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  1. Article ; Online: Interpretable and context-free deconvolution of multi-scale whole transcriptomic data with UniCell deconvolve.

    Charytonowicz, Daniel / Brody, Rachel / Sebra, Robert

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 1350

    Abstract: We introduce UniCell: Deconvolve Base (UCDBase), a pre-trained, interpretable, deep learning model to deconvolve cell type fractions and predict cell identity across Spatial, bulk-RNA-Seq, and scRNA-Seq datasets without contextualized reference data. UCD ...

    Abstract We introduce UniCell: Deconvolve Base (UCDBase), a pre-trained, interpretable, deep learning model to deconvolve cell type fractions and predict cell identity across Spatial, bulk-RNA-Seq, and scRNA-Seq datasets without contextualized reference data. UCD is trained on 10 million pseudo-mixtures from a fully-integrated scRNA-Seq training database comprising over 28 million annotated single cells spanning 840 unique cell types from 898 studies. We show that our UCDBase and transfer-learning models achieve comparable or superior performance on in-silico mixture deconvolution to existing, reference-based, state-of-the-art methods. Feature attribute analysis uncovers gene signatures associated with cell-type specific inflammatory-fibrotic responses in ischemic kidney injury, discerns cancer subtypes, and accurately deconvolves tumor microenvironments. UCD identifies pathologic changes in cell fractions among bulk-RNA-Seq data for several disease states. Applied to lung cancer scRNA-Seq data, UCD annotates and distinguishes normal from cancerous cells. Overall, UCD enhances transcriptomic data analysis, aiding in assessment of cellular and spatial context.
    MeSH term(s) Transcriptome ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; Gene Expression Profiling/methods ; RNA-Seq/methods
    Language English
    Publishing date 2023-03-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-36961-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cognitive Testing of an Electronic Consent Platform: Researcher Perspectives.

    Robins, Daniel / Brody, Rachel / Parvanova, Irena / Finkelstein, Joseph

    Studies in health technology and informatics

    2021  Volume 284, Page(s) 457–462

    Abstract: This study focuses on feedback from domain experts to assess usability and acceptance of the E-Consent electronic consent platform. Quantitative and qualitative data were captured throughout the usability inspection, which was structured around a ... ...

    Abstract This study focuses on feedback from domain experts to assess usability and acceptance of the E-Consent electronic consent platform. Quantitative and qualitative data were captured throughout the usability inspection, which was structured around a cognitive walkthrough with heuristics evaluation. Additional surveys measured biobanking knowledge and attitudes and familiarity with informed consent. A semi-structured qualitative interview captured open-ended feedback. 23 researchers of various ages and job titles were included for analysis. The System Usability Scale (SUS) provided a standardized reference for usability and satisfaction, and the mean result of 86.7 corresponds with an 'above average' usability rating in the >90th percentile. Overall, participants believe that electronic consenting using this platform will be faster than previous workflows while enhancing patient understanding, and human rapport is still a key component of the consent process. Expert review has provided valuable insight and actionable information that will be used to further enhance this maturing platform.
    MeSH term(s) Biological Specimen Banks ; Data Accuracy ; Electronics ; Humans ; Informed Consent ; Neuropsychological Tests
    Language English
    Publishing date 2021-07-31
    Publishing country Netherlands
    Document type Journal Article
    ISSN 1879-8365
    ISSN (online) 1879-8365
    DOI 10.3233/SHTI210772
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Discovery of a multipotent cell type from the term human placenta.

    Vadakke-Madathil, Sangeetha / Wang, Bingyan J / Oniskey, Micayla / Dekio, Fumiko / Brody, Rachel / Gelber, Shari / Sperling, Rhoda / Chaudhry, Hina W

    bioRxiv : the preprint server for biology

    2024  

    Abstract: We report a unique population of multipotent cells isolated from the term human placenta, for the first time, that can differentiate into cardiomyocytes and vascular cells with clonal proliferative ability, migratory ability, and trancriptomic evidence ... ...

    Abstract We report a unique population of multipotent cells isolated from the term human placenta, for the first time, that can differentiate into cardiomyocytes and vascular cells with clonal proliferative ability, migratory ability, and trancriptomic evidence of immune privilege. Caudal-type homeobox-2 (CDX2) is a conserved factor that regulates trophectoderm formation and placentation during early embryonic development but has not previously been implicated in developmentally conserved regenerative mechanisms. We had earlier reported that Cdx2 lineage cells in the mouse placenta are capable of restoring cardiac function after intravenous delivery in male mice with experimental cardiac injury (myocardial infarction). Here we demonstrate that CDX2-expressing cells are prevalent in the human chorion and are poised for cardiovascular differentiation. We examined the term placentas from 106 healthy patients and showed that isolated CDX2 cells can spontaneously differentiate into cardiomyocytes, functional vascular cells, and retain homing ability
    Language English
    Publishing date 2024-01-13
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.08.02.551028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: HIF-1α Cardioprotection in COVID-19 Patients.

