to guide patient management. However, in colorectal cancer (CRC), additional markers are needed to stratify prognostic subgroups. Two promising markers have emerged from large bodies of research: tumour budding and T cell host response (CD3, CD8 and CD45RO infiltrates). However, attempts to combine these two parameters have been sparse. The aim of this study was to perform an assessment of potential protagonists that could be used in a combined score (budding/T cell score, BTS).
    Methods and results: This descriptive, retrospective study was performed on a multipunch tissue microarray containing material from 345 patients with stages I-IV CRC. Areas from tumour centre, front and microenvironment were stained for pancytokeratin/CD3, pancytokeratin/CD8 and pancytokeratin/CD45RO. Tumour buds were scored manually and T cell infiltrates digitally using open-source software. Tumour buds, T cell counts and combined BTS were associated with clinicopathological features and overall survival (OS). A higher combined BTS score (buds/CD8, tumour centre) performed better than budding or CD8/CD3 alone in predicting nodal metastases (P < 0.0001, OR = 1.466, 95% CI = 1.115-1.928). Only higher BTS (buds/CD3) were significantly associated with poorer OS on multivariate analysis (P = 0.012, hazard ratio = 1.218, 95% confidence interval = 1.044-1.419).
    Conclusions: Although CD8
    MeSH term(s) Aged ; Colorectal Neoplasms/immunology ; Colorectal Neoplasms/pathology ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/pathology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; T-Lymphocytes/immunology ; T-Lymphocytes/pathology
    Language English
    Publishing date 2020-02-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 131914-0
    ISSN 1365-2559 ; 0309-0167
    ISSN (online) 1365-2559
    ISSN 0309-0167
    DOI 10.1111/his.14006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Mulitmodaler Neglekt und homonyme Gesichtsfeldausfälle : Teil II: Differentialdiagnostik und Therapie

    Reinhard, Stefan / Kerkhoff, Georg

    Praxis Ergotherapie

    2012  Volume 25, Issue 5, Page(s) 272–278

    Abstract: Der multimodale Neglekt und homonyme Gesichtsfeldausfälle haben ein ähnliches Erscheinungsbild, unterscheiden sich jedoch in ihrer Pathophysiologie und den gestörten Gehirnfunktionen. Eine genaue Differentialdiagnostik ist deshalb unumgänglich. Es werden ...

    Abstract Der multimodale Neglekt und homonyme Gesichtsfeldausfälle haben ein ähnliches Erscheinungsbild, unterscheiden sich jedoch in ihrer Pathophysiologie und den gestörten Gehirnfunktionen. Eine genaue Differentialdiagnostik ist deshalb unumgänglich. Es werden wirksame Therapieverfahren für beide Störungen beschrieben.
    Keywords Multimodaler Neglekt ; Gesichtsfeldausfall ; Diagnostik ; Therapie
    Language German
    Document type Article
    ZDB-ID 384295-2
    ISSN 0932-9692
    ISSN 0932-9692
    Database bibnet.org

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