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Book: Adult day care therapeutic activity manual

Norman, Jennifer L. / Horton, Edward R.

a continuous quality improvement approach

1996

Author's details	Jennifer L. Norman ; Edward R. Horton
Keywords	Day Care / organization & administration ; Health Services for the Aged ; Recreation ; Quality Assurance, Health Care
Language	English
Size	VII, 199 S. : graph. Darst.
Publisher	Aspen
Publishing place	Gaithersburg, Md
Publishing country	United States
Document type	Book
HBZ-ID	HT007348898
ISBN	0-8342-0805-9 ; 978-0-8342-0805-6
Database	Catalogue ZB MED Medicine, Health

In stock of ZB MED Cologne/Königswinter

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1996 A 5918	order for loan	Magazin

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Article ; Online: Extracellular Matrix Production by Mesenchymal Stromal Cells in Hydrogels Facilitates Cell Spreading and Is Inhibited by FGF-2.

Horton, Edward R / Vallmajo-Martin, Queralt / Martin, Ivan / Snedeker, Jess G / Ehrbar, Martin / Blache, Ulrich

Advanced healthcare materials

2020 Volume 9, Issue 7, Page(s) e1901669

Abstract: In native tissues, the interaction between cells and the surrounding extracellular matrix (ECM) is reciprocal, as cells not only receive signals from the ECM but also actively remodel it through secretion of cell-derived ECM. However, very little is ... ...

Abstract	In native tissues, the interaction between cells and the surrounding extracellular matrix (ECM) is reciprocal, as cells not only receive signals from the ECM but also actively remodel it through secretion of cell-derived ECM. However, very little is known about the reciprocal interaction between cells and their secreted ECM within synthetic biomaterials that mimic the ECM for use in engineering of tissues for regenerative medicine or as tissue models. Here, poly(ethylene glycol) (PEG) hydrogels with fully defined biomaterial properties are used to investigate the emerging role of cell-derived ECM on culture outcomes. It is shown that human mesenchymal stromal cells (MSCs) secrete ECM proteins into the pericellular space early after encapsulation and that, even in the absence of material-presented cell adhesion motifs, cell-derived fibronectin enables cell spreading. Then, it is investigated how different culture conditions influence MSC ECM expression in hydrogels. Most strikingly, it is found by RNA sequencing that the fibroblast growth factor 2 (FGF-2) changes ECM gene expression and, in particular, decreases the expression of structural ECM components including fibrillar collagens. In summary, this work shows that cell-derived ECM is a guiding cue in 3D hydrogels and that FGF-2 is a potentially important ECM regulator within bioengineered cell and tissue systems.
MeSH term(s)	Cell Adhesion ; Extracellular Matrix ; Fibroblast Growth Factor 2/pharmacology ; Humans ; Hydrogels/pharmacology ; Mesenchymal Stem Cells
Chemical Substances	Hydrogels ; Fibroblast Growth Factor 2 (103107-01-3)
Language	English
Publishing date	2020-03-03
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649576-4
ISSN	2192-2659 ; 2192-2640
ISSN (online)	2192-2659
ISSN	2192-2640
DOI	10.1002/adhm.201901669
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Article: Organ-Specific, Fibroblast-Derived Matrix as a Tool for Studying Breast Cancer Metastasis.

Jensen, Adina R D / Horton, Edward R / Blicher, Lene H / Pietras, Elin J / Steinhauer, Cornelia / Reuten, Raphael / Schoof, Erwin M / Erler, Janine T

Cancers

2021 Volume 13, Issue 13

Abstract: During the metastatic process, breast cancer cells must come into contact with the extra-cellular matrix (ECM) at every step. The ECM provides both structural support and biochemical cues, and cell-ECM interactions can lead to changes in drug response. ... ...

Abstract	During the metastatic process, breast cancer cells must come into contact with the extra-cellular matrix (ECM) at every step. The ECM provides both structural support and biochemical cues, and cell-ECM interactions can lead to changes in drug response. Here, we used fibroblast-derived ECM (FDM) to perform high throughput drug screening of 4T1 breast cancer cells on metastatic organ ECM (lung), and we see that drug response differs from treatment on plastic. The FDMs that we can produce from different organs are abundant in and contains a complex mixture of ECM proteins. We also show differences in ECM composition between the primary site and secondary organ sites. Furthermore, we show that global kinase signalling of 4T1 cells on the ECM is relatively unchanged between organs, while changes in signalling compared to plastic are significant. Our study highlights the importance of context when testing drug response in vitro, showing that consideration of the ECM is critically important.
Language	English
Publishing date	2021-07-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13133331
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Article ; Online: Safety of Intravenous Cangrelor Administration for Antiplatelet Bridging in Hospitalized Patients: A Retrospective Study.

