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Article ; Online: The dementia care study (D-CARE): Recruitment strategies and demographic characteristics of participants in a pragmatic randomized trial of dementia care.

Alzheimer's & dementia : the journal of the Alzheimer's Association

2024 Volume 20, Issue 4, Page(s) 2575–2588

Abstract: Introduction: Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare.: Methods: Community-dwelling dyads were recruited for a pragmatic clinical trial evaluating three ... ...

Abstract	Introduction: Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare. Methods: Community-dwelling dyads were recruited for a pragmatic clinical trial evaluating three approaches to dementia care. Four clinical trial sites used shared and site-specific recruitment strategies to enroll health system patients. Results: Electronic health record (EHR) queries of patients with a diagnosis of dementia and engagement of their clinicians were the main recruitment strategies. A total of 2176 dyads were enrolled, with 80% recruited after the onset of the pandemic. PLWD had a mean age of 80.6 years (SD 8.5), 58.4% were women, and 8.8% were Hispanic/Latino, and 11.9% were Black/African American. Caregivers were mostly children of the PLWD (46.5%) or spouses/partners (45.2%), 75.8% were women, 9.4% were Hispanic/Latino, and 11.6% were Black/African American. Discussion: Health systems can successfully enroll diverse dyads in a pragmatic clinical trial.
MeSH term(s)	Child ; Humans ; Female ; Aged, 80 and over ; Male ; Dementia/epidemiology ; Dementia/therapy ; Caregivers ; Independent Living
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13698
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Article ; Online: Autocrine vitamin D signaling switches off pro-inflammatory programs of T

Chauss, Daniel / Freiwald, Tilo / McGregor, Reuben / Yan, Bingyu / Wang, Luopin / Nova-Lamperti, Estefania / Kumar, Dhaneshwar / Zhang, Zonghao / Teague, Heather / West, Erin E / Vannella, Kevin M / Ramos-Benitez, Marcos J / Bibby, Jack / Kelly, Audrey / Malik, Amna / Freeman, Alexandra F / Schwartz, Daniella M / Portilla, Didier / Chertow, Daniel S /

John, Susan / Lavender, Paul / Kemper, Claudia / Lombardi, Giovanna / Mehta, Nehal N / Cooper, Nichola / Lionakis, Michail S / Laurence, Arian / Kazemian, Majid / Afzali, Behdad

Nature immunology

2021 Volume 23, Issue 1, Page(s) 62–74

Abstract: The molecular mechanisms governing orderly shutdown and retraction of ... ...

Abstract	The molecular mechanisms governing orderly shutdown and retraction of CD4
MeSH term(s)	25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism ; Basic-Leucine Zipper Transcription Factors/metabolism ; Bronchoalveolar Lavage Fluid/cytology ; COVID-19/immunology ; COVID-19/pathology ; Complement C3a/immunology ; Complement C3b/immunology ; Humans ; Interferon-gamma/immunology ; Interleukin-10/immunology ; JNK Mitogen-Activated Protein Kinases/metabolism ; Lymphocyte Activation/immunology ; Receptors, Calcitriol/metabolism ; Respiratory Distress Syndrome/immunology ; Respiratory Distress Syndrome/pathology ; Respiratory Distress Syndrome/virology ; SARS-CoV-2/immunology ; STAT3 Transcription Factor/metabolism ; Signal Transduction/immunology ; Th1 Cells/immunology ; Transcription, Genetic/genetics ; Vitamin D/metabolism
Chemical Substances	BACH2 protein, human ; Basic-Leucine Zipper Transcription Factors ; IFNG protein, human ; IL10 protein, human ; Receptors, Calcitriol ; STAT3 Transcription Factor ; STAT3 protein, human ; VDR protein, human ; Interleukin-10 (130068-27-8) ; Vitamin D (1406-16-2) ; Complement C3a (80295-42-7) ; Complement C3b (80295-43-8) ; Interferon-gamma (82115-62-6) ; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (EC 1.14.15.18) ; CYP27B1 protein, human (EC 1.14.15.18) ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2021-11-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-021-01080-3
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Article: Expression of Cathepsins B, D, and G in WHO Grade I Meningioma.