    Wang, Bingyan J / Vadakke-Madathil, Sangeetha / Croft, Lori B / Brody, Rachel I / Chaudhry, Hina W

    JACC. Basic to translational science

    2022  Volume 7, Issue 1, Page(s) 67–69

    Language English
    Publishing date 2022-01-24
    Publishing country United States
    Document type Journal Article
    ISSN 2452-302X
    ISSN (online) 2452-302X
    DOI 10.1016/j.jacbts.2021.12.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: TERT and BRAF V600E mutations in thyroid cancer of World Trade Center Responders.

    van Gerwen, Maaike / Cerutti, Janete Maria / Mendes, Thais Biude / Brody, Rachel / Genden, Eric / Riggins, Gregory J / Taioli, Emanuela

    Carcinogenesis

    2023  Volume 44, Issue 4, Page(s) 350–355

    Abstract: The 2-fold excess thyroid cancer risk reported in multiple World Trade Center (WTC) disaster exposed cohorts cannot entirely be explained by surveillance and physician bias thus highlighting the need to investigate the potential consequences of the dust ... ...

    Abstract The 2-fold excess thyroid cancer risk reported in multiple World Trade Center (WTC) disaster exposed cohorts cannot entirely be explained by surveillance and physician bias thus highlighting the need to investigate the potential consequences of the dust exposure, containing carcinogenic and endocrine disruptive elements, on the thyroid. This study investigated the presence of TERT promoter and BRAF V600E mutations in 20 WTC-exposed versus 23 matched non-exposed thyroid cancers as potential mechanism explaining the excess risk. Although no significant difference in BRAF V600E mutation was found, TERT promoter mutations were significantly more prevalent in WTC thyroid cancer versus non-exposed thyroid cancers (P = 0.021). The odds of a TERT promoter mutation was significantly higher in the WTC versus the non-WTC thyroid cancers after adjustment [ORadj: 7.11 (95% CI: 1.21-41.83)]. These results may indicate that exposure to the mixture of pollutants present in the WTC dust resulted in an excess thyroid cancer risk and potentially more aggressive thyroid cancer, warranting investigating WTC responders on thyroid-associated symptoms during their health checkups. Future studies should include long-term follow-up to provide important insights in whether thyroid-specific survival is negatively affected by WTC dust exposure and whether this is because of the presence of one or more driver mutations.
    MeSH term(s) Humans ; Proto-Oncogene Proteins B-raf/genetics ; Thyroid Cancer, Papillary/genetics ; Thyroid Neoplasms/etiology ; Thyroid Neoplasms/genetics ; Promoter Regions, Genetic ; Telomerase/genetics ; Mutation
    Chemical Substances Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Telomerase (EC 2.7.7.49) ; TERT protein, human (EC 2.7.7.49) ; BRAF protein, human (EC 2.7.11.1)
    Language English
    Publishing date 2023-05-05
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 603134-1
    ISSN 1460-2180 ; 0143-3334
    ISSN (online) 1460-2180
    ISSN 0143-3334
    DOI 10.1093/carcin/bgad029
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Microultrasound in the detection of the index lesion in prostate cancer.

    Pedraza, Adriana M / Gupta, Raghav / Musheyev, David / Pino, Tanisha / Shah, Akash / Brody, Rachel / Wagaskar, Vinayak / Kaufmann, Basil / Gorin, Michael A / Menon, Mani / Tewari, Ashutosh

    The Prostate

    2023  Volume 84, Issue 1, Page(s) 79–86

    Abstract: Introduction and objective: The natural progression of prostate cancer is primarily driven by an index lesion (IL). Studies have shown that different metastases within the same patient arise from a single precursor cell. Therefore, our aim is to assess ... ...