Johnson, Bryce V / Horton, Edward R / Domenico, Christopher / Nathan, Ashwin S / Fanaroff, Alexander C / Acker, Michael A / Kolansky, Daniel M

The Journal of invasive cardiology

2021 Volume 33, Issue 12, Page(s) E998–E1003

Abstract: Objective: We aimed to characterize outcomes associated with cangrelor administration used in an antiplatelet bridging strategy in real-world clinical scenarios within a large academic medical system.: Background: Cangrelor has been used for ... ...

Abstract	Objective: We aimed to characterize outcomes associated with cangrelor administration used in an antiplatelet bridging strategy in real-world clinical scenarios within a large academic medical system. Background: Cangrelor has been used for antiplatelet bridging in perioperative settings or for patients unable to take oral medications. Prior studies in these settings have reported bleeding rates from 0%-40%. Methods: Patients were retrospectively identified via chart review and included if they were over 18 years old, had coronary or peripheral arterial stents, and had received at least 1 hour of cangrelor infusion during inpatient admission. The primary endpoint was Bleeding Academic Research Consortium (BARC) 3-5 bleeding during cangrelor infusion or within 48 hours of discontinuation; secondary endpoints were bleeding events defined by Thrombolysis in Myocardial Infarction (TIMI), Global Use of Strategies to Open Occluded Arteries (GUSTO), and International Society on Thrombosis and Hemostasis (ISTH) criteria, as well as BARC 2 bleeding. Results: Thirty-one patients met the inclusion criteria. Cangrelor indications were bridging to procedure in 22 patients (71.0%) and inability to take oral P2Y12 inhibitors in 9 patients (29.0%). Twenty-three patients (74.2%) were men, 11 patients (35.5%) were in cardiogenic shock, and 4 patients (12.9%) were on extracorporeal membrane oxygenation (ECMO) at the time of administration. No patients received cangrelor for routine percutaneous coronary intervention. Of the 31 patients, 13 (41.9%) had BARC 3-5 bleeding and 7 (22.6%) expired during hospitalization. All 4 patients on ECMO suffered BARC 3-5 bleeding. Conclusions: We reviewed the use of cangrelor for antiplatelet bridging in real-world clinical scenarios and observed higher rates of clinically significant bleeding than seen in other similar studies. Our study suggests careful consideration when using cangrelor in a sick patient population.
MeSH term(s)	Adenosine Monophosphate/administration & dosage ; Adenosine Monophosphate/adverse effects ; Adenosine Monophosphate/analogs & derivatives ; Adolescent ; Blood Platelets/drug effects ; Humans ; Infusions, Intravenous ; Platelet Aggregation Inhibitors/administration & dosage ; Platelet Aggregation Inhibitors/adverse effects ; Retrospective Studies
Chemical Substances	Platelet Aggregation Inhibitors ; Adenosine Monophosphate (415SHH325A) ; cangrelor (6AQ1Y404U7)
Language	English
Publishing date	2021-11-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	1154372-3
ISSN	1557-2501 ; 1042-3931
ISSN (online)	1557-2501
ISSN	1042-3931
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Article ; Online: Fibroblast-derived matrix models desmoplastic properties and forms a prognostic signature in cancer progression.

Rafaeva, Maria / Jensen, Adina R D / Horton, Edward R / Zornhagen, Kamilla W / Strøbech, Jan E / Fleischhauer, Lutz / Mayorca-Guiliani, Alejandro E / Nielsen, Sebastian R / Grønseth, Dina S / Kuś, Filip / Schoof, Erwin M / Arnes, Luis / Koch, Manuel / Clausen-Schaumann, Hauke / Izzi, Valerio / Reuten, Raphael / Erler, Janine T

Frontiers in immunology

2023 Volume 14, Page(s) 1154528

Abstract: The desmoplastic reaction observed in many cancers is a hallmark of disease progression and prognosis, particularly in breast and pancreatic cancer. Stromal-derived extracellular matrix (ECM) is significantly altered in desmoplasia, and as such plays a ... ...

