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  1. Article ; Online: A flexible matching strategy for matched nested case-control studies.

    Ratanatharathorn, Andrew / Mooney, Stephen J / Rybicki, Benjamin A / Rundle, Andrew G

    Annals of epidemiology

    2023  Volume 86, Page(s) 49–56.e3

    Abstract: Purpose: Individual matching in case-control studies improves statistical efficiency over random selection of controls but can lead to selection bias if cases are excluded due to the lack of appropriate controls or residual confounding with less strict ... ...

    Abstract Purpose: Individual matching in case-control studies improves statistical efficiency over random selection of controls but can lead to selection bias if cases are excluded due to the lack of appropriate controls or residual confounding with less strict matching criteria. We introduce flex matching, an algorithm using multiple rounds of control selection with successively relaxed matching criteria to select controls for cases.
    Methods: We simulated exposure-disease relationships in multiple cohort data sets with a range of confounding scenarios and conducted 16,800,000 nested case-control studies, comparing random selection of controls, strict matching, and flex matching. We computed average bias and statistical efficiency in estimates of exposure-disease relationships under each matching strategy.
    Results: On average, flex matching produced the least biased estimates of exposure-disease associations with the smallest standard errors. Strict matching algorithms that excluded cases for whom matched controls could not be identified produced biased estimates with larger standard errors. Estimates from studies with random assignment of controls were relatively unbiased, but the standard errors were larger than from studies using flex matching.
    Conclusions: Flex matching should be considered for case-control designs, especially for biomarker studies where matching on technical artifacts is necessary and maximizing efficiency is a priority.
    Language English
    Publishing date 2023-07-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1074355-8
    ISSN 1873-2585 ; 1047-2797
    ISSN (online) 1873-2585
    ISSN 1047-2797
    DOI 10.1016/j.annepidem.2023.06.023
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  2. Article ; Online: Multiple Correspondence Analysis and HLA-Associations of Organ Involvement in a Large Cohort of African-American and European-American Patients with Sarcoidosis.

    Rasmussen, Astrid / Dawkins, Bryan A / Li, Chuang / Pezant, Nathan / Levin, Albert M / Rybicki, Benjamin A / Iannuzzi, Michael C / Montgomery, Courtney G

    Lung

    2023  Volume 201, Issue 3, Page(s) 297–302

    Abstract: Sarcoidosis is a systemic granulomatous disease with predominant pulmonary involvement and vast heterogeneity of clinical manifestations and disease outcomes. African American (AA) patients suffer greater morbidity and mortality. Using Multiple ... ...

    Abstract Sarcoidosis is a systemic granulomatous disease with predominant pulmonary involvement and vast heterogeneity of clinical manifestations and disease outcomes. African American (AA) patients suffer greater morbidity and mortality. Using Multiple Correspondence Analysis, we identified seven clusters of organ involvement in European American (EA; n = 385) patients which were similar to those previously described in a Pan-European (GenPhenReSa) and a Spanish cohort (SARCOGEAS). In contrast, AA (n = 987) had six, less well-defined and overlapping clusters with little similarity to the cluster identified in the EA cohort evaluated at the same U.S. institutions. Association of cluster membership with two-digit HLA-DRB1 alleles demonstrated ancestry-specific patterns of association and replicated known HLA effects.These results further support the notion that genetically influenced immune risk profiles, which differ based on ancestry, play a role in phenotypic heterogeneity. Dissecting such risk profiles will move us closer to personalized medicine for this complex disease.
    MeSH term(s) Humans ; Alleles ; Black or African American/genetics ; Genetic Predisposition to Disease ; HLA-DRB1 Chains/genetics ; Sarcoidosis/genetics ; White/genetics
    Chemical Substances HLA-DRB1 Chains
    Language English
    Publishing date 2023-06-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 6165-7
    ISSN 1432-1750 ; 0341-2040
    ISSN (online) 1432-1750
    ISSN 0341-2040
    DOI 10.1007/s00408-023-00626-6
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  3. Article: Corrigendum: Sex differences in the genetics of sarcoidosis across European and African ancestry populations.

