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Article ; Online: Differential Role of the RAC1-Binding Proteins FAM49b (CYRI-B) and CYFIP1 in Platelets.

Sisario, Dmitri / Spindler, Markus / Ermer, Katharina J / Grütz, Noah / Nicolai, Leo / Gaertner, Florian / Machesky, Laura M / Bender, Markus

Cells

2024 Volume 13, Issue 4

Abstract: Platelet function at vascular injury sites is tightly regulated through the actin cytoskeleton. The Wiskott-Aldrich syndrome protein-family verprolin-homologous protein (WAVE)-regulatory complex (WRC) activates lamellipodia formation via ARP2/3, ... ...

Abstract	Platelet function at vascular injury sites is tightly regulated through the actin cytoskeleton. The Wiskott-Aldrich syndrome protein-family verprolin-homologous protein (WAVE)-regulatory complex (WRC) activates lamellipodia formation via ARP2/3, initiated by GTP-bound RAC1 interacting with the WRC subunit CYFIP1. The protein FAM49b (Family of Unknown Function 49b), also known as CYRI-B (CYFIP-Related RAC Interactor B), has been found to interact with activated RAC1, leading to the negative regulation of the WRC in mammalian cells. To investigate the role of FAM49b in platelet function, we studied platelet-specific
MeSH term(s)	Animals ; Mice ; Actin Cytoskeleton/metabolism ; Adaptor Proteins, Signal Transducing/metabolism ; Blood Platelets/metabolism ; Carrier Proteins/metabolism ; Fibrinogen/metabolism ; Mammals/metabolism ; rac1 GTP-Binding Protein/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; Carrier Proteins ; Cyfip1 protein, mouse ; Fibrinogen (9001-32-5) ; rac1 GTP-Binding Protein (EC 3.6.5.2) ; CYRIB protein, mouse ; Rac1 protein, mouse
Language	English
Publishing date	2024-02-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13040299
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Article ; Online: The WASH-complex subunit Strumpellin regulates integrin αIIbβ3 trafficking in murine platelets.

Schurr, Yvonne / Reil, Lucy / Spindler, Markus / Nieswandt, Bernhard / Machesky, Laura M / Bender, Markus

Scientific reports

2023 Volume 13, Issue 1, Page(s) 9526

Abstract: The platelet specific integrin αIIbβ3 mediates platelet adhesion, aggregation and plays a central role in thrombosis and hemostasis. In resting platelets, αIIbβ3 is expressed on the membrane surface and in intracellular compartments. Upon activation, the ...

Abstract	The platelet specific integrin αIIbβ3 mediates platelet adhesion, aggregation and plays a central role in thrombosis and hemostasis. In resting platelets, αIIbβ3 is expressed on the membrane surface and in intracellular compartments. Upon activation, the number of surface-expressed αIIbβ3 is increased by the translocation of internal granule pools to the plasma membrane. The WASH complex is the major endosomal actin polymerization-promoting complex and has been implicated in the generation of actin networks involved in endocytic trafficking of integrins in other cell types. The role of the WASH complex and its subunit Strumpellin in platelet function is still unknown. Here, we report that Strumpellin-deficient murine platelets display an approximately 20% reduction in integrin αIIbβ3 surface expression. While exposure of the internal αIIbβ3 pool after platelet activation was unaffected, the uptake of the αIIbβ3 ligand fibrinogen was delayed. The number of platelet α-granules was slightly but significantly increased in Strumpellin-deficient platelets. Quantitative proteome analysis of isolated αIIbβ3-positive vesicular structures revealed an enrichment of protein markers, which are associated with the endoplasmic reticulum, Golgi complex and early endosomes in Strumpellin-deficient platelets. These results point to a so far unidentified role of the WASH complex subunit Strumpellin in integrin αIIbβ3 trafficking in murine platelets.
MeSH term(s)	Animals ; Mice ; Blood Platelets/metabolism ; Integrin alpha2/metabolism ; Integrin beta3/metabolism ; Intracellular Signaling Peptides and Proteins/metabolism ; Megakaryocytes/metabolism ; Mice, Knockout
Chemical Substances	Integrin alpha2 ; Integrin beta3 ; Washc5 protein, mouse ; Intracellular Signaling Peptides and Proteins
Language	English
Publishing date	2023-06-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-36387-8
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Article ; Online: A Scoping Review on Work Experiences of Nurses After Being Diagnosed With Cancer.

