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  1. Article ; Online: MIR448 antagomir reduces arrhythmic risk after myocardial infarction by upregulating the cardiac sodium channel

    Gyeoung-Jin Kang / An Xie / Hong Liu / Samuel C. Dudley Jr.

    JCI Insight, Vol 5, Iss

    2020  Volume 23

    Abstract: Cardiac ischemia is associated with arrhythmias; however, effective therapies are currently limited. The cardiac voltage-gated sodium channel α subunit (SCN5A), encoding the Nav1.5 current, plays a key role in the cardiac electrical conduction and ... ...

    Abstract Cardiac ischemia is associated with arrhythmias; however, effective therapies are currently limited. The cardiac voltage-gated sodium channel α subunit (SCN5A), encoding the Nav1.5 current, plays a key role in the cardiac electrical conduction and arrhythmic risk. Here, we show that hypoxia reduces Nav1.5 through effects on a miR, miR-448. miR-448 expression is increased in ischemic cardiomyopathy. miR-448 has a conserved binding site in 3′-UTR of SCN5A. miR-448 binding to this site suppressed SCN5A expression and sodium currents. Hypoxia-induced HIF-1α and NF-κB were major transcriptional regulators for MIR448. Moreover, hypoxia relieved MIR448 transcriptional suppression by RE1 silencing transcription factor. Therefore, miR-448 inhibition reduced arrhythmic risk after myocardial infarction. Here, we show that ischemia drove miR-448 expression, reduced Nav1.5 current, and increased arrhythmic risk. Arrhythmic risk was improved by preventing Nav1.5 downregulation, suggesting a new approach to antiarrhythmic therapy.
    Keywords Cardiology ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: DeepLiverNet: a deep transfer learning model for classifying liver stiffness using clinical and T2-weighted magnetic resonance imaging data in children and young adults.

    Li, Hailong / He, Lili / Dudley, Jonathan A / Maloney, Thomas C / Somasundaram, Elanchezhian / Brady, Samuel L / Parikh, Nehal A / Dillman, Jonathan R

    Pediatric radiology

    2020  Volume 51, Issue 3, Page(s) 392–402

    Abstract: Background: Although MR elastography allows for quantitative evaluation of liver stiffness to assess chronic liver diseases, it has associated drawbacks related to additional scanning time, patient discomfort, and added costs.: Objective: To develop ... ...

    Abstract Background: Although MR elastography allows for quantitative evaluation of liver stiffness to assess chronic liver diseases, it has associated drawbacks related to additional scanning time, patient discomfort, and added costs.
    Objective: To develop a machine learning model that can categorically classify the severity of liver stiffness using both anatomical T2-weighted MRI and clinical data for children and young adults with known or suspected pediatric chronic liver diseases.
    Materials and methods: We included 273 subjects with known or suspected chronic liver disease. We extracted data including axial T2-weighted fast spin-echo fat-suppressed images, clinical data (e.g., demographic/anthropomorphic data, particular medical diagnoses, laboratory values) and MR elastography liver stiffness measurements. We propose DeepLiverNet (a deep transfer learning model) to classify patients into one of two groups: no/mild liver stiffening (<3 kPa) or moderate/severe liver stiffening (≥3 kPa). We conducted internal cross-validation using 178 subjects, and external validation using an independent cohort of 95 subjects. We assessed diagnostic performance using accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AuROC).
    Results: In the internal cross-validation experiment, the combination of clinical and imaging data produced the best performance (AuROC=0.86) compared to clinical (AuROC=0.83) or imaging (AuROC=0.80) data alone. Using both clinical and imaging data, the DeepLiverNet correctly classified patients with accuracy of 88.0%, sensitivity of 74.3% and specificity of 94.6%. In our external validation experiment, this same deep learning model achieved an accuracy of 80.0%, sensitivity of 61.1%, specificity of 91.5% and AuROC of 0.79.
    Conclusion: A deep learning model that incorporates clinical data and anatomical T2-weighted MR images might provide a means of risk-stratifying liver stiffness and directing the use of MR elastography.
    MeSH term(s) Child ; Elasticity Imaging Techniques ; Humans ; Liver/diagnostic imaging ; Liver Diseases/diagnostic imaging ; Machine Learning ; Magnetic Resonance Imaging ; Young Adult
    Language English
    Publishing date 2020-10-13
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 124459-0
    ISSN 1432-1998 ; 0301-0449
    ISSN (online) 1432-1998
    ISSN 0301-0449
    DOI 10.1007/s00247-020-04854-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Rates of Ipsilateral Local-regional Recurrence in High-risk Patients Undergoing Immediate Post-mastectomy Reconstruction (AFT-01).