    Xiong, Ying / Kullberg, Susanna / Garman, Lori / Pezant, Nathan / Ellinghaus, David / Vasila, Vasiliki / Eklund, Anders / Rybicki, Benjamin A / Iannuzzi, Michael C / Schreiber, Stefan / Müller-Quernheim, Joachim / Montgomery, Courtney G / Grunewald, Johan / Padyukov, Leonid / Rivera, Natalia V

    Frontiers in medicine

    2024  Volume 11, Page(s) 1382584

    Abstract: This corrects the article DOI: 10.3389/fmed.2023.1132799.]. ...

    Abstract [This corrects the article DOI: 10.3389/fmed.2023.1132799.].
    Language English
    Publishing date 2024-02-21
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2024.1382584
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  4. Article ; Online: Patterns of B-cell lymphocyte expression changes in pre- and post-malignant prostate tissue are associated with prostate cancer progression.

    Sadasivan, Sudha M / Loveless, Ian M / Chen, Yalei / Gupta, Nilesh S / Sanii, Ryan / Bobbitt, Kevin R / Chitale, Dhananjay A / Williamson, Sean R / Rundle, Andrew G / Rybicki, Benjamin A

    Cancer medicine

    2024  Volume 13, Issue 6, Page(s) e7118

    Abstract: Backround: Inflammation characterized by the presence of T and B cells is often observed in prostate cancer, but it is unclear how T- and B-cell levels change during carcinogenesis and whether such changes influence disease progression.: Methods: The ...

    Abstract Backround: Inflammation characterized by the presence of T and B cells is often observed in prostate cancer, but it is unclear how T- and B-cell levels change during carcinogenesis and whether such changes influence disease progression.
    Methods: The study used a retrospective sample of 73 prostate cancer cases (45 whites and 28 African Americans) that underwent surgery as their primary treatment and had a benign prostate biopsy at least 1 year before diagnosis. CD3+, CD4+, and CD20+ lymphocytes were quantified by immunohistochemistry in paired pre- and post-diagnostic benign prostate biopsy and tumor surgical specimens, respectively. Clusters of similar trends of expression across two different timepoints and three distinct prostate regions-benign biopsy glands (BBG), tumor-adjacent benign glands (TAG), and malignant tumor glandular (MTG) regions-were identified using Time-series Anytime Density Peaks Clustering (TADPole). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of time to biochemical recurrence associated with region-specific lymphocyte counts and regional trends.
    Results: The risk of biochemical recurrence was significantly reduced in men with an elevated CD20+ count in TAG (HR = 0.81, p = 0.01) after adjusting for covariates. Four distinct patterns of expression change across the BBG-TAG-MTG regions were identified for each marker. For CD20+, men with low expression in BBG and higher expression in TAG compared to MTG had an adjusted HR of 3.06 (p = 0.03) compared to the reference group that had nominal differences in CD20+ expression across all three regions. The two CD3+ expression patterns that featured lower CD3+ expression in the BBG compared to the TAG and MTG regions had elevated HRs ranging from 3.03 to 4.82 but did not reach statistical significance.
    Conclusions: Longitudinal and spatial expression patterns of both CD3+ and CD20+ suggest that increased expression in benign glands during prostate carcinogenesis is associated with an aggressive disease course.
    MeSH term(s) Male ; Humans ; Prostate/surgery ; Prostate/pathology ; Retrospective Studies ; Prostatic Neoplasms/surgery ; Prostatic Neoplasms/pathology ; B-Lymphocytes/pathology ; Carcinogenesis/pathology
    Language English
    Publishing date 2024-03-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2659751-2
    ISSN 2045-7634 ; 2045-7634
    ISSN (online) 2045-7634
    ISSN 2045-7634
    DOI 10.1002/cam4.7118
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  5. Article ; Online: Inclusivity in Research Matters: Variants in

