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Article: Fascination with epithelia: architecture, proteins, and functions.

Dale, Beverly A

2003 Volume 82, Issue 11, Page(s) 866–869

MeSH term(s)	Cell Differentiation ; Epithelial Cells/chemistry ; Epithelial Cells/immunology ; Humans ; Immunity, Mucosal ; Signal Transduction ; beta-Defensins/physiology
Chemical Substances	beta-Defensins
Language	English
Publishing date	2003-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80207-4
ISSN	1544-0591 ; 0022-0345
ISSN (online)	1544-0591
ISSN	0022-0345
DOI	10.1177/154405910308201104
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Ul III Zs.75: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 262: Show issues

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Article ; Online: Mechanistic Basis for the Differential Effects of Rivaroxaban and Apixaban on Global Tests of Coagulation.

Kim, Paul Y / Yeh, Calvin H / Dale, Brian J / Leslie, Beverly A / Stafford, Alan R / Fredenburgh, James C / Hirsh, Jack / Weitz, Jeffrey I

TH open : companion journal to thrombosis and haemostasis

2018 Volume 2, Issue 2, Page(s) e190–e201

Abstract: Rivaroxaban and apixaban are both small molecules that reversibly inhibit factor Xa. Compared with rivaroxaban, apixaban has minimal effects on the prothrombin time and activated partial thromboplastin time. To investigate this phenomenon, we used a ... ...

Abstract	Rivaroxaban and apixaban are both small molecules that reversibly inhibit factor Xa. Compared with rivaroxaban, apixaban has minimal effects on the prothrombin time and activated partial thromboplastin time. To investigate this phenomenon, we used a factor Xa-directed substrate in a buffer system. Although rivaroxaban and apixaban inhibited factor Xa with similar K
Language	English
Publishing date	2018-05-29
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2901738-5
ISSN	2512-9465 ; 2567-3459
ISSN (online)	2512-9465
ISSN	2567-3459
DOI	10.1055/s-0038-1649507
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Zs.A 7138: Show issues

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Article: Periodontal epithelium: a newly recognized role in health and disease.

Dale, Beverly A

Periodontology 2000

2002 Volume 30, Page(s) 70–78

MeSH term(s)	Anti-Infective Agents/pharmacology ; Bacterial Physiological Phenomena ; Basement Membrane/physiology ; Basement Membrane/ultrastructure ; Cytoskeleton/physiology ; Cytoskeleton/ultrastructure ; Disease Susceptibility ; Epithelial Attachment/pathology ; Epithelial Attachment/physiopathology ; Epithelial Cells/physiology ; Epithelial Cells/ultrastructure ; Epithelium/anatomy & histology ; Epithelium/immunology ; Epithelium/physiology ; Humans ; Immunity, Cellular/immunology ; Intercellular Junctions/physiology ; Intercellular Junctions/ultrastructure ; Membrane Proteins/physiology ; Periodontal Diseases/immunology ; Periodontal Diseases/microbiology ; Periodontal Diseases/pathology ; Periodontium/anatomy & histology ; Periodontium/immunology ; Periodontium/physiology ; Polymorphism, Genetic/genetics ; beta-Defensins/genetics ; beta-Defensins/physiology
Chemical Substances	Anti-Infective Agents ; Membrane Proteins ; beta-Defensins
Language	English
Publishing date	2002-09-16
Publishing country	Denmark
Document type	Journal Article ; Review
ZDB-ID	1200504-6
ISSN	1600-0757 ; 0906-6713
ISSN (online)	1600-0757
ISSN	0906-6713
DOI	10.1034/j.1600-0757.2002.03007.x
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Zs.A 4046: Show issues

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Article ; Online: Low-Intensity Adjuvant Chemotherapy for Breast Cancer in Older Women: Results From the Prospective Multicenter HOPE Trial.

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

2022 Volume 41, Issue 2, Page(s) 316–326

Abstract: Purpose: Older women with high-risk early breast cancer (EBC) benefit from adjuvant chemotherapy, but their treatment is frequently complicated by toxic side effects, resulting in dose reductions and delays. This makes it challenging for oncologists to ... ...