Abstract	The desmoplastic reaction observed in many cancers is a hallmark of disease progression and prognosis, particularly in breast and pancreatic cancer. Stromal-derived extracellular matrix (ECM) is significantly altered in desmoplasia, and as such plays a critical role in driving cancer progression. Using fibroblast-derived matrices (FDMs), we show that cancer cells have increased growth on cancer associated FDMs, when compared to FDMs derived from non-malignant tissue (normal) fibroblasts. We assess the changes in ECM characteristics from normal to cancer-associated stroma at the primary tumor site. Compositional, structural, and mechanical analyses reveal significant differences, with an increase in abundance of core ECM proteins, coupled with an increase in stiffness and density in cancer-associated FDMs. From compositional changes of FDM, we derived a 36-ECM protein signature, which we show matches in large part with the changes in pancreatic ductal adenocarcinoma (PDAC) tumor and metastases progression. Additionally, this signature also matches at the transcriptomic level in multiple cancer types in patients, prognostic of their survival. Together, our results show relevance of FDMs for cancer modelling and identification of desmoplastic ECM components for further mechanistic studies.
MeSH term(s)	Humans ; Prognosis ; Pancreatic Neoplasms/pathology ; Fibroblasts/metabolism ; Carcinoma, Pancreatic Ductal/pathology ; Extracellular Matrix Proteins ; Pancreatic Neoplasms
Chemical Substances	Extracellular Matrix Proteins
Language	English
Publishing date	2023-07-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1154528
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Article ; Online: Mechanosensitivity of integrin adhesion complexes: role of the consensus adhesome.

Horton, Edward R / Astudillo, Pablo / Humphries, Martin J / Humphries, Jonathan D

Experimental cell research

2016 Volume 343, Issue 1, Page(s) 7–13

Abstract: Cell and tissue stiffness have been known to contribute to both developmental and pathological signalling for some time, but the underlying mechanisms remain elusive. Integrins and their associated adhesion signalling complexes (IACs), which form a nexus ...

Abstract	Cell and tissue stiffness have been known to contribute to both developmental and pathological signalling for some time, but the underlying mechanisms remain elusive. Integrins and their associated adhesion signalling complexes (IACs), which form a nexus between the cell cytoskeleton and the extracellular matrix, act as a key force sensing and transducing unit in cells. Accordingly, there has been much interest in obtaining a systems-level understanding of IAC composition. Proteomic approaches have revealed the complexity of IACs and identified a large number of components that are regulated by cytoskeletal force. Here we review the function of the consensus adhesome, an assembly of core IAC proteins that emerged from a meta-analysis of multiple proteomic datasets, in the context of mechanosensing. As IAC components have been linked to a variety of diseases involved with rigidity sensing, the field is now in a position to define the mechanosensing function of individual IAC proteins and elucidate their mechanisms of action.
MeSH term(s)	Coordination Complexes ; Focal Adhesions/metabolism ; Humans ; Integrins/metabolism ; Models, Biological ; Proteomics ; Stress, Mechanical
Chemical Substances	Coordination Complexes ; Integrins
Language	English
Publishing date	2016-04-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1493-x
ISSN	1090-2422 ; 0014-4827
ISSN (online)	1090-2422
ISSN	0014-4827
DOI	10.1016/j.yexcr.2015.10.025
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Article ; Online: Proteomic Characterization of Caenorhabditis elegans Larval Development.

Xia, Tian / Horton, Edward R / Salcini, Anna Elisabetta / Pocock, Roger / Cox, Thomas R / Erler, Janine T

Proteomics

2017 Volume 18, Issue 2

Abstract: The nematode Caenorhabditis elegans is widely used as a model organism to study cell and developmental biology. Quantitative proteomics of C. elegans is still in its infancy and, so far, most studies have been performed on adult worm samples. Here, we ... ...

Abstract	The nematode Caenorhabditis elegans is widely used as a model organism to study cell and developmental biology. Quantitative proteomics of C. elegans is still in its infancy and, so far, most studies have been performed on adult worm samples. Here, we used quantitative mass spectrometry to characterize protein level changes across the four larval developmental stages (L1-L4) of C. elegans. In total, we identified 4130 proteins, and quantified 1541 proteins that were present across all four stages in three biological replicates from independent experiments. Using hierarchical clustering and functional ontological analyses, we identified 21 clusters containing proteins with similar protein profiles across the four stages, and highlighted the most overrepresented biological functions in each of these protein clusters. In addition, we used the dataset to identify putative larval stage-specific proteins in each individual developmental stage, as well as in the early and late developmental stages. In summary, this dataset provides system-wide analysis of protein level changes across the four C. elegans larval developmental stages, which serves as a useful resource for the C. elegans research community. MS data were deposited in ProteomeXchange (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository with the primary accession identifier PXD006676.
MeSH term(s)	Animals ; Caenorhabditis elegans/chemistry ; Caenorhabditis elegans/growth & development ; Caenorhabditis elegans Proteins/analysis ; Larva/chemistry ; Proteomics ; Tandem Mass Spectrometry
Chemical Substances	Caenorhabditis elegans Proteins
Language	English
Publishing date	2017-12-27
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2032093-0
ISSN	1615-9861 ; 1615-9853
ISSN (online)	1615-9861
ISSN	1615-9853
DOI	10.1002/pmic.201700238
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Zs.A 1868: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Suppression of tumor-associated neutrophils by lorlatinib attenuates pancreatic cancer growth and improves treatment with immune checkpoint blockade.