You, Kai-Lin / Cummings, Meredith H / Bender, Catherine M / Fennimore, Laura A / Rosenzweig, Margaret Q / Dierkes, Andrew M / Raina, Ketki D / Hagan Thomas, Teresa

Oncology nursing forum

2023 Volume 50, Issue 6, Page(s) 714–724

Abstract: Problem identification: To map key concepts underpinning work-related studies about nurses with cancer and identify knowledge gaps.: Literature review: A search was conducted in the PubMed®, CINAHL®, and PsycINFO® databases for articles about nurses ... ...

Abstract	Problem identification: To map key concepts underpinning work-related studies about nurses with cancer and identify knowledge gaps. Literature review: A search was conducted in the PubMed®, CINAHL®, and PsycINFO® databases for articles about nurses with cancer and work-related topics published through March 2023. Data evaluation: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews Checklist was used to report results, and the JBI critical appraisal tools were used to assess the quality of studies. Eleven articles were included. Synthesis: The following four critical concepts were identified: role adjustments at work, cancer impacts on work, organizational support, and translating insights gained from cancer experience into work. Research gaps identified by the scoping review were a lack of theoretical or conceptual frameworks, lack of syntheses of main ideas, and lack of clear data about participants' socioeconomic status across studies. Implications for research: Minimal research exists to map predictors, outcomes, or intervention targets to guide organizational strategies to support nurses' retention in the nursing workforce. A guiding framework, recruitment of diverse nurses, and focus on the four critical concepts identified in this scoping review are suggested for future research.
MeSH term(s)	Humans ; Neoplasms ; Nursing Staff
Language	English
Publishing date	2023-10-24
Publishing country	United States
Document type	Systematic Review ; Review ; Journal Article
ZDB-ID	604886-9
ISSN	1538-0688 ; 0190-535X ; 1538-0688
ISSN (online)	1538-0688 ; 0190-535X
ISSN	1538-0688
DOI	10.1188/23.ONF.714-724
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Zs.A 1818: 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)
Zs.MO 414: Show issues

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Article ; Online: Patient Care Technician Staffing and Outcomes Among US Patients Receiving In-Center Hemodialysis.

Plantinga, Laura C / Bender, Alexis A / Urbanski, Megan / Douglas-Ajayi, Clarica / Morgan, Jennifer Craft / Woo, Karen / Jaar, Bernard G

JAMA network open

2024 Volume 7, Issue 3, Page(s) e241722

Abstract: Importance: Dialysis patient care technicians (PCTs) play a critical role in US in-center hemodialysis (HD) care, but little is known about the association of PCT staffing with patient outcomes at US HD facilities.: Objective: To estimate the ... ...

