{"cells":[{"metadata":{},"cell_type":"markdown","source":"#COVID-19 and the Cytokine Storm: The Crucial Role of IL-6\n\nEmerging data suggest that many patients infected with COVID-19 may die due to an excessive response of their immune system, characterized by the abnormal release of circulating cytokines, termed cytokine release syndrome (CRS). CRS plays a major role in the deterioration of COVID-19 patients, from pneumonia through acute respiratory distress syndrome (ARDS), cumulating in systemic inflammation and ultimately multi-system organ failure. This phenomenon of a plethora of cytokines wreaking havoc throughout the body is often vividly referred to as “cytokine storm.” https://www.enzolifesciences.com/science-center/technotes/2020/april/covid-19-and-the-cytokine-storm-the-crucial-role-of-il-6/","execution_count":null},{"metadata":{"_kg_hide-input":true,"trusted":true},"cell_type":"code","source":"#codes from Rodrigo Lima  @rodrigolima82\nfrom IPython.display import Image\nImage(url = 'https://encrypted-tbn0.gstatic.com/images?q=tbn%3AANd9GcQ5v1AkT5BgOsGR2OHLDZG8gTvrVXLoi-uXM9FpSGlFXnTr3RgG&usqp=CAU',width=400,height=400)","execution_count":null,"outputs":[]},{"metadata":{},"cell_type":"markdown","source":"youtube.com","execution_count":null},{"metadata":{"_uuid":"8f2839f25d086af736a60e9eeb907d3b93b6e0e5","_cell_guid":"b1076dfc-b9ad-4769-8c92-a6c4dae69d19","trusted":true,"_kg_hide-output":true,"collapsed":true},"cell_type":"code","source":"# This Python 3 environment comes with many helpful analytics libraries installed\n# It is defined by the kaggle/python Docker image: https://github.com/kaggle/docker-python\n# For example, here's several helpful packages to load\n\nimport numpy as np # linear algebra\nimport pandas as pd # data processing, CSV file I/O (e.g. pd.read_csv)\nimport seaborn as sns\nimport matplotlib.pyplot as plt\nimport plotly.graph_objs as go\nimport plotly.offline as py\nimport plotly.express as px\nimport json\n\n# Input data files are available in the read-only \"../input/\" directory\n# For example, running this (by clicking run or pressing Shift+Enter) will list all files under the input directory\n\nimport os\nfor dirname, _, filenames in os.walk('/kaggle/input'):\n    for filename in filenames:\n        print(os.path.join(dirname, filename))\n\n# You can write up to 5GB to the current directory (/kaggle/working/) that gets preserved as output when you create a version using \"Save & Run All\" \n# You can also write temporary files to /kaggle/temp/, but they won't be saved outside of the current session","execution_count":null,"outputs":[]},{"metadata":{},"cell_type":"markdown","source":"#\"Cytokine Storm\", IL-6 (The interleukin 6 cytokine ) pro-inflammatory properties, and it functions through two pathways: cis or trans.\n\nMany cytokines take part in the “cytokine storm” in COVID-19 patients, including IL-6, IL-1, IL-2, IL-10, TNF-α and IFN-γ; however, a crucial role seems to be played by IL-6, whose increased levels in the serum have been correlated with respiratory failure, ARDS, and adverse clinical outcomes.\n\nIL-6 has significant pro-inflammatory properties, and it functions through two main signaling pathways: cis or trans. In cis signaling, IL-6 forms a complex with the membrane-bound IL-6 receptor (mIL-6R) and gp130 which then activates downstream the Janus kinases (JAKs) and signal transducer and activator of transcription 3 (STAT3). The activation of this signal cascade leads to pleiotropic effects on the acquired immune system (B and T cells) as well as the innate immune system (neutrophils, macrophages, and natural killer cells) which can contribute to CRS.