    Garman, Lori / Pezant, Nathan / Dawkins, Bryan A / Rasmussen, Astrid / Levin, Albert M / Rybicki, Benjamin A / Iannuzzi, Michael C / Bagavant, Harini / Deshmukh, Umesh S / Montgomery, Courtney G

    American journal of respiratory and critical care medicine

    2023  Volume 209, Issue 1, Page(s) 106–109

    MeSH term(s) Humans ; Black People/genetics ; Pulmonary Fibrosis/genetics
    Chemical Substances PVT1 long-non-coding RNA, human
    Language English
    Publishing date 2023-01-29
    Publishing country United States
    Document type Letter
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.202210-1969LE
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  6. Article ; Online: Identification of Environmental Exposures Associated with Risk of Sarcoidosis in African Americans.

    Levin, Albert M / She, Ruicong / Chen, Yalei / Adrianto, Indra / Datta, Indrani / Loveless, Ian M / Garman, Lori / Montgomery, Courtney G / Li, Jia / Iannuzzi, Michael C / Rybicki, Benjamin A

    Annals of the American Thoracic Society

    2023  Volume 20, Issue 9, Page(s) 1274–1282

    Abstract: Rationale: ...

    Abstract Rationale:
    MeSH term(s) Humans ; Black or African American ; Sarcoidosis/epidemiology ; Sarcoidosis/genetics ; Black People ; Environmental Exposure/adverse effects
    Language English
    Publishing date 2023-05-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2717461-X
    ISSN 2325-6621 ; 1943-5665 ; 2325-6621
    ISSN (online) 2325-6621 ; 1943-5665
    ISSN 2325-6621
    DOI 10.1513/AnnalsATS.202208-722OC
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  7. Article ; Online: Granuloma genes in sarcoidosis: what is new?

    Fischer, Annegret / Rybicki, Benjamin A

    Current opinion in pulmonary medicine

    2015  Volume 21, Issue 5, Page(s) 510–516

    Abstract: Purpose of review: Nonnecrotizing granulomas in the affected organ are the hallmark of sarcoidosis. This review summarizes most recent genetic findings in sarcoidosis with a focus on genes that might influence granuloma formation or resolution. Specific ...

    Abstract Purpose of review: Nonnecrotizing granulomas in the affected organ are the hallmark of sarcoidosis. This review summarizes most recent genetic findings in sarcoidosis with a focus on genes that might influence granuloma formation or resolution. Specific results in multiple ethnic groups and certain clinical subphenotypes, such as extra-pulmonary organ involvement, are discussed.
    Recent findings: Associations of genetic variants in antigen-presenting molecules (HLA-DRB1) were shown to confer risk to sarcoidosis and certain disease phenotypes in populations of different ethnic origins. Specific DRB1 alleles, such as *0301 and *0302, appear to confer protection against chronic disease, but in an ethnic-specific manner illustrating the extensive genetic heterogeneity and complexity at this locus. Mechanistic studies of putative sarcoid antigens lend further credence to a role of HLA-DRB1 in disease pathogenesis. With relevance to granuloma formation, genes involved in apoptotic processes and immune cell activation were further confirmed (ANXA11 and BTNL2) in multiple ethnicities; others were newly identified (XAF1). Linking mechanism to clinical application, a TNF variant was shown to correlate with anti-TNF response in sarcoidosis patients.
    Summary: The investigation of known and novel risk variants for sarcoidosis and specific clinical phenotypes in various ethnicities highlights the genetic complexity of the disease. Detailed subanalysis of disease phenotypes revealed the potential for prediction of extra-pulmonary organ involvement and therapy response based on the patient's genotype.
    MeSH term(s) Alleles ; Granuloma/genetics ; Granuloma/pathology ; HLA-DRB1 Chains/genetics ; Humans ; Lymphocyte Activation ; Sarcoidosis/genetics ; Sarcoidosis/pathology ; T-Lymphocytes/immunology ; Tumor Necrosis Factor-alpha/genetics
    Chemical Substances HLA-DRB1 Chains ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2015-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1285505-4
    ISSN 1531-6971 ; 1070-5287 ; 1078-1641
    ISSN (online) 1531-6971
    ISSN 1070-5287 ; 1078-1641
    DOI 10.1097/MCP.0000000000000189
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  8. Article ; Online: Convolutional Neural Network Quantification of Gleason Pattern 4 and Association With Biochemical Recurrence in Intermediate-Grade Prostate Tumors.