Abstract	Purpose: Older women with high-risk early breast cancer (EBC) benefit from adjuvant chemotherapy, but their treatment is frequently complicated by toxic side effects, resulting in dose reductions and delays. This makes it challenging for oncologists to maintain a relative dose intensity (RDI) ≥ 85%, as recommended for optimal curative-intent treatment. Understanding which women are at risk of receiving suboptimal RDI may inform treatment discussions and guide early, targeted supportive care or geriatric comanagement interventions. Methods: This was a prespecified secondary analysis of the HOPE trial, which enrolled women age ≥ 65 years with EBC initiating neoadjuvant or adjuvant chemotherapy. RDI was calculated as the ratio of delivered to planned chemotherapy dose intensity. The primary outcome was low RDI, defined as RDI < 85%. Multivariable logistic regression with stepwise selection was used to evaluate the association between baseline variables (demographic, clinical, and geriatric assessment) and low RDI. Survival probability was estimated using the Kaplan-Meier method, and the log-rank test was used to compare overall survival. Results: Three hundred twenty-two patients (median age at diagnosis, 70 years; range, 65-86 years) were included. The median follow-up was 4 years. Sixty-six patients (21%) had a low RDI. Age ≥ 76 years (odds ratio [OR], 2.57; 95% CI, 1.12 to 5.91; Conclusion: One in five older patients with EBC treated with standard chemotherapy received low RDI and had inferior survival outcomes. Older patients at risk for low RDI should be identified and targeted upfront before initiating chemotherapy.
MeSH term(s)	Humans ; Female ; Aged ; Breast Neoplasms ; Prospective Studies ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Cyclophosphamide ; Chemotherapy, Adjuvant/methods ; Retrospective Studies
Chemical Substances	Cyclophosphamide (8N3DW7272P)
Language	English
Publishing date	2022-12-01
Publishing country	United States
Document type	Multicenter Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.22.01440
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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)
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Article: Activation of protective responses in oral epithelial cells by Fusobacterium nucleatum and human beta-defensin-2.

Yin, Lei / Dale, Beverly A

Journal of medical microbiology

2007 Volume 56, Issue Pt 7, Page(s) 976–987

Abstract: Oral epithelia are constantly exposed to non-pathogenic (commensal) bacteria, but generally remain healthy and uninflamed. Fusobacterium nucleatum, an oral commensal bacterium, strongly induces human beta-defensin-2 (hBD2), an antimicrobial and ... ...

Abstract	Oral epithelia are constantly exposed to non-pathogenic (commensal) bacteria, but generally remain healthy and uninflamed. Fusobacterium nucleatum, an oral commensal bacterium, strongly induces human beta-defensin-2 (hBD2), an antimicrobial and immunomodulatory peptide, in gingival epithelial cells (GECs). hBD2 is also expressed in normal oral tissue leading to the hypothesis that oral epithelia are in an activated state with respect to innate immune responses under normal in vivo conditions. In order to test this hypothesis, global gene expression was evaluated in GECs in response to stimulation by an F. nucleatum cell wall (FnCW) preparation and to hBD2 peptide. FnCW treatment altered 829 genes, while hBD2 altered 209 genes (P<0.005, ANOVA). Many induced genes were associated with the gene ontology categories of immune responses and defence responses. Consistent with the hypothesis, similar responses were activated by commensal bacteria and hBD2. These responses included up-regulation of common antimicrobial effectors and chemokines, and down-regulation of proliferation markers. In addition, FnCW up-regulated multiple protease inhibitors, and suppressed NF-kappaB function and the ubiquitin/proteasome system. These global changes may protect the tissue from inflammatory damage. Both FnCW and hBD2 also up-regulated genes that may enhance the epithelial barrier. The findings suggest that both commensal bacteria and hBD2 activate protective responses of GECs and play an important role in immune modulation in the oral cavity.
MeSH term(s)	Cells, Cultured ; Cytokines/genetics ; Cytokines/metabolism ; Epithelial Cells/immunology ; Epithelial Cells/microbiology ; Fusobacterium nucleatum/immunology ; Gene Expression Regulation/drug effects ; Gingiva/cytology ; Gingiva/immunology ; Gingiva/microbiology ; Humans ; Immunity, Innate ; Inflammation ; Oligonucleotide Array Sequence Analysis ; Protease Inhibitors/metabolism ; Proteins/genetics ; Proteins/metabolism ; beta-Defensins/metabolism ; beta-Defensins/pharmacology
Chemical Substances	Cytokines ; Protease Inhibitors ; Proteins ; beta-Defensins
Language	English
Publishing date	2007-06-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	218356-0
ISSN	1473-5644 ; 0022-2615
ISSN (online)	1473-5644
ISSN	0022-2615
DOI	10.1099/jmm.0.47198-0
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Zs.A 634: Show issues

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Article ; Online: Associations of Uncertainty With Psychological Health and Quality of Life in Older Adults With Advanced Cancer.