    Dudley, Christina M / Wiener, Alyssa A / Stankowski-Drengler, Trista J / Schumacher, Jessica R / Francescatti, Amanda B / Poore, Samuel O / Greenberg, Caprice C / Neuman, Heather B

    Clinical breast cancer

    2021  Volume 21, Issue 5, Page(s) 433–439

    Abstract: Background: Some surgeons remain hesitant to perform immediate breast reconstruction (IBR) in patients with higher risk cancers owing to concerns about cancer recurrence and/or detection. Our objective was to determine the rate of ipsilateral local- ... ...

    Abstract Background: Some surgeons remain hesitant to perform immediate breast reconstruction (IBR) in patients with higher risk cancers owing to concerns about cancer recurrence and/or detection. Our objective was to determine the rate of ipsilateral local-regional recurrence for stage II/III patients who underwent IBR.
    Methods: The National Cancer Database special study mechanism was used to create a stratified sample of women diagnosed with stage II/III breast cancer from 1217 facilities. Demographic, tumor, and recurrence data for women who underwent mastectomy with or without IBR were abstracted, including location of recurrence and method of detection. Estimates of 5-year local-regional recurrence rates were calculated and factors associated with recurrence were identified with multivariable Cox regression.
    Results: Some 13% (692/5318) of stage II/III patients underwent IBR after mastectomy. Patients undergoing IBR were younger (P < .001), with fewer comorbid conditions (P < .001), and with lower tumor burden in the breast (P = .001) and the lymph nodes (P = 0.01). The 5-year rate of ipsilateral local-regional recurrence was 3.6% with no significant difference between patients with or without IBR (3.0% vs. 3.7%, P = .4). Most recurrences were detected by the patient (45%) or on physician examination (24%). Reconstruction was not associated with recurrence on multivariable analysis (hazard ratio = 0.83, P = .52).
    Conclusion: Women with stage II/III breast cancer selected for IBR had similar rates of ipsilateral local-regional recurrence compared with those undergoing mastectomy alone. Offering IBR after mastectomy in a patient-centered manner to select patients with stage II/III breast cancer is an acceptable consideration.
    MeSH term(s) Adult ; Breast Neoplasms/mortality ; Breast Neoplasms/surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Mastectomy/adverse effects ; Mastectomy/methods ; Mastectomy/mortality ; Middle Aged ; Neoplasm Recurrence, Local/mortality ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/prevention & control ; Risk Factors
    Language English
    Publishing date 2021-03-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2106734-X
    ISSN 1938-0666 ; 1526-8209
    ISSN (online) 1938-0666
    ISSN 1526-8209
    DOI 10.1016/j.clbc.2021.03.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Machine Learning Prediction of Liver Stiffness Using Clinical and T2-Weighted MRI Radiomic Data.

    He, Lili / Li, Hailong / Dudley, Jonathan A / Maloney, Thomas C / Brady, Samuel L / Somasundaram, Elanchezhian / Trout, Andrew T / Dillman, Jonathan R

    AJR. American journal of roentgenology

    2019  Volume 213, Issue 3, Page(s) 592–601

    Abstract: OBJECTIVE. ...

    Abstract OBJECTIVE.
    MeSH term(s) Adolescent ; Child ; Elasticity Imaging Techniques ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Liver Diseases/diagnostic imaging ; Liver Diseases/pathology ; Machine Learning ; Magnetic Resonance Imaging/methods ; Male ; Young Adult
    Language English
    Publishing date 2019-05-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 82076-3
    ISSN 1546-3141 ; 0361-803X ; 0092-5381
    ISSN (online) 1546-3141
    ISSN 0361-803X ; 0092-5381
    DOI 10.2214/AJR.19.21082
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Dermatitis herpetiformis bodies and autoantibodies to noncutaneous organs and mitochondria in dermatitis herpetiformis

    Ana Maria Abreu Velez / Hong Yi / Julia Griffin Girard / Zhe Jiao / Mauricio Duque Ramírez / Luis F. Arias / Bruce B. Smoller / Samuel C. Dudley Jr / Michael S. Howard

    Our Dermatology Online, Vol 3, Iss 4, Pp 283-

    2012  Volume 291

    Abstract: Introduction: The precise nature of the previously described dermatitis herpetiformis bodies remains unknown.Aims: Our study was conducted to investigate the nature of dermatitis herpetiformis bodies in the skin in 7 cases of dermatitis herpetiformis, ... ...