Rahman, Rosanna M A / van Schaijik, Bede / Brasch, Helen D / Marsh, Reginald W / Wickremesekera, Agadha C / Johnson, Reuben / Woon, Kelvin / Tan, Swee T / Itinteang, Tinte

Frontiers in surgery

2019 Volume 6, Page(s) 6

Abstract: Aim: ...

Abstract	Aim:
Language	English
Publishing date	2019-03-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2773823-1
ISSN	2296-875X
ISSN	2296-875X
DOI	10.3389/fsurg.2019.00006
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Article: An autocrine Vitamin D-driven Th1 shutdown program can be exploited for COVID-19.

McGregor, Reuben / Chauss, Daniel / Freiwald, Tilo / Yan, Bingyu / Wang, Luopin / Nova-Lamperti, Estefania / Zhang, Zonghao / Teague, Heather / West, Erin E / Bibby, Jack / Kelly, Audrey / Malik, Amna / Freeman, Alexandra F / Schwartz, Daniella / Portilla, Didier / John, Susan / Lavender, Paul / Lionakis, Michail S / Mehta, Nehal N /

Kemper, Claudia / Cooper, Nichola / Lombardi, Giovanna / Laurence, Arian / Kazemian, Majid / Afzali, Behdad

bioRxiv : the preprint server for biology

2020

Abstract: Pro-inflammatory immune responses are necessary for effective pathogen clearance, but cause severe tissue damage if not shut down in a timely ... ...

Abstract	Pro-inflammatory immune responses are necessary for effective pathogen clearance, but cause severe tissue damage if not shut down in a timely manner
Keywords	covid19
Language	English
Publishing date	2020-07-19
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.07.18.210161
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Article ; Online: Questions remain about Vitamin D.

Rohn, Reuben

The Journal of adolescent health : official publication of the Society for Adolescent Medicine

2013 Volume 53, Issue 4, Page(s) 547–548

MeSH term(s)	Humans ; Vitamin D/administration & dosage ; Vitamin D Deficiency/drug therapy
Chemical Substances	Vitamin D (1406-16-2)
Language	English
Publishing date	2013-10
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	1063374-1
ISSN	1879-1972 ; 1054-139X
ISSN (online)	1879-1972
ISSN	1054-139X
DOI	10.1016/j.jadohealth.2013.06.023
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Article ; Online: An autocrine Vitamin D-driven Th1 shutdown program can be exploited for COVID-19

McGregor, Reuben / Chauss, Daniel / Freiwald, Tilo / Yan, Bingyu / Wang, Luopin / Nova-Lamperti, Estefania / Zhang, Zonghao / Teague, Heather / West, Erin / Bibby, Jack / Kelly, Audrey / Malik, Amna / Freeman, Alexandra / Schwartz, Daniella / Portilla, Didier / John, Susan / Lavender, Paul / Lionakis, Michail S / Mehta, Nehal N /

Kemper, Claudia / Cooper, Nichola / Lombardi, Giovanna / Laurence, Arian / Kazemian, Majid / Afzali, Ben

bioRxiv

Abstract: ... CD4+ T helper (Th) 1 cell responses by inducing expression of the vitamin D (VitD) receptor (VDR) and ...

Abstract	Pro-inflammatory immune responses are necessary for effective pathogen clearance, but cause severe tissue damage if not shut down in a timely manner. Excessive complement and IFN-γ-associated responses are known drivers of immunopathogenesis and are among the most highly induced immune programs in hyper-inflammatory SARS-CoV2 lung infection. The molecular mechanisms that govern orderly shutdown and retraction of these responses remain poorly understood. Here, we show that complement triggers contraction of IFN-γ producing CD4+ T helper (Th) 1 cell responses by inducing expression of the vitamin D (VitD) receptor (VDR) and CYP27B1, the enzyme that activates VitD, permitting T cells to both activate and respond to VitD. VitD then initiates the transition from pro-inflammatory IFN-γ+ Th1 cells to suppressive IL-10+ Th1 cells. This process is primed by dynamic changes in the epigenetic landscape of CD4+ T cells, generating super-enhancers and recruiting c-JUN and BACH2, a key immunoregulatory transcription factor. Accordingly, cells in psoriatic skin treated with VitD increased BACH2 expression, and BACH2 haplo-insufficient CD4+ T cells were defective in IL-10 production. As proof-of-concept, we show that CD4+ T cells in the bronchoalveolar lavage fluid (BALF) of patients with COVID-19 are Th1-skewed and that VDR is among the top regulators of genes induced by SARS-CoV2. Importantly, genes normally down-regulated by VitD were de-repressed in CD4+ BALF T cells of COVID-19, indicating that the VitD-driven shutdown program is impaired in this setting. The active metabolite of VitD, alfacalcidol, and cortico-steroids were among the top predicted pharmaceuticals that could normalize SARS-CoV2 induced genes. These data indicate that adjunct therapy with VitD in the context of other immunomodulatory drugs may be a beneficial strategy to dampen hyper-inflammation in severe COVID-19.
Keywords	covid19
Language	English
Publishing date	2020-07-19
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2020.07.18.210161
Database	COVID19