\n\nIn trans signaling, high circulating IL-6 concentrations bind to the soluble form of IL-6 receptor (sIL-6R) and form a complex with a gp130 dimer on most somatic cell types. This severely aggravates the “cytokine storm” through secretion of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein–1 (MCP-1), IL-8, and additional IL-6, as well as reduced E-cadherin expression on endothelial cells. .https://www.enzolifesciences.com/science-center/technotes/2020/april/covid-19-and-the-cytokine-storm-the-crucial-role-of-il-6/","execution_count":null},{"metadata":{"_uuid":"d629ff2d2480ee46fbb7e2d37f6b5fab8052498a","_cell_guid":"79c7e3d0-c299-4dcb-8224-4455121ee9b0","trusted":true,"_kg_hide-output":true},"cell_type":"code","source":"df = pd.read_csv('/kaggle/input/trec-covid-information-retrieval/CORD-19/CORD-19/metadata.csv')","execution_count":null,"outputs":[]},{"metadata":{},"cell_type":"markdown","source":"#Codes from Salman Chen https://www.kaggle.com/salmanhiro/covids-incubation-transmission-related-articles/comments","execution_count":null},{"metadata":{"trusted":true},"cell_type":"code","source":"title = df.copy()\ntitle = title.dropna(subset=['title'])","execution_count":null,"outputs":[]},{"metadata":{"trusted":true},"cell_type":"code","source":"title['title'] = title['title'].str.replace('[^a-zA-Z]', ' ', regex=True)\ntitle['title'] = title['title'].str.lower()","execution_count":null,"outputs":[]},{"metadata":{},"cell_type":"markdown","source":"#Treating Cytokine Storm\n\nA number of strategies, both old and new, are already being considered or implemented in an attempt to “calm” the “cytokine storm”.\n\nTreatments look to reduce activation of immune cells by interfering with cytokine production or blocking specific signalling pathways dependent on pro-inflammatory cytokines. The pace of the ongoing pandemic has forced researchers and clinicians to rapidly trial various therapies developed earlier for treatment of other conditions (such as Crohn’s disease and arthritis) caused by an overreactive immune system. Immunosuppressive interventions, however, could put COVID-19 patients at greater risk as many of them already suffer from a reduction and functional decline in key immune cells. \n\nAn efficient targeting of the “cytokine storm” requires further research into the complex physiological and cellular responses.https://theconversation.com/coronavirus-cytokine-storm-this-over-active-immune-response-could-be-behind-some-fatal-cases-of-covid-19-136878","execution_count":null},{"metadata":{"trusted":true},"cell_type":"code","source":"title['keyword_cytokine'] = title['title'].str.find('cytokine')","execution_count":null,"outputs":[]},{"metadata":{},"cell_type":"markdown","source":"If the result prompt -1, then the title doesn't contained the keyword.","execution_count":null},{"metadata":{"trusted":true},"cell_type":"code","source":"title.head()","execution_count":null,"outputs":[]},{"metadata":{"trusted":true},"cell_type":"code","source":"included_cytokine = title.loc[title['keyword_cytokine'] != -1]\nincluded_cytokine","execution_count":null,"outputs":[]},{"metadata":{"_kg_hide-output":true,"trusted":true},"cell_type":"code","source":"import json\nfile_path = '/kaggle/input/trec-covid-information-retrieval/CORD-19/CORD-19/document_parses/pdf_json/4fa871503ddbbaaead7a34fce89298a36648f662.json'\nwith open(file_path) as json_file:\n     json_file = json.load(json_file)\njson_file","execution_count":null,"outputs":[]},{"metadata":{},"cell_type":"markdown","source":"Virology Journal Inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with SARS coronavirus\n\nSARS-CoV mainly infects tissues of non-lymphatic origin, and the cytokine profile of those cells can determine the course of disease. Here, we investigated the cytokine response of two human non-lymphatic cell lines, Caco-2 and HEK 293, which are fully permissive for SARS-CoV.