Nielsen, Sebastian R / Strøbech, Jan E / Horton, Edward R / Jackstadt, Rene / Laitala, Anu / Bravo, Marina C / Maltese, Giorgia / Jensen, Adina R D / Reuten, Raphael / Rafaeva, Maria / Karim, Saadia A / Hwang, Chang-Il / Arnes, Luis / Tuveson, David A / Sansom, Owen J / Morton, Jennifer P / Erler, Janine T

Nature communications

2021 Volume 12, Issue 1, Page(s) 3414

Abstract: Pancreatic ductal adenocarcinoma (PDAC) patients have a 5-year survival rate of only 8% largely due to late diagnosis and insufficient therapeutic options. Neutrophils are among the most abundant immune cell type within the PDAC tumor microenvironment ( ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) patients have a 5-year survival rate of only 8% largely due to late diagnosis and insufficient therapeutic options. Neutrophils are among the most abundant immune cell type within the PDAC tumor microenvironment (TME), and are associated with a poor clinical prognosis. However, despite recent advances in understanding neutrophil biology in cancer, therapies targeting tumor-associated neutrophils are lacking. Here, we demonstrate, using pre-clinical mouse models of PDAC, that lorlatinib attenuates PDAC progression by suppressing neutrophil development and mobilization, and by modulating tumor-promoting neutrophil functions within the TME. When combined, lorlatinib also improves the response to anti-PD-1 blockade resulting in more activated CD8 + T cells in PDAC tumors. In summary, this study identifies an effect of lorlatinib in modulating tumor-associated neutrophils, and demonstrates the potential of lorlatinib to treat PDAC.
MeSH term(s)	Aminopyridines ; Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/immunology ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/pathology ; Cell Line, Tumor/transplantation ; Disease Models, Animal ; Drug Synergism ; Female ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Lactams ; Lactams, Macrocyclic/pharmacology ; Lactams, Macrocyclic/therapeutic use ; Lymphocyte Activation/drug effects ; Lymphocytes, Tumor-Infiltrating/drug effects ; Lymphocytes, Tumor-Infiltrating/immunology ; Male ; Mice ; Mice, Transgenic ; Neutrophils/drug effects ; Neutrophils/immunology ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/immunology ; Pancreatic Neoplasms/pathology ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Programmed Cell Death 1 Receptor/metabolism ; Pyrazoles ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology
Chemical Substances	Aminopyridines ; Immune Checkpoint Inhibitors ; Lactams ; Lactams, Macrocyclic ; Pdcd1 protein, mouse ; Programmed Cell Death 1 Receptor ; Pyrazoles ; lorlatinib (OSP71S83EU)
Language	English
Publishing date	2021-06-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-23731-7
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Article ; Online: ISDoT: in situ decellularization of tissues for high-resolution imaging and proteomic analysis of native extracellular matrix.

Mayorca-Guiliani, Alejandro E / Madsen, Chris D / Cox, Thomas R / Horton, Edward R / Venning, Freja A / Erler, Janine T

Nature medicine

2017 Volume 23, Issue 7, Page(s) 890–898

Abstract: The extracellular matrix (ECM) is a master regulator of cellular phenotype and behavior. It has a crucial role in both normal tissue homeostasis and disease pathology. Here we present a fast and efficient approach to enhance the study of ECM composition ... ...