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Article ; Online: D-CARE: The Dementia Care Study: Design of a Pragmatic Trial of the Effectiveness and Cost Effectiveness of Health System-Based Versus Community-Based Dementia Care Versus Usual Dementia Care.

Reuben, David B / Gill, Thomas M / Stevens, Alan / Williamson, Jeff / Volpi, Elena / Lichtenstein, Maya / Jennings, Lee A / Tan, Zaldy / Evertson, Leslie / Bass, David / Weitzman, Lisa / Carnie, Martie / Wilson, Nancy / Araujo, Katy / Charpentier, Peter / Meng, Can / Greene, Erich J / Dziura, James / Liu, Jodi /

Unger, Erin / Yang, Mia / Currie, Katherine / Lenoir, Kristin M / Green, Aval-NaʼRee S / Abraham, Sitara / Vernon, Ashley / Samper-Ternent, Rafael / Raji, Mukaila / Hirst, Roxana M / Galloway, Rebecca / Finney, Glen R / Ladd, Ilene / Rahm, Alanna Kulchak / Borek, Pamela / Peduzzi, Peter

Journal of the American Geriatrics Society

2020 Volume 68, Issue 11, Page(s) 2492–2499

Abstract: ... Medicare claims.: Results: The results will be reported in the spring of 2024.: Conclusion: D-CARE ...

Abstract	Background/objectives: Although several approaches have been developed to provide comprehensive care for persons living with dementia (PWD) and their family or friend caregivers, the relative effectiveness and cost effectiveness of community-based dementia care (CBDC) versus health system-based dementia care (CBDC) and the effectiveness of both approaches compared with usual care (UC) are unknown. Design: Pragmatic randomized three-arm superiority trial. The unit of randomization is the PWD/caregiver dyad. Setting: Four clinical trial sites (CTSs) based in academic and clinical health systems. Participants: A total of 2,150 English- or Spanish-speaking PWD who are not receiving hospice or residing in a nursing home and their caregivers. Interventions: Eighteen months of (1) HSDC provided by a nurse practitioner or physician's assistant dementia care specialist who works within the health system, or (2) CBDC provided by a social worker or nurse care consultant who works at a community-based organization, or (3) UC with as needed referral to the Alzheimer's Association Helpline. Measurements: Primary outcomes: PWD behavioral symptoms and caregiver distress as measured by the Neuropsychiatric Inventory Questionnaire (NPI-Q) Severity and Modified Caregiver Strain Index scales. Secondary outcomes: NPI-Q Distress, caregiver unmet needs and confidence, and caregiver depressive symptoms. Tertiary outcomes: PWD long-term nursing home placement rates, caregiver-reported PWD functional status, cognition, goal attainment, "time spent at home," Dementia Burden Scale-Caregiver, a composite measure of clinical benefit, Quality of Life of persons with dementia, Positive Aspects of Caregiving, and cost effectiveness using intervention costs and Medicare claims. Results: The results will be reported in the spring of 2024. Conclusion: D-CARE will address whether emphasis on clinical support and tighter integration with other medical services has greater benefit than emphasis on social support that is tied more closely to community resources. It will also assess the effectiveness of both interventions compared with UC and will evaluate the cost effectiveness of each intervention.
MeSH term(s)	Aged ; Alzheimer Disease/therapy ; Caregiver Burden/psychology ; Community Health Services/organization & administration ; Comprehensive Health Care/methods ; Cost-Benefit Analysis ; Female ; Humans ; Male ; Multicenter Studies as Topic ; Pragmatic Clinical Trials as Topic ; Quality Improvement ; Quality of Life
Keywords	covid19
Language	English
Publishing date	2020-10-06
Publishing country	United States
Document type	Clinical Trial Protocol ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80363-7
ISSN	1532-5415 ; 0002-8614
ISSN (online)	1532-5415
ISSN	0002-8614
DOI	10.1111/jgs.16862
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Article ; Online: Vitamin D protects acute lymphoblastic leukemia cells from dexamethasone.