Abstract	Importance: Dialysis patient care technicians (PCTs) play a critical role in US in-center hemodialysis (HD) care, but little is known about the association of PCT staffing with patient outcomes at US HD facilities. Objective: To estimate the associations of in-center HD patient outcomes with facility-level PCT staffing. Design, setting, and participants: This was a retrospective cohort study, with data analysis performed from March 2023 to January 2024. Data on US patients with end-stage kidney disease and their treatment facilities were obtained from the US Renal Data System. Participants included patients (aged 18-100 years) initiating in-center HD between January 1, 2016, and December 31, 2018, who continued receiving in-center HD for 90 days or more and had data on PCT staffing at their initial treating HD facility. Exposure: Facility-level patient-to-PCT ratios (number of HD patients divided by the number of PCTs reported by the treating facility in the prior year), categorized into quartiles (highest quartile denotes the highest PCT burden). Main outcomes and measures: Patient-level outcomes included 1-year patient mortality, hospitalization, and transplantation. Associations of outcomes with quartile of patient-to-PCT ratio were estimated using incidence rate ratios (IRRs) from mixed-effects Poisson regression, with adjustment for patient demographics and clinical and facility factors. Results: A total of 236 126 patients (mean [SD] age, 63.1 [14.4] years; 135 952 [57.6%] male; 65 945 [27.9%] Black; 37 777 [16.0%] Hispanic; 153 637 [65.1%] White; 16 544 [7.0%] other race; 146 107 [61.9%] with diabetes) were included. After full adjustment, the highest vs lowest quartile of facility-level patient-to-PCT ratio was associated with a 7% higher rate of patient mortality (IRR, 1.07; 95% CI, 1.02-1.12), a 5% higher rate of hospitalization (IRR, 1.05; 95% CI, 1.02-1.08), an 8% lower rate of waitlisting (IRR, 0.92; 95% CI, 0.85-0.98), and a 20% lower rate of transplant (IRR, 0.80; 95% CI, 0.71-0.91). The highest vs lowest quartile of patient-to-PCT ratio was also associated with an 8% higher rate of sepsis-related hospitalization (IRR, 1.08; 95% CI, 1.03-1.14) and a 15% higher rate of vascular access-related hospitalization (IRR, 1.15; 95% CI, 1.03-1.28). Conclusions and relevance: These findings suggest that initiation of treatment in facilities with the highest patient-to-PCT ratios may be associated with worse early mortality, hospitalization, and transplantation outcomes. These results support further investigation of the impact of US PCT staffing on patient safety and quality of US in-center HD care.
MeSH term(s)	Humans ; Male ; Middle Aged ; Female ; Retrospective Studies ; Renal Dialysis ; Kidney Failure, Chronic/epidemiology ; Hospitalization ; Workforce
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Journal Article
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2024.1722
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Article ; Online: Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Trial.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2024 , Page(s) JCO2301279

Abstract: ... chemotherapy were treated with once weekly cisplatin (40 mg/m: Conclusion: Excellent outcomes can be ...

Abstract	Purpose: Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy. Materials and methods: Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS. Results: The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to the vagina (86%). External beam with either the three-dimensional or intensity modulated radiation treatment technique was followed by a boost delivered with brachytherapy or external beam. Patients randomly assigned to receive chemotherapy were treated with once weekly cisplatin (40 mg/m Conclusion: Excellent outcomes can be achieved for women with localized recurrences of endometrial cancer when treated with radiation therapy. The addition of chemotherapy does not improve PFS for patients treated with definitive radiation therapy for recurrent endometrial cancer and increases acute toxicity. Patients with low-grade and vaginal recurrences who constituted the majority of those enrolled are best treated with radiation therapy alone.
Language	English
Publishing date	2024-04-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.23.01279
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Zs.A 1847: 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)
Zs.MO 650: Show issues

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Article ; Online: Optimizing Quality of Life With Cognitive Impairment: A Study of End-of-Life Care in Assisted Living.

Arneson, Laura / Bender, Alexis A / Robert, Maggi N / Perkins, Molly M

Journal of the American Medical Directors Association

2019 Volume 21, Issue 5, Page(s) 692–696

Abstract: Objectives: Assisted living (AL) is an expanding site of end-of-life (EOL) care in the United States. Understanding determinants of quality of life (QoL) for AL residents near EOL is vital to optimize care for this growing population, most of whom have ... ...