    Chen, Yalei / Loveless, Ian M / Nakai, Tiffany / Newaz, Rehnuma / Abdollah, Firas F / Rogers, Craig G / Hassan, Oudai / Chitale, Dhananjay / Arora, Kanika / Williamson, Sean R / Gupta, Nilesh S / Rybicki, Benjamin A / Sadasivan, Sudha M / Levin, Albert M

    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

    2023  Volume 36, Issue 7, Page(s) 100157

    Abstract: Differential classification of prostate cancer grade group (GG) 2 and 3 tumors remains challenging, likely because of the subjective quantification of the percentage of Gleason pattern 4 (%GP4). Artificial intelligence assessment of %GP4 may improve its ... ...

    Abstract Differential classification of prostate cancer grade group (GG) 2 and 3 tumors remains challenging, likely because of the subjective quantification of the percentage of Gleason pattern 4 (%GP4). Artificial intelligence assessment of %GP4 may improve its accuracy and reproducibility and provide information for prognosis prediction. To investigate this potential, a convolutional neural network (CNN) model was trained to objectively identify and quantify Gleason pattern (GP) 3 and 4 areas, estimate %GP4, and assess whether CNN-predicted %GP4 is associated with biochemical recurrence (BCR) risk in intermediate-risk GG 2 and 3 tumors. The study was conducted in a radical prostatectomy cohort (1999-2012) of African American men from the Henry Ford Health System (Detroit, Michigan). A CNN model that could discriminate 4 tissue types (stroma, benign glands, GP3 glands, and GP4 glands) was developed using histopathologic images containing GG 1 (n = 45) and 4 (n = 20) tumor foci. The CNN model was applied to GG 2 (n = 153) and 3 (n = 62) tumors for %GP4 estimation, and Cox proportional hazard modeling was used to assess the association of %GP4 and BCR, accounting for other clinicopathologic features including GG. The CNN model achieved an overall accuracy of 86% in distinguishing the 4 tissue types. Furthermore, CNN-predicted %GP4 was significantly higher in GG 3 than in GG 2 tumors (P = 7.2 × 10
    MeSH term(s) Male ; Humans ; Artificial Intelligence ; Reproducibility of Results ; Prostatic Neoplasms/pathology ; Neoplasm Grading ; Prostatectomy ; Neural Networks, Computer ; Neoplasm Recurrence, Local
    Chemical Substances GP 4 (81746-15-8)
    Language English
    Publishing date 2023-03-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 645073-8
    ISSN 1530-0285 ; 0893-3952
    ISSN (online) 1530-0285
    ISSN 0893-3952
    DOI 10.1016/j.modpat.2023.100157
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  9. Article ; Online: Prostate-specific antigen testing after the US Preventive Services Task Force recommendation: a population-based analysis of electronic health data.

    Frendl, Daniel M / Epstein, Mara M / Fouayzi, Hassan / Krajenta, Richard / Rybicki, Benjamin A / Sokoloff, Mitchell H

    Cancer causes & control : CCC

    2020  Volume 31, Issue 9, Page(s) 861–867

    Abstract: Purpose: This study describes longitudinal trends in the use of prostate-specific antigen (PSA)-based testing in two geographically distinct healthcare systems following the 2011 US Preventive Services Task Force (USPSTF) recommendations against routine ...