Abstract	The extracellular matrix (ECM) is a master regulator of cellular phenotype and behavior. It has a crucial role in both normal tissue homeostasis and disease pathology. Here we present a fast and efficient approach to enhance the study of ECM composition and structure. Termed in situ decellularization of tissues (ISDoT), it allows whole organs to be decellularized, leaving native ECM architecture intact. These three-dimensional decellularized tissues can be studied using high-resolution fluorescence and second harmonic imaging, and can be used for quantitative proteomic interrogation of the ECM. Our method is superior to other methods tested in its ability to preserve the structural integrity of the ECM, facilitate high-resolution imaging and quantitatively detect ECM proteins. In particular, we performed high-resolution sub-micron imaging of matrix topography in normal tissue and over the course of primary tumor development and progression to metastasis in mice, providing the first detailed imaging of the metastatic niche. These data show that cancer-driven ECM remodeling is organ specific, and that it is accompanied by comprehensive changes in ECM composition and topological structure. We also describe differing patterns of basement-membrane organization surrounding different types of blood vessels in healthy and diseased tissues. The ISDoT procedure allows for the study of native ECM structure under normal and pathological conditions in unprecedented detail.
MeSH term(s)	Animals ; Basement Membrane/metabolism ; Basement Membrane/ultrastructure ; Breast Neoplasms/metabolism ; Breast Neoplasms/ultrastructure ; Extracellular Matrix/metabolism ; Extracellular Matrix/ultrastructure ; Female ; Humans ; Imaging, Three-Dimensional ; Lactation ; Lung Neoplasms/metabolism ; Lung Neoplasms/secondary ; Lung Neoplasms/ultrastructure ; Lymph Nodes/metabolism ; Lymph Nodes/ultrastructure ; Lymphatic Metastasis ; Mammary Glands, Human/metabolism ; Mammary Glands, Human/ultrastructure ; Mammary Neoplasms, Experimental/metabolism ; Mammary Neoplasms, Experimental/ultrastructure ; Melanoma, Experimental/metabolism ; Melanoma, Experimental/ultrastructure ; Mice ; Optical Imaging ; Peripheral Nerves/metabolism ; Peripheral Nerves/ultrastructure ; Proteomics ; Tongue Neoplasms/metabolism ; Tongue Neoplasms/ultrastructure ; Tumor Microenvironment
Language	English
Publishing date	2017-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/nm.4352
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Article ; Online: Ischemia reduces inter-alpha inhibitor proteins in the brain of the ovine fetus.

Spasova, Mariya S / Chen, Xiaodi / Sadowska, Grazyna B / Horton, Edward R / Lim, Yow-Pin / Stonestreet, Barbara S

Developmental neurobiology

2017 Volume 77, Issue 6, Page(s) 726–737

Abstract: Hypoxic-ischemic (HI) brain injury is a major cause of neurological abnormalities in the perinatal period. Inflammation contributes to the evolution of HI brain injury. Inter-alpha inhibitor proteins (IAIPs) are a family of proteins that are part of the ... ...

Abstract	Hypoxic-ischemic (HI) brain injury is a major cause of neurological abnormalities in the perinatal period. Inflammation contributes to the evolution of HI brain injury. Inter-alpha inhibitor proteins (IAIPs) are a family of proteins that are part of the innate immune system. We have reported that endogenous IAIPs exhibit developmental changes in ovine brain and that exogenous IAIP treatment reduces neuronal death in HI neonatal rats. However, the effects of HI on endogenous IAIPs in brain have not been previously examined. In this study, we examined the effects of ischemia-reperfusion on endogenous IAIPs levels in fetal sheep brain. Cerebral cortex, cerebellum, cervical spinal cord, choroid plexus, and CSF were snap frozen from sham control fetuses at 127 days gestation and after 30-min of carotid occlusion and 4-, 24-, and 48-h of reperfusion. IAIP levels were determined by Western immunoblot. IAIP expressions of the 250 kDa Inter-alpha inhibitor (IaI) and 125 kDa Pre-alpha inhibitor (PaI) in cerebral cortex and PaI in cerebellum were reduced (p < 0.05) 4-h after ischemia compared with controls and returned toward control levels 24- and 48-h after ischemia. CSF PaI and IaI were reduced 48 h after ischemia. We conclude that IAIPs in cerebral cortex and cerebellum are reduced by brain ischemia, and return toward control levels between 24 and 48 h after ischemia. However, changes in CSF IAIPs were delayed, exhibiting decreases 48 h after ischemia. We speculate that the decreases in endogenous IAIPs reflect increased utilization, potentially suggesting that they have endogenous neuroprotective properties. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 726-737, 2017.
Language	English
Publishing date	2017-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2256184-5
ISSN	1932-846X ; 1097-4695 ; 1932-8451 ; 0022-3034
ISSN (online)	1932-846X ; 1097-4695
ISSN	1932-8451 ; 0022-3034
DOI	10.1002/dneu.22451
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