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  1. Article ; Online: Deep learning for quality assessment of optical coherence tomography angiography images

    Rahul M. Dhodapkar / Emily Li / Kristen Nwanyanwu / Ron Adelman / Smita Krishnaswamy / Jay C. Wang

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 9

    Abstract: Abstract Optical coherence tomography angiography (OCTA) is an emerging non-invasive technique for imaging the retinal vasculature. While there are many promising clinical applications for OCTA, determination of image quality remains a challenge. We ... ...

    Abstract Abstract Optical coherence tomography angiography (OCTA) is an emerging non-invasive technique for imaging the retinal vasculature. While there are many promising clinical applications for OCTA, determination of image quality remains a challenge. We developed a deep learning-based system using a ResNet152 neural network classifier, pretrained using ImageNet, to classify images of the superficial capillary plexus in 347 scans from 134 patients. Images were also manually graded by two independent graders as a ground truth for the supervised learning models. Because requirements for image quality may vary depending on the clinical or research setting, two models were trained—one to identify high-quality images and one to identify low-quality images. Our neural network models demonstrated outstanding area under the curve (AUC) metrics for both low quality image identification (AUC = 0.99, 95%CI 0.98–1.00, $$\kappa $$ κ = 0.90) and high quality image identification (AUC = 0.97, 95%CI 0.96–0.99, $$\kappa $$ κ = 0.81), significantly outperforming machine-reported signal strength (AUC = 0.82, 95%CI 0.77–0.86, $$\kappa $$ κ = 0.52 and AUC = 0.78, 95%CI 0.73–0.83, $$\kappa $$ κ = 0.27 respectively). Our study demonstrates that techniques from machine learning may be used to develop flexible and robust methods for quality control of OCTA images.
    Keywords Medicine ; R ; Science ; Q
    Subject code 006
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Neural network predicts need for red blood cell transfusion for patients with acute gastrointestinal bleeding admitted to the intensive care unit

    Dennis Shung / Jessie Huang / Egbert Castro / J. Kenneth Tay / Michael Simonov / Loren Laine / Ramesh Batra / Smita Krishnaswamy

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 12

    Abstract: Abstract Acute gastrointestinal bleeding is the most common gastrointestinal cause for hospitalization. For high-risk patients requiring intensive care unit stay, predicting transfusion needs during the first 24 h using dynamic risk assessment may ... ...

    Abstract Abstract Acute gastrointestinal bleeding is the most common gastrointestinal cause for hospitalization. For high-risk patients requiring intensive care unit stay, predicting transfusion needs during the first 24 h using dynamic risk assessment may improve resuscitation with red blood cell transfusion in admitted patients with severe acute gastrointestinal bleeding. A patient cohort admitted for acute gastrointestinal bleeding (N = 2,524) was identified from the Medical Information Mart for Intensive Care III (MIMIC-III) critical care database and separated into training (N = 2,032) and internal validation (N = 492) sets. The external validation patient cohort was identified from the eICU collaborative database of patients admitted for acute gastrointestinal bleeding presenting to large urban hospitals (N = 1,526). 62 demographic, clinical, and laboratory test features were consolidated into 4-h time intervals over the first 24 h from admission. The outcome measure was the transfusion of red blood cells during each 4-h time interval. A long short-term memory (LSTM) model, a type of Recurrent Neural Network, was compared to a regression-based models on time-updated data. The LSTM model performed better than discrete time regression-based models for both internal validation (AUROC 0.81 vs 0.75 vs 0.75; P < 0.001) and external validation (AUROC 0.65 vs 0.56 vs 0.56; P < 0.001). A LSTM model can be used to predict the need for transfusion of packed red blood cells over the first 24 h from admission to help personalize the care of high-risk patients with acute gastrointestinal bleeding.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: HSV-2 triggers upregulation of MALAT1 in CD4+ T cells and promotes HIV latency reversal

    Carl A. Pierce / Lip Nam Loh / Holly R. Steach / Natalia Cheshenko / Paula Preston-Hurlburt / Fengrui Zhang / Stephanie Stransky / Leah Kravets / Simone Sidoli / William Philbrick / Michel Nassar / Smita Krishnaswamy / Kevan C. Herold / Betsy C. Herold

    The Journal of Clinical Investigation, Vol 133, Iss

    2023  Volume 11

    Abstract: Herpes simplex virus type 2 (HSV-2) coinfection is associated with increased HIV-1 viral loads and expanded tissue reservoirs, but the mechanisms are not well defined. HSV-2 recurrences result in an influx of activated CD4+ T cells to sites of viral ... ...