    Abstract Purpose: This study describes longitudinal trends in the use of prostate-specific antigen (PSA)-based testing in two geographically distinct healthcare systems following the 2011 US Preventive Services Task Force (USPSTF) recommendations against routine PSA screening.
    Methods: We analyzed population-based health claims data from 253,139 men aged 40-80 who were enrolled at two US healthcare systems. We assessed trends in the percentage of eligible men receiving ≥ 1 PSA test per year by time period (2000-2008, 2009-2011, 2012-2014), age (40-54, 55-69, 70-80), and race (white, black, other, unknown), and conducted a joinpoint regression analysis.
    Results: Men aged 55-69 and 70-80 years of all races had similar use of PSA testing between 2000 and 2011, ranging between 47 and 56% of eligible men by year, while only 22-26% of men aged 40-54 had a PSA test per year during this period. Overall, the percentage of men receiving at least one PSA test per year decreased by 26% between 2009-2011 and 2012-2014, with similar trends across race and age groups. PSA testing declined significantly after 2011 (annual percent change = - 11.28).
    Conclusions: Following the 2011 USPSTF recommendations against routine PSA screening, declines in PSA testing were observed among men of all races and across all age groups in two large US healthcare systems.
    MeSH term(s) Adult ; Advisory Committees ; Age Factors ; Aged ; Aged, 80 and over ; Early Detection of Cancer/statistics & numerical data ; Electronic Health Records/statistics & numerical data ; Guideline Adherence ; Humans ; Kallikreins/analysis ; Longitudinal Studies ; Male ; Massachusetts/epidemiology ; Michigan/epidemiology ; Middle Aged ; Preventive Health Services/statistics & numerical data ; Prostate-Specific Antigen/analysis ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/epidemiology ; Regression Analysis ; United States/epidemiology
    Chemical Substances KLK3 protein, human (EC 3.4.21.-) ; Kallikreins (EC 3.4.21.-) ; Prostate-Specific Antigen (EC 3.4.21.77)
    Language English
    Publishing date 2020-06-17
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1064022-8
    ISSN 1573-7225 ; 0957-5243
    ISSN (online) 1573-7225
    ISSN 0957-5243
    DOI 10.1007/s10552-020-01324-x
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  10. Article: Sex differences in the genetics of sarcoidosis across European and African ancestry populations.

    Xiong, Ying / Kullberg, Susanna / Garman, Lori / Pezant, Nathan / Ellinghaus, David / Vasila, Vasiliki / Eklund, Anders / Rybicki, Benjamin A / Iannuzzi, Michael C / Schreiber, Stefan / Müller-Quernheim, Joachim / Montgomery, Courtney G / Grunewald, Johan / Padyukov, Leonid / Rivera, Natalia V

    Frontiers in medicine

    2023  Volume 10, Page(s) 1132799

    Abstract: Background: Sex differences in the susceptibility of sarcoidosis are unknown. The study aims to identify sex-dependent genetic variations in two clinical sarcoidosis phenotypes: Löfgren's syndrome (LS) and non-Löfgren's syndrome (non-LS).: Methods: A ...

    Abstract Background: Sex differences in the susceptibility of sarcoidosis are unknown. The study aims to identify sex-dependent genetic variations in two clinical sarcoidosis phenotypes: Löfgren's syndrome (LS) and non-Löfgren's syndrome (non-LS).
    Methods: A meta-analysis of genome-wide association studies was conducted on Europeans and African Americans, totaling 10,103 individuals from three population-based cohorts, Sweden (
    Results: We identified sex-dependent genetic variations in LS and non-LS sex groups. Genetic findings in LS sex groups were explicitly located in the extended Major Histocompatibility Complex (xMHC). In non-LS, genetic differences in the sex groups were primarily located in the MHC class II subregion and
    Conclusion: Our findings provide new evidence for a sex bias underlying sarcoidosis genetic architecture, particularly in clinical phenotypes LS and non-LS. Biological sex likely plays a role in disease mechanisms in sarcoidosis.
    Language English
    Publishing date 2023-05-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2023.1132799
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