    Abstract Introduction and objective: The natural progression of prostate cancer is primarily driven by an index lesion (IL). Studies have shown that different metastases within the same patient arise from a single precursor cell. Therefore, our aim is to assess the effectiveness of transrectal microultrasound (MUS) in comparison to multiparametric magnetic resonance imaging (mpMRI) for detecting the IL in prostate cancer. We used quarter-mount pathological results as the reference standard for this evaluation.
    Materials and methods: Three hundred and sixty-three patients who underwent Robot-Assisted Radical Prostatectomy (RARP) from June 2021 to August 2022 were included. All received mpMRI and MUS before RARP. MUS was performed by experienced operators blinded to mpMRI and biopsy results. The IL in the radical prostatectomy specimen was defined as the lesion with extraprostatic extension, the highest Grade Group (GG), or the largest tumor volume if the GG was the same. The correlation between imaging and final pathology findings was performed. A descriptive statistical analysis is presented.
    Results: The patients' prostates were analyzed in 12 regions (anterior/posterior, right/left, apex/mid/base). A total of 4308 regions were identified. Of these, 935 were involved by the ILs. Compared with final pathology, MUS demonstrated a sensitivity, specificity, PPV, and NPV of 68.7%, 96.3%, 80.8%, and 93.1%, respectively, while mpMRI showed a sensitivity, specificity, PPV, and NPV of 68.6%, 97.2%, 86.1%, and 92.5%, respectively, for the detection of the IL. Most of the lesions missed by MUS were located in the anterior zone (62%).
    Conclusion: MUS exhibits a diagnostic performance similar to mpMRI when it comes to detecting the IL in prostate cancer. MUS is a cost-effective option, offers real-time evaluation, and has no delay in the acquisition process.
    MeSH term(s) Male ; Humans ; Magnetic Resonance Imaging/methods ; Prostatic Neoplasms/diagnostic imaging ; Prostatic Neoplasms/surgery ; Prostate/diagnostic imaging ; Prostate/pathology ; Multiparametric Magnetic Resonance Imaging ; Prostatectomy ; Retrospective Studies
    Language English
    Publishing date 2023-10-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604707-5
    ISSN 1097-0045 ; 0270-4137
    ISSN (online) 1097-0045
    ISSN 0270-4137
    DOI 10.1002/pros.24628
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Towards a Highly Usable, Mobile Electronic Platform for Patient Recruitment and Consent Management.

    Robins, Daniel / Brody, Rachel / Jeong, In Cheol / Parvanova, Irena / Liu, Jiazhen / Finkelstein, Joseph

    Studies in health technology and informatics

    2020  Volume 270, Page(s) 1066–1070

    Abstract: This study seeks to assess usability and acceptance of E-Consent on mobile devices such as tablet computers for collecting universal biobank consents. Usability inspection occurred via cognitive walkthroughs and heuristics evaluations, supplemented by ... ...

    Abstract This study seeks to assess usability and acceptance of E-Consent on mobile devices such as tablet computers for collecting universal biobank consents. Usability inspection occurred via cognitive walkthroughs and heuristics evaluations, supplemented by surveys to capture health literacy, patient engagement, and other metrics. 17 patients of varied ages, backgrounds, and occupations participated in the study. The System Usability Scale (SUS) provided a standardized reference for usability and satisfaction, and the mean result of 84.4 placed this mobile iteration in the top 10th percentile. A semi-structured qualitative interview provided copious actionable feedback, which will inform the next iteration of this project. Overall, this implementation of the E-Consent framework on mobile devices was considered easy-to-use, satisfying, and engaging, allowing users to progress through the consent materials at their own pace. The platform has once again demonstrated high usability and high levels of user acceptance, this time in a novel setting.
    MeSH term(s) Heuristics ; Humans ; Informed Consent ; Mobile Applications ; Patient Selection ; Surveys and Questionnaires
    Language English
    Publishing date 2020-05-29
    Publishing country Netherlands
    Document type Journal Article
    ISSN 1879-8365
    ISSN (online) 1879-8365
    DOI 10.3233/SHTI200325
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Landscape of natural killer cell activity in head and neck squamous cell carcinoma.

    Charap, Andrew J / Enokida, Tomohiro / Brody, Rachel / Sfakianos, John / Miles, Brett / Bhardwaj, Nina / Horowitz, Amir

    Journal for immunotherapy of cancer

    2021  Volume 8, Issue 2

    Abstract: Head and neck squamous cell carcinoma (HNSCC) encompasses a set of cancers arising from the epithelia of the upper aerodigestive tract, accounting for a significant burden of disease worldwide due to the disease's mortality, morbidity, and predilection ... ...