    Abstract Introduction: The precise nature of the previously described dermatitis herpetiformis bodies remains unknown.Aims: Our study was conducted to investigate the nature of dermatitis herpetiformis bodies in the skin in 7 cases of dermatitis herpetiformis, and to search for the presence of autoantibodies in other organsMethods: We utilized clinical, histopathologic, and immunologic methods to evaluate these patients.Results: Dermatitis herpetiformis bodies were found to be comprised of an amalgamation of immunoglobulins A and M, as well as molecules reactive with antibodies to armadillo repeat gene deleted in velo-cardio-facial syndrome, desmoplakins 1 and 2, and plakophilin 4. In addition, we found immunologic colocalization with selected autoantibodies associated with mitochondria in the skin, heart, kidney, and peripheral nerves. The dermatitis herpetiformis bodies did not demonstrate immunologic colocalization with tissue/epidermal transglutaminase.Conclusion: The complete biochemical nature of dermatitis herpetiformis bodies requires further characterization. Dermatitis herpetiformis bodies in these patients appear to be distinctly different than cytoid bodies. Further studies are required to determine if the antibodies to noncutaneous organs are pathogenic, and/or contribute to systemic morbility in dermatitis herpetiformis patients.
    Keywords adermatitis herpetiformis ; endomysium ; mitochondria ; plakophilins ; p120 ctn molecules ; desmoplakins ; Dermatology ; RL1-803 ; Medicine ; R ; DOAJ:Dermatology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 610
    Language English
    Publishing date 2012-10-01T00:00:00Z
    Publisher Our Dermatology Online
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Ion channel messenger RNA processing defects and arrhythmia

    Zhou A / Dudley Jr SC

    Current Biomarker Findings, Vol 2014, Iss default, Pp 151-

    2014  Volume 160

    Abstract: Anyu Zhou, Samuel C Dudley Jr Lifespan Cardiovascular Research Center, The Warren Alpert School ...

    Abstract Anyu Zhou, Samuel C Dudley Jr Lifespan Cardiovascular Research Center, The Warren Alpert School of Medicine, Brown University, and Providence Veterans Administration Medical Center, Providence, RI, USA Abstract: Messenger RNA (mRNA) processing is an essential step for the expression of most eukaryote genes. Ion channels are critical for proper electrical activity in the heart, and perturbations of these channels are known to cause arrhythmia. Recently, mRNA processing defects have been shown to contribute to altered ion channel activity and arrhythmogenesis. Abnormal pre-mRNA splicing of cardiac ion channels, including the cardiac sodium channel, potassium channels, and calcium channels, because of mutations of the cis-elements within the RNA or abnormal expression of splicing factors, has been documented to contribute to arrhythmic risk. In addition to pre-mRNA splicing, other mRNA processing events, such as 3'-end formation and mRNA turnover, are also disrupted in cardiac diseases, such as congenital heart disease caused by mutation at the 3'-untranslated region of GATA4. mRNA stability is also dysregulated by altered expression of microRNAs in atrial fibrillation. In this review, we discuss our current understanding of how mRNA processing defects contribute to the risk of arrhythmias and how monitoring the products of abnormal processing may lead to diagnostic tests for arrhythmic risk. Keywords: messenger RNA, arrhythmia, sudden death, ion channels, biomarkers
    Keywords Biology (General) ; QH301-705.5 ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2014-11-01T00:00:00Z
    Publisher Dove Medical Press
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Determination of ebselen-sensitive reactive oxygen metabolites (ebROM) in human serum based upon N,N'-diethyl-1,4-phenylenediamine oxidation.

    Liang, Yongliang / Roede, James R / Dikalov, Sergey / Miller, Nana Gletsu / Dudley, Samuel C / Quyyumi, Arshed / Jones, Dean P

    Clinica chimica acta; international journal of clinical chemistry

    2012  Volume 414, Page(s) 1–6

    Abstract: Background: Oxidative stress occurs through free radical- and non-radical-mediated oxidative mechanisms, but these are poorly discriminated by most assays. A convenient assay for oxidants in human serum is based upon the Fe(2+)-dependent decomposition ... ...