\n\nA comparison with established cytokine-inducing viruses revealed that SARS-CoV only weakly triggered a cytokine response. In particular, SARS-CoV did not activate significant transcription of the interferons IFN-α, IFN-β, IFN-λ1, IFN-λ2/3, as well as of the interferoninduced antiviral genes ISG56 and MxA, the chemokine RANTES and the interleukine IL-6. Interestingly, however, SARS-CoV strongly induced the chemokines IP-10 and IL-8 in the colon carcinoma cell line Caco-2, but not in the embryonic kidney cell line 293\n\nAuthor: Martin Spiegel, Friedemann Weber.   Freiburg Universität","execution_count":null},{"metadata":{"_kg_hide-input":false,"trusted":true},"cell_type":"code","source":"storm = pd.read_csv('../input/cusersmarildownloadscytokinecsv/cytokine.csv', sep=';')\nstorm","execution_count":null,"outputs":[]},{"metadata":{"_kg_hide-input":true,"trusted":true},"cell_type":"code","source":"storm.corr()\nplt.figure(figsize=(10,4))\nsns.heatmap(storm.corr(),annot=True,cmap='Greens')\nplt.show()","execution_count":null,"outputs":[]},{"metadata":{"_kg_hide-input":true,"trusted":true},"cell_type":"code","source":"fig = px.parallel_categories(storm, color=\"1447617_at\", color_continuous_scale=px.colors.sequential.Viridis)\nfig.show()","execution_count":null,"outputs":[]},{"metadata":{},"cell_type":"markdown","source":"#Codes from Chris X https://www.kaggle.com/docxian/kawasaki-eda","execution_count":null},{"metadata":{"_kg_hide-input":true,"trusted":true},"cell_type":"code","source":"storm['1447617_at'].hist()\nplt.show()","execution_count":null,"outputs":[]},{"metadata":{"_kg_hide-input":true,"trusted":true},"cell_type":"code","source":"fig = px.scatter_matrix(storm)\nfig.show()","execution_count":null,"outputs":[]},{"metadata":{"_kg_hide-input":true,"trusted":true},"cell_type":"code","source":"# 3D Scatter Plot\nfig = px.scatter_3d(storm, x='1416873_a_at', y='1447617_at', z='Samples')\nfig.show()","execution_count":null,"outputs":[]},{"metadata":{"_kg_hide-input":true,"trusted":true},"cell_type":"code","source":"fig = go.Figure(data=[go.Scatter(\n    x=storm['Samples'][0:10],\n    y=storm['1416873_a_at'][0:10],\n    mode='markers',\n    marker=dict(\n        color=[145, 140, 135, 130, 125, 120,115,110,105,100],\n        size=[100, 90, 70, 60, 60, 60,50,50,40,35],\n        showscale=True\n        )\n)])\nfig.update_layout(\n    title='Cytokine distribution',\n    xaxis_title=\"Samples\",\n    yaxis_title=\"1416873_a_at\",\n)\nfig.show()","execution_count":null,"outputs":[]},{"metadata":{"_kg_hide-input":true,"trusted":true},"cell_type":"code","source":"cnt_srs = df['source_x'].value_counts().head()\ntrace = go.Bar(\n    y=cnt_srs.index[::-1],\n    x=cnt_srs.values[::-1],\n    orientation = 'h',\n    marker=dict(\n        color=cnt_srs.values[::-1],\n        colorscale = 'Blues',\n        reversescale = True\n    ),\n)\n\nlayout = dict(\n    title='Covid-19 & Cytokine Storm',\n    )\ndata = [trace]\nfig = go.Figure(data=data, layout=layout)\npy.iplot(fig, filename=\"source_x\")","execution_count":null,"outputs":[]},{"metadata":{"_kg_hide-input":true,"trusted":true},"cell_type":"code","source":"#codes from Rodrigo Lima  @rodrigolima82\nfrom IPython.display import Image\nImage(url = 'https://encrypted-tbn0.gstatic.com/images?q=tbn%3AANd9GcQrkNf4sgVaJFamrq6wktz4ewSfiNBlXu3fYm2zWSMGzJHu24Bt&usqp=CAU',width=400,height=400)","execution_count":null,"outputs":[]},{"metadata":{},"cell_type":"markdown","source":"emdocs.net","execution_count":null},{"metadata":{},"cell_type":"markdown","source":"Kaggle Notebook Runner: Marília Prata  @mpwolke","execution_count":null}],"metadata":{"kernelspec":{"language":"python","display_name":"Python 3","name":"python3"},"language_info":{"pygments_lexer":"ipython3","nbconvert_exporter":"python","version":"3.6.4","file_extension":".py","codemirror_mode":{"name":"ipython","version":3},"name":"python","mimetype":"text/x-python"}},"nbformat":4,"nbformat_minor":4}