    Abstract Head and neck squamous cell carcinoma (HNSCC) encompasses a set of cancers arising from the epithelia of the upper aerodigestive tract, accounting for a significant burden of disease worldwide due to the disease's mortality, morbidity, and predilection for recurrence. Prognosis of HNSCC in the recurrent and/or metastatic (R/M-HNSCC) setting is especially poor and effective treatment options increasingly rely on modulating T-cell antitumor responses. Still, immunotherapy response rates are generally low, prompting the exploration of novel strategies that incorporate other effector cells within the tumor microenvironment. Within the last decade, important advances have been made leveraging the powerful innate antitumor function of natural killer (NK) cells to treat solid tumors, including head and neck squamous cell carcinoma. NK cells are hybrid innate-adaptive effector cells capable of directly eliminating tumor cells in addition to initiating adaptive antitumor immune responses. In the setting of HNSCC, NK cells are important for tumor surveillance and control, and NK cell infiltration has repeatedly been associated with a favorable prognosis. Yet, HNSCC-infiltrating NK cells are susceptible to an array of immune evasion strategies employed by tumors that must be overcome to fully realize the antitumor potential of NK cells. We believe that a conceptual framework informed by the basic biological understanding of the mechanisms underlying NK cell activation can improve treatment of HNSCC, in part by selecting for patients most likely to respond to NK cell-based immunotherapy. Herein, we review the activity of NK cells in HNSCC, paying special attention to the role of environmental and genetic determinants of NK cell antitumor function. Moreover, we explore the evidence that NK cells are a crucial determinant of the efficacy of both established and emerging treatments for HNSCC.
    Language English
    Publishing date 2021-02-08
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2020-001523
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: An inflammatory proposal for hepatocarcinogenesis.

    Brody, Rachel I / Theise, Neil D

    Hepatology (Baltimore, Md.)

    2012  Volume 56, Issue 1, Page(s) 382–384

    Language English
    Publishing date 2012-07
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.25759
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: HIF1alpha cardioprotection in COVID-19 patients

    Wang, Bingyan Jessica / Vadakke-Madathil, Sangeetha / Croft, Lori B / Brody, Rachel I / Chaudhry, Hina W

    medRxiv

    Abstract: Importance SARS-CoV-2 infection directly causes severe acute respiratory illness, leading to systemic tissue hypoxia and ischemia including the heart. Myocardial cytopathy associated with hypoxic response has been largely overlooked in COVID-19 patients. ...

    Abstract Importance SARS-CoV-2 infection directly causes severe acute respiratory illness, leading to systemic tissue hypoxia and ischemia including the heart. Myocardial cytopathy associated with hypoxic response has been largely overlooked in COVID-19 patients. Additionally, histology analysis and cardiac function of COVID-19 cases are often reported separately, rendering an incomplete understanding of COVID-19 cardiac symptoms. Objective To examine the relationship between myocardial cellular responses to hypoxic stress versus cardiac functional alterations within the same COVID-19 patients. Design, Setting, and Participants Cellular hypoxia Inducible Factor 1 alpha (HIF1α) expression was analyzed by immunohistochemistry using post-mortem COVID-19 heart and lung tissues with known cardiac echocardiography records from a total of 8 patients. Clinical echocardiography data were obtained from Mount Sinai Heart between March to December, 2020. All gender and age groups were considered as long as cardiac involvement meets the preserved (EF > 50%) or moderate to severe (EF < 45%) criteria with confirmed SARS-CoV-2 infection. Cell-type specific subcellular localization of HIF1α expression and nuclear stability was examined by immunohistochemistry and transmission electronic microscopy (TEM). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to quantify apoptosis. Main Outcomes and Measures No planned outcomes of this study as this is a retrospective analysis based on post-mortem specimens exclusively. Results Cardiac HIF1α expression was found to be significantly higher in patients with preserved EF levels than it was in the low EF group. In the preserved EF group, HIF1α is protective against apoptosis predominantly in endothelial cells and cardiac fibroblasts. In the low EF group, HIF1α protects cardiomyocyte nuclear integrity as evident by its nuclear accumulation with nuclear envelope preservation. Conclusions and Relevance This study establishes a direct link of cardiac cellular responses to hypoxic stress with matching functional and histological data, serving as one of the first studies to bridge previous stand-alone clinical data and cellular data. The protective role of HIF1α in hearts may help predict cardiac involvement in not only COVID-19 patients, but also decipher the underlying mechanisms in other forms of viral cardiomyopathy.
    Keywords covid19
    Language English
    Publishing date 2021-08-07
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.08.05.21258160
    Database COVID19

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