Antony, Reuben / Sheng, Xia / Ehsanipour, Ehsan A / Ng, Emily / Pramanik, Rocky / Klemm, Lars / Ichihara, Brian / Mittelman, Steven D

Leukemia research

2012 Volume 36, Issue 5, Page(s) 591–593

Abstract: Vitamin D deficiency has been linked with increased cancer risk, and vitamin D has been shown to be ... cytotoxic to some cancer cells in vitro. In the present study we evaluated whether vitamin D would have ... calcitriol, the active form of vitamin D, had no effect on leukemia cell proliferation. Calcitriol actually ...

Abstract	Vitamin D deficiency has been linked with increased cancer risk, and vitamin D has been shown to be cytotoxic to some cancer cells in vitro. In the present study we evaluated whether vitamin D would have antiproliferative or cytotoxic effects on human pre-B acute lymphoblastic leukemia cells. Contrary to our hypotheses, calcitriol, the active form of vitamin D, had no effect on leukemia cell proliferation. Calcitriol actually had a modest effect to impair dexamethasone cytotoxicity and induction of apoptosis. Further studies are needed to evaluate the effects of vitamin D on leukemia cells in vivo.
MeSH term(s)	Apoptosis/drug effects ; Calcitriol/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Dexamethasone/pharmacology ; Humans ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology
Chemical Substances	Dexamethasone (7S5I7G3JQL) ; Calcitriol (FXC9231JVH)
Language	English
Publishing date	2012-02-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	752396-8
ISSN	1873-5835 ; 0145-2126
ISSN (online)	1873-5835
ISSN	0145-2126
DOI	10.1016/j.leukres.2012.01.011
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Article ; Online: Immunomodulation of T Helper Cells by Tumor Microenvironment in Oral Cancer Is Associated With CCR8 Expression and Rapid Membrane Vitamin D Signaling Pathway.

Fraga, Marco / Yáñez, Milly / Sherman, Macarena / Llerena, Faryd / Hernandez, Mauricio / Nourdin, Guillermo / Álvarez, Francisco / Urrizola, Joaquín / Rivera, César / Lamperti, Liliana / Nova, Lorena / Castro, Silvia / Zambrano, Omar / Cifuentes, Alejandro / Campos, León / Moya, Sergio / Pastor, Juan / Nuñez, Marcelo / Gatica, Jorge /

Figueroa, Jorge / Zúñiga, Felipe / Salomón, Carlos / Cerda, Gustavo / Puentes, Ricardo / Labarca, Gonzalo / Vidal, Mabel / McGregor, Reuben / Nova-Lamperti, Estefania

Frontiers in immunology

2021 Volume 12, Page(s) 643298

Abstract: The immune system plays a key role in the protective response against oral cancer; however, the tumor microenvironment (TME) impairs this anti-cancer response by modulating T helper (Th) responses and promoting an anti-inflammatory environment. ... ...