    Abstract Herpes simplex virus type 2 (HSV-2) coinfection is associated with increased HIV-1 viral loads and expanded tissue reservoirs, but the mechanisms are not well defined. HSV-2 recurrences result in an influx of activated CD4+ T cells to sites of viral replication and an increase in activated CD4+ T cells in peripheral blood. We hypothesized that HSV-2 induces changes in these cells that facilitate HIV-1 reactivation and replication and tested this hypothesis in human CD4+ T cells and 2D10 cells, a model of HIV-1 latency. HSV-2 promoted latency reversal in HSV-2–infected and bystander 2D10 cells. Bulk and single-cell RNA-Seq studies of activated primary human CD4+ T cells identified decreased expression of HIV-1 restriction factors and increased expression of transcripts including MALAT1 that could drive HIV replication in both the HSV-2–infected and bystander cells. Transfection of 2D10 cells with VP16, an HSV-2 protein that regulates transcription, significantly upregulated MALAT1 expression, decreased trimethylation of lysine 27 on histone H3 protein, and triggered HIV latency reversal. Knockout of MALAT1 from 2D10 cells abrogated the response to VP16 and reduced the response to HSV-2 infection. These results demonstrate that HSV-2 contributes to HIV-1 reactivation through diverse mechanisms, including upregulation of MALAT1 to release epigenetic silencing.
    Keywords AIDS/HIV ; Virology ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells

    Valerie A Tornini / Liyun Miao / Ho-Joon Lee / Timothy Gerson / Sarah E Dube / Valeria Schmidt / François Kroll / Yin Tang / Katherine Du / Manik Kuchroo / Charles E Vejnar / Ariel Alejandro Bazzini / Smita Krishnaswamy / Jason Rihel / Antonio J Giraldez

    eLife, Vol

    2023  Volume 12

    Abstract: Thousands of long intergenic non-coding RNAs (lincRNAs) are transcribed throughout the vertebrate genome. A subset of lincRNAs enriched in developing brains have recently been found to contain cryptic open-reading frames and are speculated to encode ... ...

    Abstract Thousands of long intergenic non-coding RNAs (lincRNAs) are transcribed throughout the vertebrate genome. A subset of lincRNAs enriched in developing brains have recently been found to contain cryptic open-reading frames and are speculated to encode micropeptides. However, systematic identification and functional assessment of these transcripts have been hindered by technical challenges caused by their small size. Here, we show that two putative lincRNAs (linc-mipep, also called lnc-rps25, and linc-wrb) encode micropeptides with homology to the vertebrate-specific chromatin architectural protein, Hmgn1, and demonstrate that they are required for development of vertebrate-specific brain cell types. Specifically, we show that NMDA receptor-mediated pathways are dysregulated in zebrafish lacking these micropeptides and that their loss preferentially alters the gene regulatory networks that establish cerebellar cells and oligodendrocytes – evolutionarily newer cell types that develop postnatally in humans. These findings reveal a key missing link in the evolution of vertebrate brain cell development and illustrate a genetic basis for how some neural cell types are more susceptible to chromatin disruptions, with implications for neurodevelopmental disorders and disease.
    Keywords micropeptides ; neurodevelopment ; behavior ; single cell analyses ; cell identity ; gene regulation ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Modeling uniquely human gene regulatory function via targeted humanization of the mouse genome

    Emily V. Dutrow / Deena Emera / Kristina Yim / Severin Uebbing / Acadia A. Kocher / Martina Krenzer / Timothy Nottoli / Daniel B. Burkhardt / Smita Krishnaswamy / Angeliki Louvi / James P. Noonan

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 15

    Abstract: Human Accelerated Regions (HARs) are prime candidates for driving the evolution of uniquely human traits. Using humanized mice, the authors show how one HAR alters gene expression during embryonic development, yielding insight into HAR function. ...

    Abstract Human Accelerated Regions (HARs) are prime candidates for driving the evolution of uniquely human traits. Using humanized mice, the authors show how one HAR alters gene expression during embryonic development, yielding insight into HAR function.
    Keywords Science ; Q
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Learning time-varying information flow from single-cell epithelial to mesenchymal transition data.

    Smita Krishnaswamy / Nevena Zivanovic / Roshan Sharma / Dana Pe'er / Bernd Bodenmiller

    PLoS ONE, Vol 13, Iss 10, p e

    2018  Volume 0203389

    Abstract: Cellular regulatory networks are not static, but continuously reconfigure in response to stimuli via alterations in protein abundance and confirmation. However, typical computational approaches treat them as static interaction networks derived from a ... ...