Abstract	Objectives: Assisted living (AL) is an expanding site of end-of-life (EOL) care in the United States. Understanding determinants of quality of life (QoL) for AL residents near EOL is vital to optimize care for this growing population, most of whom have some degree of cognitive impairment (CI). This analysis aimed to identify factors associated with QoL in a diverse sample of AL residents with CI approaching EOL. Design: Observational cross-section design. Setting and participants: Data are from a 5-year study funded by the National Institute on Aging examining EOL care of residents in 7 diverse AL communities in metropolitan Atlanta (n = 67). Methods: CI was assessed with the Montreal Cognitive Assessment (scores ≤ 26) and QoL was determined with the self-reported QoL in Alzheimer's disease survey adapted for use in AL. Psychological distress was assessed using the Patient Health Questionnaire-4 and fatigue was assessed using the 13-item Functional Assessment of Chronic Illness Therapy Fatigue Scale. Initial descriptive analyses were followed by backward stepwise regression analyses to select a best-fitting model of QoL. Results: The final model predicted 27% of the variance in QoL. CI was not significantly correlated with QoL and was not retained in the final model. Pain and functional limitation also did not meet inclusion criteria (P ≤ .10) and were sequentially removed, producing a final model of QoL in terms of psychological distress (β = -0.28, P = .032), fatigue (β = -0.26, P = .048), and race (β = 0.21, P = .063). Conclusions and implications: The lack of a significant correlation between degree of CI and self-reported QoL suggests that AL residents have the potential to experience high QoL, despite CI. Interventions to reduce psychological distress and manage fatigue could be implemented during EOL care to attempt to improve QoL for AL residents with CI. The correlation between race and QoL warrants investigation into possible racial disparities in AL and EOL care.
MeSH term(s)	Cognitive Dysfunction ; Hospice Care ; Humans ; Quality of Life ; Surveys and Questionnaires ; Terminal Care
Language	English
Publishing date	2019-11-26
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, N.I.H., Extramural
ZDB-ID	2171030-2
ISSN	1538-9375 ; 1525-8610
ISSN (online)	1538-9375
ISSN	1525-8610
DOI	10.1016/j.jamda.2019.10.012
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Zs.A 5971: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Exposure considerations in human safety assessment: Report from an EPAA Partners' Forum.

Cronin, Mark T D / Ball, Nicholas / Beken, Sonja / Bender, Hans / Bercaru, Ofelia / Caneva, Laura / Corvaro, Marco / Currie, Richard A / Dawson, Jeffrey L / Desert, Paul / Escher, Sylvia E / Franco, Antonio / Irizar, Amaia / Mehta, Jyotigna M / Rogiers, Vera / Tremblay, Raphaël T / Westmoreland, Carl / Maxwell, Gavin

Regulatory toxicology and pharmacology : RTP

2023 Volume 144, Page(s) 105483

Abstract: Understanding and estimating the exposure to a substance is one of the fundamental requirements for safe manufacture and use. Many approaches are taken to determine exposure to substances, mainly driven by potential use and regulatory need. There are ... ...

Abstract	Understanding and estimating the exposure to a substance is one of the fundamental requirements for safe manufacture and use. Many approaches are taken to determine exposure to substances, mainly driven by potential use and regulatory need. There are many opportunities to improve and optimise the use of exposure information for chemical safety. The European Partnership for Alternative Approaches to Animal Testing (EPAA) therefore convened a Partners' Forum (PF) to explore exposure considerations in human safety assessment of industrial products to agree key conclusions for the regulatory acceptance of exposure assessment approaches and priority areas for further research investment. The PF recognised the widescale use of exposure information across industrial sectors with the possibilities of creating synergies between different sectors. Further, the PF acknowledged that the EPAA could make a significant contribution to promote the use of exposure data in human safety assessment, with an aim to address specific regulatory needs. To achieve this, research needs, as well as synergies and areas for potential collaboration across sectors, were identified.
MeSH term(s)	Animals ; Humans ; Animal Testing Alternatives ; Industry ; Commerce ; Risk Assessment
Language	English
Publishing date	2023-08-26
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	604672-1
ISSN	1096-0295 ; 0273-2300
ISSN (online)	1096-0295
ISSN	0273-2300
DOI	10.1016/j.yrtph.2023.105483
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Zs.A 1711: Show issues

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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: Repurposing HDAC inhibitors to enhance ribonuclease 4 and 7 expression and reduce urinary tract infection.

Schwartz, Laura / Bochter, M Skye / Simoni, Aaron / Bender, Kristin / de Dios Ruiz Rosado, Juan / Cotzomi-Ortega, Israel / Sanchez-Zamora, Yuriko I / Becknell, Brian / Linn, Sarah / Li, Birong / Santoro, Nicholas / Eichler, Tad / Spencer, John David

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 4, Page(s) e2213363120

Abstract: With the emergence of antibiotic-resistant bacteria, innovative approaches are needed for the treatment of urinary tract infections. Boosting antimicrobial peptide expression may provide an alternative to antibiotics. Here, we developed reporter cell ... ...