Verduzco-Aguirre, Haydee C / Babu, Dilip / Mohile, Supriya G / Bautista, Javier / Xu, Huiwen / Culakova, Eva / Canin, Beverly / Zhang, Yingzi / Wells, Megan / Epstein, Ronald M / Duberstein, Paul / McHugh, Colin / Dale, William / Conlin, Alison / Bearden, James / Berenberg, Jeffrey / Tejani, Mohamedtaki / Loh, Kah Poh

Journal of pain and symptom management

2020 Volume 61, Issue 2, Page(s) 369–376.e1

Abstract: Context: Older adults with advanced cancer face uncertainty related to their disease and treatment.: Objectives: To evaluate the associations of uncertainty with psychological health and quality of life (QoL) in older adults with advanced cancer.: ... ...

Abstract	Context: Older adults with advanced cancer face uncertainty related to their disease and treatment. Objectives: To evaluate the associations of uncertainty with psychological health and quality of life (QoL) in older adults with advanced cancer. Methods: Secondary cross-sectional analysis of baseline data from a national clustered geriatric assessment trial. Patients 70 years and older with advanced cancer considering a new line of chemotherapy were recruited. We measured uncertainty using the modified nine-item Mishel Uncertainty in Illness Scale. Dependent variables included anxiety (Generalized Anxiety Disorder-7), depression (Generalized Depression Scale-15), distress (distress thermometer), QoL (Functional Assessment of Cancer Therapy-General), and emotional well-being (Functional Assessment of Cancer Therapy-General subscale). We used multivariate linear regression analyses to evaluate the association of uncertainty with each dependent variable. We conducted a partial least squares analysis with a variable importance in projection (VIP) plot to assess the contribution of individual variables to the model. Variables with a VIP <0.8 were considered less influential. Results: We included 527 patients (median age 76 years; range 70-96). In multivariate analyses, higher levels of uncertainty were significantly associated with greater anxiety (β = 0.11; SE = 0.04), depression (β = 0.09; SE = 0.02), distress (β = 0.12; SE = 0.02), as well as lower QoL (β = -1.08; SE = 0.11) and emotional well-being (β = -0.29; SE = 0.03); the effect sizes were considered small. Uncertainty items related to disease and treatment were most strongly associated with psychological health and QoL scores (all VIP >0.8). Conclusion: Uncertainty among older patients with advanced cancer is associated with worse psychological health and QoL. Tailored uncertainty management strategies are warranted.
MeSH term(s)	Aged ; Aged, 80 and over ; Anxiety/epidemiology ; Cross-Sectional Studies ; Depression/epidemiology ; Humans ; Mental Health ; Neoplasms/therapy ; Quality of Life ; Uncertainty
Language	English
Publishing date	2020-08-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639142-4
ISSN	1873-6513 ; 0885-3924
ISSN (online)	1873-6513
ISSN	0885-3924
DOI	10.1016/j.jpainsymman.2020.08.012
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Article: Antimicrobial peptides in the oral environment: expression and function in health and disease.

Dale, Beverly A / Fredericks, L Page

Current issues in molecular biology

2005 Volume 7, Issue 2, Page(s) 119–133

Abstract: The oral cavity is a unique environment in which antimicrobial peptides play a key role in maintaining health and may have future therapeutic applications. Present evidence suggests that alpha-defensins, beta-defensins, LL-37, histatin, and other ... ...