    Abstract Cellular regulatory networks are not static, but continuously reconfigure in response to stimuli via alterations in protein abundance and confirmation. However, typical computational approaches treat them as static interaction networks derived from a single time point. Here, we provide methods for learning the dynamic modulation of relationships between proteins from static single-cell data. We demonstrate our approach using TGFß induced epithelial-to-mesenchymal transition (EMT) in murine breast cancer cell line, profiled with mass cytometry. We take advantage of the asynchronous rate of transition to EMT in the data and derive a pseudotime EMT trajectory. We propose methods for visualizing and quantifying time-varying edge behavior over the trajectory, and a metric of edge dynamism to predict the effect of drug perturbations on EMT.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Publisher Correction

    Xinyue Chen / Daniel B. Burkhardt / Amaleah A. Hartman / Xiao Hu / Anna E. Eastman / Chao Sun / Xujun Wang / Mei Zhong / Smita Krishnaswamy / Shangqin Guo

    Nature Communications, Vol 11, Iss 1, Pp 1-

    MLL-AF9 initiates transformation from fast-proliferating myeloid progenitors

    2020  Volume 1

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Keywords Science ; Q
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Publisher Correction

    Xinyue Chen / Daniel B. Burkhardt / Amaleah A. Hartman / Xiao Hu / Anna E. Eastman / Chao Sun / Xujun Wang / Mei Zhong / Smita Krishnaswamy / Shangqin Guo

    Nature Communications, Vol 11, Iss 1, Pp 1-

    MLL-AF9 initiates transformation from fast-proliferating myeloid progenitors

    2020  Volume 1

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Keywords Science ; Q
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Immune cells and their inflammatory mediators modify β cells and cause checkpoint inhibitor–induced diabetes

    Ana Luisa Perdigoto / Songyan Deng / Katherine C. Du / Manik Kuchroo / Daniel B. Burkhardt / Alexander Tong / Gary Israel / Marie E. Robert / Stuart P. Weisberg / Nancy Kirkiles-Smith / Angeliki M. Stamatouli / Harriet M. Kluger / Zoe Quandt / Arabella Young / Mei-Ling Yang / Mark J. Mamula / Jordan S. Pober / Mark S. Anderson / Smita Krishnaswamy /
    Kevan C. Herold

    JCI Insight, Vol 7, Iss

    2022  Volume 17

    Abstract: Checkpoint inhibitors (CPIs) targeting programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) have revolutionized cancer treatment but can trigger autoimmune complications, including CPI-induced diabetes ...

    Abstract Checkpoint inhibitors (CPIs) targeting programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) have revolutionized cancer treatment but can trigger autoimmune complications, including CPI-induced diabetes mellitus (CPI-DM), which occurs preferentially with PD-1 blockade. We found evidence of pancreatic inflammation in patients with CPI-DM with shrinkage of pancreases, increased pancreatic enzymes, and in a case from a patient who died with CPI-DM, peri-islet lymphocytic infiltration. In the NOD mouse model, anti–PD-L1 but not anti–CTLA-4 induced diabetes rapidly. RNA sequencing revealed that cytolytic IFN-γ+CD8+ T cells infiltrated islets with anti–PD-L1. Changes in β cells were predominantly driven by IFN-γ and TNF-α and included induction of a potentially novel β cell population with transcriptional changes suggesting dedifferentiation. IFN-γ increased checkpoint ligand expression and activated apoptosis pathways in human β cells in vitro. Treatment with anti–IFN-γ and anti–TNF-α prevented CPI-DM in anti–PD-L1–treated NOD mice. CPIs targeting the PD-1/PD-L1 pathway resulted in transcriptional changes in β cells and immune infiltrates that may lead to the development of diabetes. Inhibition of inflammatory cytokines can prevent CPI-DM, suggesting a strategy for clinical application to prevent this complication.
    Keywords Autoimmunity ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2022-09-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: MLL-AF9 initiates transformation from fast-proliferating myeloid progenitors

    Xinyue Chen / Daniel B. Burkhardt / Amaleah A. Hartman / Xiao Hu / Anna E. Eastman / Chao Sun / Xujun Wang / Mei Zhong / Smita Krishnaswamy / Shangqin Guo

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 15

    Abstract: Not all mutated cells become malignant, suggesting additional requirements for transformation. Here, the authors track blood progenitors from normal to malignancy driven by MLL-AF9, revealing a subset of myeloid progenitors predisposed to transformation ... ...

    Abstract Not all mutated cells become malignant, suggesting additional requirements for transformation. Here, the authors track blood progenitors from normal to malignancy driven by MLL-AF9, revealing a subset of myeloid progenitors predisposed to transformation dependent on their normal cycling state.
    Keywords Science ; Q
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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