Abstract	With the emergence of antibiotic-resistant bacteria, innovative approaches are needed for the treatment of urinary tract infections. Boosting antimicrobial peptide expression may provide an alternative to antibiotics. Here, we developed reporter cell lines and performed a high-throughput screen of clinically used drugs to identify compounds that boost ribonuclease 4 and 7 expression (RNase 4 and 7), peptides that have antimicrobial activity against antibiotic-resistant uropathogens. This screen identified histone deacetylase (HDAC) inhibitors as effective RNase 4 and RNase 7 inducers. Validation studies in primary human kidney and bladder cells confirmed pan-HDAC inhibitors as well as the HDAC class I inhibitor, MS-275, induce RNase 4 and RNase 7 to protect human kidney and bladder cells from uropathogenic
MeSH term(s)	Humans ; Mice ; Animals ; Histone Deacetylase Inhibitors/pharmacology ; Escherichia coli/metabolism ; Drug Repositioning ; Ribonucleases/metabolism ; Urinary Tract Infections/drug therapy ; Urinary Tract Infections/microbiology ; Anti-Bacterial Agents
Chemical Substances	ribonuclease 4 (EC 3.1.-) ; Ribonuclease 7 (EC 3.1.27.-) ; entinostat (1ZNY4FKK9H) ; Histone Deacetylase Inhibitors ; Ribonucleases (EC 3.1.-) ; Anti-Bacterial Agents
Language	English
Publishing date	2023-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2213363120
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Zs.A 1148: Show issues

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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: Ex vivo anticoagulants affect human blood platelet biomechanics with implications for high-throughput functional mechanophenotyping.

Sachs, Laura / Wesche, Jan / Lenkeit, Lea / Greinacher, Andreas / Bender, Markus / Otto, Oliver / Palankar, Raghavendra

Communications biology

2022 Volume 5, Issue 1, Page(s) 86

Abstract: Inherited platelet disorders affecting the human platelet cytoskeleton result in increased bleeding risk. However, deciphering their impact on cytoskeleton-dependent intrinsic biomechanics of platelets remains challenging and represents an unmet need ... ...

Abstract	Inherited platelet disorders affecting the human platelet cytoskeleton result in increased bleeding risk. However, deciphering their impact on cytoskeleton-dependent intrinsic biomechanics of platelets remains challenging and represents an unmet need from a diagnostic and prognostic perspective. It is currently unclear whether ex vivo anticoagulants used during collection of peripheral blood impact the mechanophenotype of cellular components of blood. Using unbiased, high-throughput functional mechanophenotyping of single human platelets by real-time deformability cytometry, we found that ex vivo anticoagulants are a critical pre-analytical variable that differentially influences platelet deformation, their size, and functional response to agonists by altering the cytoskeleton. We applied our findings to characterize the functional mechanophenotype of platelets from a patient with Myosin Heavy Chain 9 (MYH9) related macrothrombocytopenia. Our data suggest that platelets from MYH9 p.E1841K mutation in humans affecting platelet non-muscle myosin heavy chain IIa (NMMHC-IIA) are biomechanically less deformable in comparison to platelets from healthy individuals.
MeSH term(s)	Adult ; Anticoagulants/pharmacology ; Biomechanical Phenomena ; Blood Platelets/classification ; Blood Platelets/drug effects ; Gene Expression Regulation/drug effects ; High-Throughput Screening Assays ; Humans ; Mutation ; Myosin Heavy Chains/genetics ; Platelet-Rich Plasma ; Specimen Handling
Chemical Substances	Anticoagulants ; MYH9 protein, human ; Myosin Heavy Chains (EC 3.6.4.1)
Language	English
Publishing date	2022-01-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-021-02982-6
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Article ; Online: Author Correction: Ex vivo anticoagulants affect human blood platelet biomechanics with implications for high-throughput functional mechanophenotyping.

Sachs, Laura / Wesche, Jan / Lenkeit, Lea / Greinacher, Andreas / Bender, Markus / Otto, Oliver / Palankar, Raghavendra

Communications biology

2022 Volume 5, Issue 1, Page(s) 187

Language	English
Publishing date	2022-02-23
Publishing country	England
Document type	Published Erratum
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-022-03130-4
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