    Abstract Background: Oxidative stress occurs through free radical- and non-radical-mediated oxidative mechanisms, but these are poorly discriminated by most assays. A convenient assay for oxidants in human serum is based upon the Fe(2+)-dependent decomposition of peroxides to oxidize N,N'-diethyl-1,4-phenylenediamine (DEPPD) to a stable radical cation which can be measured spectrophotometrically.
    Methods: We investigated modification of the DEPPD oxidation assay to discriminate color formation due to non-radical oxidants, including hydroperoxides and endoperoxides, which are sensitive to ebselen.
    Results: Use of serum, which has been pretreated with ebselen as a reference, provides a quantitative assay for non-radical, reactive oxidant species in serum, including hydroperoxides, endoperoxides and epoxides. In a set of 35 human serum samples, non-radical oxidants largely accounted for DEPPD oxidation in 86% of the samples while the remaining 14% had considerable contribution from other redox-active chemicals.
    Conclusions: The simple modification in which ebselen-pretreated sample is used as a reference provides means to quantify non-radical oxidants in human serum. Application of this approach could enhance understanding of the contribution of different types of oxidative stress to disease.
    MeSH term(s) Azoles/blood ; Humans ; Molecular Structure ; Organoselenium Compounds/blood ; Oxidation-Reduction ; Oxidative Stress ; Oxygen/blood ; Oxygen/metabolism ; Phenylenediamines/blood ; Phenylenediamines/chemistry ; Phenylenediamines/metabolism
    Chemical Substances Azoles ; Organoselenium Compounds ; Phenylenediamines ; ebselen (40X2P7DPGH) ; Oxygen (S88TT14065)
    Language English
    Publishing date 2012-06-08
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80228-1
    ISSN 1873-3492 ; 0009-8981
    ISSN (online) 1873-3492
    ISSN 0009-8981
    DOI 10.1016/j.cca.2012.06.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Long-term survival after successful inhospital cardiac arrest resuscitation.

    Bloom, Heather L / Shukrullah, Irfan / Cuellar, Jose R / Lloyd, Michael S / Dudley, Samuel C / Zafari, A Maziar

    American heart journal

    2007  Volume 153, Issue 5, Page(s) 831–836

    Abstract: Background: Little is known about long-term outcomes of patients who survive inhospital cardiac arrest.: Methods: We examined long-term survival after inhospital cardiac arrest and whether procedural changes that improved survival to discharge ... ...

    Abstract Background: Little is known about long-term outcomes of patients who survive inhospital cardiac arrest.
    Methods: We examined long-term survival after inhospital cardiac arrest and whether procedural changes that improved survival to discharge impacted long-term survival. Consecutive inhospital arrests in the Atlanta Veterans Affairs Medical Center (Atlanta, GA) from 1995 to 2004 (n = 732) were retrospectively analyzed. Data regarding the arrest was obtained, including age, left ventricular ejection fraction, medications, and comorbidities, presenting rhythm, location of arrest, code duration, and outcomes. Long-term mortality data was obtained based on chart and Social Security Death Index reviews. Further data was gathered on internal cardioverter-defibrillator presence and use in survivors.
    Results: Overall, 49 subjects (6.6%) survived to discharge. Univariate analysis found that ventricular tachycardia/ventricular fibrillation and the use of beta-blockers, angiotensin-converting enzyme inhibitors, and antiarrhythmics at the time of arrest were associated with increased survival, whereas advancing age and comorbidities were associated with a higher risk of mortality. Multivariate analysis determined that age, rhythm, and comorbidities independently affected survival. Implementation of a resuscitation program previously documented to improve survival to discharge did not translate to durable long-term survival. Three-year survival rate after discharge was only 41%. Alternatively, subjects with internal cardioverter-defibrillator showed a 36% improvement in 3-year survival rate to 77% (P = .001).
    Conclusions: Subjects with inhospital cardiac arrest have poor long-term prognoses. A strategy that improved inhospital survival did not alter long-term mortality rate. Thus, survival to discharge may not be a sufficient end point for future resuscitation trials.
    MeSH term(s) Aged ; Cardiopulmonary Resuscitation/statistics & numerical data ; Cognition Disorders/epidemiology ; Comorbidity ; Defibrillators, Implantable/statistics & numerical data ; Georgia/epidemiology ; Heart Arrest/mortality ; Heart Arrest/therapy ; Hospitalization/statistics & numerical data ; Humans ; Longitudinal Studies ; Middle Aged ; Retrospective Studies ; Survival Analysis ; Survivors/statistics & numerical data ; Treatment Outcome
    Language English
    Publishing date 2007-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80026-0
    ISSN 1097-6744 ; 0002-8703
    ISSN (online) 1097-6744
    ISSN 0002-8703
    DOI 10.1016/j.ahj.2007.02.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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