Abstract	The immune system plays a key role in the protective response against oral cancer; however, the tumor microenvironment (TME) impairs this anti-cancer response by modulating T helper (Th) responses and promoting an anti-inflammatory environment. Regulatory T cells (Tregs) and Th2 effector cells (Teff) are associated with poor prognosis in oral squamous cell carcinoma (OSCC). However, the main immunomodulatory mechanisms associated with the enrichment of these subsets in OSCC remain unknown. We characterized Th-like lineages in Tregs and Teff and evaluated immunomodulatory changes induced by the TME in OSCC. Our phenotypic data revealed a higher distribution of tumour-infiltrating CCR8
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Female ; Gene Expression Regulation, Neoplastic/immunology ; Humans ; Immunomodulation ; Male ; Middle Aged ; Mouth Neoplasms/immunology ; Mouth Neoplasms/pathology ; Neoplasm Proteins/immunology ; Receptors, CCR8/immunology ; Signal Transduction/immunology ; Squamous Cell Carcinoma of Head and Neck/immunology ; Squamous Cell Carcinoma of Head and Neck/pathology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/pathology ; Th2 Cells/immunology ; Th2 Cells/pathology ; Tumor Microenvironment/immunology ; Vitamin D/immunology
Chemical Substances	CCR8 protein, human ; Neoplasm Proteins ; Receptors, CCR8 ; Vitamin D (1406-16-2)
Language	English
Publishing date	2021-05-07
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.2021.643298
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Article ; Online: Circulating tumour cells are linked to plasma D-dimer levels in patients with metastatic breast cancer.

Mego, Michal / Zuo, Zhuang / Gao, Hui / Cohen, Evan N / Giordano, Antonio / Tin, Sanda / Anfossi, Simone / Jackson, Summer / Woodward, Wendy / Ueno, Naoto T / Valero, Vicente / Alvarez, Ricardo H / Hortobagyi, Gabriel N / Khoury, Joseph D / Cristofanilli, Massimo / Reuben, James M

Thrombosis and haemostasis

2014 Volume 113, Issue 3, Page(s) 593–598

Abstract: Cancer is a risk factor for venous thromboembolism (VTE). Elevated plasma D-dimer and fibrinogen ... the presence of circulating tumour cells (CTCs) is a risk factor for VTE. The relationship between CTCs and D ... dimer is unknown. The aim of this study was to determine whether CTCs correlate with plasma D-dimer ...

Abstract	Cancer is a risk factor for venous thromboembolism (VTE). Elevated plasma D-dimer and fibrinogen levels are also risk factors for VTE. Furthermore, in patients with metastatic breast cancer (MBC), the presence of circulating tumour cells (CTCs) is a risk factor for VTE. The relationship between CTCs and D-dimer is unknown. The aim of this study was to determine whether CTCs correlate with plasma D-dimer level, fibrinogen level, and risk of VTE in MBC. This prospective study included 47 MBC patients treated from July 2009 through December 2010 at the MD Anderson Cancer Center. CTCs in peripheral blood were detected and enumerated using the CellSearch system. D-dimer and fibrinogen were measured in plasma at the time of CTC detection. Thirty-three patients (70 %) had ≥ 1 CTC, and 22 patients (47 %) had ≥ 5 CTCs. Patients with ≥ 1 CTC or ≥ 5 CTCs had significantly higher mean plasma D-dimer levels (µg/mL) than patients with no CTCs and < 5 CTCs (2.48 and 3.31 vs 0.80 and 0.84, respectively; p=0.006 for cut-off ≥ 1 CTC and p=0.003 for cut-off ≥ 5 CTCs). In multivariate analysis, presence of CTCs and number of metastases were positively associated with plasma D-dimer level. CTCs were not associated with plasma fibrinogen level. At median follow-up of 13.5 months, three of 33 patients (9 %) with ≥ 1 CTC had VTE, vs no patients with undetectable CTCs. In conclusion, the presence of CTCs was associated with higher levels of plasma D-dimer in MBC patients. This study further confirms an association between CTCs and risk of VTE.
MeSH term(s)	Adult ; Aged ; Biomarkers/blood ; Breast Neoplasms/blood ; Breast Neoplasms/complications ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/blood ; Carcinoma, Ductal, Breast/complications ; Carcinoma, Ductal, Breast/secondary ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Fibrin Fibrinogen Degradation Products/analysis ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Multivariate Analysis ; Neoplastic Cells, Circulating/pathology ; Prospective Studies ; Risk Assessment ; Risk Factors ; Texas ; Up-Regulation ; Venous Thromboembolism/blood ; Venous Thromboembolism/etiology ; Venous Thromboembolism/pathology
Chemical Substances	Biomarkers ; Fibrin Fibrinogen Degradation Products ; fibrin fragment D
Language	English
Publishing date	2014-11-06
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	518294-3
ISSN	2567-689X ; 0340-6245
ISSN (online)	2567-689X
ISSN	0340-6245
DOI	10.1160/TH14-07-0597
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