Abstract	The oral cavity is a unique environment in which antimicrobial peptides play a key role in maintaining health and may have future therapeutic applications. Present evidence suggests that alpha-defensins, beta-defensins, LL-37, histatin, and other antimicrobial peptides and proteins have distinct but overlapping roles in maintaining oral health and preventing bacterial, fungal, and viral adherence and infection. The expression of the inducible hBD-2 in normal oral epithelium, in contrast to other epithelia, and the apparent differential signaling in response to commensal and pathogenic organisms, provides new insights into innate immunity in this body site. Commensal bacteria are excellent inducers of hBD-2 in oral epithelial cells, suggesting that the commensal bacterial community acts in a manner to benefit the overall innate immune readiness of oral epithelia. This may have major significance for understanding host defense in the complex oral environment.
MeSH term(s)	Animals ; Anti-Bacterial Agents/therapeutic use ; Antimicrobial Cationic Peptides/genetics ; Antimicrobial Cationic Peptides/metabolism ; Antimicrobial Cationic Peptides/physiology ; Epithelium/immunology ; Epithelium/metabolism ; Epithelium/microbiology ; Gingiva/immunology ; Gingiva/metabolism ; Immunity, Innate ; Mice ; Mouth Mucosa/immunology ; Mouth Mucosa/metabolism ; Mouth Mucosa/microbiology
Chemical Substances	Anti-Bacterial Agents ; Antimicrobial Cationic Peptides
Language	English
Publishing date	2005-07-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	2000024-8
ISSN	1467-3037
ISSN	1467-3037
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Book ; Online: Evaluating AI systems under uncertain ground truth

a case study in dermatology

2023

Abstract: For safety, AI systems in health undergo thorough evaluations before deployment, validating their predictions against a ground truth that is assumed certain. However, this is actually not the case and the ground truth may be uncertain. Unfortunately, ... ...

Abstract	For safety, AI systems in health undergo thorough evaluations before deployment, validating their predictions against a ground truth that is assumed certain. However, this is actually not the case and the ground truth may be uncertain. Unfortunately, this is largely ignored in standard evaluation of AI models but can have severe consequences such as overestimating the future performance. To avoid this, we measure the effects of ground truth uncertainty, which we assume decomposes into two main components: annotation uncertainty which stems from the lack of reliable annotations, and inherent uncertainty due to limited observational information. This ground truth uncertainty is ignored when estimating the ground truth by deterministically aggregating annotations, e.g., by majority voting or averaging. In contrast, we propose a framework where aggregation is done using a statistical model. Specifically, we frame aggregation of annotations as posterior inference of so-called plausibilities, representing distributions over classes in a classification setting, subject to a hyper-parameter encoding annotator reliability. Based on this model, we propose a metric for measuring annotation uncertainty and provide uncertainty-adjusted metrics for performance evaluation. We present a case study applying our framework to skin condition classification from images where annotations are provided in the form of differential diagnoses. The deterministic adjudication process called inverse rank normalization (IRN) from previous work ignores ground truth uncertainty in evaluation. Instead, we present two alternative statistical models: a probabilistic version of IRN and a Plackett-Luce-based model. We find that a large portion of the dataset exhibits significant ground truth uncertainty and standard IRN-based evaluation severely over-estimates performance without providing uncertainty estimates.
Keywords	Computer Science - Machine Learning ; Computer Science - Computer Vision and Pattern Recognition ; Statistics - Methodology ; Statistics - Machine Learning
Subject code	006
Publishing date	2023-07-05
Publishing country	us
Document type	Book ; Online
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Article ; Online: Shared Goal Setting in Team-Based Geriatric Oncology.

Magnuson, Allison / Wallace, James / Canin, Beverly / Chow, Selina / Dale, William / Mohile, Supriya G / Hamel, Lauren M

Journal of oncology practice

2016 Volume 12, Issue 11, Page(s) 1115–1122

Abstract: We present the case of a 92-year-old man, MH, who was given a diagnosis of colorectal cancer. His primary care physician, surgeon, geriatric oncologist, and family members all played important roles in his care. MH's case is an example of a lack of ... ...

Abstract	We present the case of a 92-year-old man, MH, who was given a diagnosis of colorectal cancer. His primary care physician, surgeon, geriatric oncologist, and family members all played important roles in his care. MH's case is an example of a lack of explicit shared goal setting by the health care providers with the patient and family members and how that impeded care planning and health. This case demonstrates the importance of explicitly discussing and establishing shared goals in team-based cancer care delivery early on and throughout the care process, especially for older adults. Each individual member's goals should be understood as they fit within the overarching shared team goals. We emphasize that shared goal setting and alignment of individual goals is a dynamic process that must occur several times at critical decision points throughout a patient's care continuum. Providers and researchers can use this illustrative case to consider their own work and contemplate how shared goal setting can improve patient-centered care and health outcomes in various team-based care settings. Shared goal setting among team members has been demonstrated to improve outcomes in other contexts. However, we stress, that little investigation into the impact of shared goal setting on team-based cancer care delivery has been conducted. We list immediate research goals within team-based cancer care delivery that can provide a foundation for the understanding of the process and outcomes of shared goal setting.
MeSH term(s)	Aged, 80 and over ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/radiotherapy ; Geriatric Assessment ; Geriatrics ; Goals ; Humans ; Male ; Medical Oncology ; Patient Care Team/organization & administration
Language	English
Publishing date	2016-09-30
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2236338-5
ISSN	1935-469X ; 1554-7477
ISSN (online)	1935-469X
ISSN	1554-7477
DOI	10.1200/JOP.2016.013623
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Article ; Online: Caries induced cytokine network in the odontoblast layer of human teeth.

Horst, Orapin V / Horst, Jeremy A / Samudrala, Ram / Dale, Beverly A

BMC immunology

2011 Volume 12, Page(s) 9

Abstract: Background: Immunologic responses of the tooth to caries begin with odontoblasts recognizing carious bacteria. Inflammatory propagation eventually leads to tooth pulp necrosis and danger to health. The present study aims to determine cytokine gene ... ...

Abstract	Background: Immunologic responses of the tooth to caries begin with odontoblasts recognizing carious bacteria. Inflammatory propagation eventually leads to tooth pulp necrosis and danger to health. The present study aims to determine cytokine gene expression profiles generated within human teeth in response to dental caries in vivo and to build a mechanistic model of these responses and the downstream signaling network. Results: We demonstrate profound differential up-regulation of inflammatory genes in the odontoblast layer (ODL) in human teeth with caries in vivo, while the pulp remains largely unchanged. Interleukins, chemokines, and all tested receptors thereof were differentially up-regulated in ODL of carious teeth, well over one hundred-fold for 35 of 84 genes. By interrogating reconstructed protein interaction networks corresponding to the differentially up-regulated genes, we develop the hypothesis that pro-inflammatory cytokines highly expressed in ODL of carious teeth, IL-1β, IL-1α, and TNF-α, carry the converged inflammatory signal. We show that IL1β amplifies antimicrobial peptide production in odontoblasts in vitro 100-fold more than lipopolysaccharide, in a manner matching subsequent in vivo measurements. Conclusions: Our data suggest that ODL amplifies bacterial signals dramatically by self-feedback cytokine-chemokine signal-receptor cycling, and signal convergence through IL1R1 and possibly others, to increase defensive capacity including antimicrobial peptide production to protect the tooth and contain the battle against carious bacteria within the dentin.
MeSH term(s)	Antimicrobial Cationic Peptides/biosynthesis ; Cytokines/genetics ; Cytokines/metabolism ; DNA, Complementary/genetics ; Dental Caries/genetics ; Dental Caries/immunology ; Dental Caries/pathology ; Dental Pulp/immunology ; Dental Pulp/pathology ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks/genetics ; Humans ; Immunity, Innate/genetics ; Inflammation Mediators/metabolism ; Models, Immunological ; Odontoblasts/immunology ; Odontoblasts/pathology ; Oligonucleotide Array Sequence Analysis ; Protective Agents/metabolism ; Receptors, Cytokine/genetics ; Receptors, Cytokine/metabolism ; Signal Transduction/genetics ; Tooth/immunology ; Tooth/pathology ; Transcription, Genetic
Chemical Substances	Antimicrobial Cationic Peptides ; Cytokines ; DNA, Complementary ; Inflammation Mediators ; Protective Agents ; Receptors, Cytokine
Language	English
Publishing date	2011-01-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2041500-X
ISSN	1471-2172 ; 1471-2172
ISSN (online)	1471-2172
ISSN	1471-2172
DOI	10.1186/1471-2172-12-9
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