Carrel name: keyword-drug-cord
Creating study carrel named keyword-drug-cord
Initializing database
         file: cache/cord-001072-pjv3wy80.json
          key: cord-001072-pjv3wy80
      authors: Hong, Xiaoyun; Wei, Liangming; Wu, Fei; Wu, Zaozhan; Chen, Lizhu; Liu, Zhenguo; Yuan, Weien
        title: Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine
         date: 2013-09-04
      journal: Drug Des Devel Ther
          DOI: 10.2147/dddt.s44401
          sha: 
       doc_id: 1072
     cord_uid: pjv3wy80

         file: cache/cord-006479-iaocovf2.json
          key: cord-006479-iaocovf2
      authors: Schreiber, J.
        title: Medikamenteninduzierte parenchymatöse Lungenerkrankungen
         date: 2009-08-01
      journal: Pneumologe (Berl)
          DOI: 10.1007/s10405-008-0294-9
          sha: 
       doc_id: 6479
     cord_uid: iaocovf2

         file: cache/cord-001244-qdld7hdc.json
          key: cord-001244-qdld7hdc
      authors: Fan, Yue-Nong; Xiao, Xuan; Min, Jian-Liang; Chou, Kuo-Chen
        title: iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking
         date: 2014-03-19
      journal: Int J Mol Sci
          DOI: 10.3390/ijms15034915
          sha: 
       doc_id: 1244
     cord_uid: qdld7hdc

         file: cache/cord-014875-xhzxhwgo.json
          key: cord-014875-xhzxhwgo
      authors: nan
        title: Book Reviews
         date: 2003
      journal: Pharm Res
          DOI: 10.1023/b:pham.0000008097.92834.f4
          sha: 
       doc_id: 14875
     cord_uid: xhzxhwgo

         file: cache/cord-001470-hn288o97.json
          key: cord-001470-hn288o97
      authors: Pivette, Mathilde; Mueller, Judith E; Crépey, Pascal; Bar-Hen, Avner
        title: Drug sales data analysis for outbreak detection of infectious diseases: a systematic literature review
         date: 2014-11-18
      journal: BMC Infect Dis
          DOI: 10.1186/s12879-014-0604-2
          sha: 
       doc_id: 1470
     cord_uid: hn288o97

         file: cache/cord-006226-fn7zlutj.json
          key: cord-006226-fn7zlutj
      authors: nan
        title: Abstracts of the 4th annual meeting of the German Society of Clinical Pharmacology and Therapy: Hannover, 14–17 September 1994
         date: 1994
      journal: Eur J Clin Pharmacol
          DOI: 10.1007/bf00193489
          sha: 
       doc_id: 6226
     cord_uid: fn7zlutj

         file: cache/cord-001151-mdej7nhj.json
          key: cord-001151-mdej7nhj
      authors: Kumar De, Amit; Datta, Sriparna; Mukherjee, Arup
        title: Application of an Amine Functionalized Biopolymer in the Colonic Delivery of Glycyrrhizin: A Design and In Vivo Efficacy Study
         date: 2013-05-18
      journal: Sci Pharm
          DOI: 10.3797/scipharm.1301-14
          sha: 
       doc_id: 1151
     cord_uid: mdej7nhj

         file: cache/cord-016309-6mw8okmt.json
          key: cord-016309-6mw8okmt
      authors: Bule, Mohammed; Khan, Fazlullah; Niaz, Kamal
        title: Antivirals: Past, Present and Future
         date: 2019-06-06
      journal: Recent Advances in Animal Virology
          DOI: 10.1007/978-981-13-9073-9_22
          sha: 
       doc_id: 16309
     cord_uid: 6mw8okmt

         file: cache/cord-003118-58ta20fg.json
          key: cord-003118-58ta20fg
      authors: Van Norman, Gail A.
        title: Expanding Patient Access to Investigational New Drugs: Overview of Intermediate and Widespread Treatment Investigational New Drugs, and Emergency Authorization in Public Health Emergencies
         date: 2018-06-25
      journal: JACC Basic Transl Sci
          DOI: 10.1016/j.jacbts.2018.02.001
          sha: 
       doc_id: 3118
     cord_uid: 58ta20fg

         file: cache/cord-015684-q10sx1dm.json
          key: cord-015684-q10sx1dm
      authors: Cacabelos, Ramón
        title: Pharmacogenomic Biomarkers in Neuropsychiatry: The Path to Personalized Medicine in Mental Disorders
         date: 2009
      journal: The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes
          DOI: 10.1007/978-90-481-2298-1_1
          sha: 
       doc_id: 15684
     cord_uid: q10sx1dm

         file: cache/cord-000204-hd12p867.json
          key: cord-000204-hd12p867
      authors: Wu, Han-Chung; Chang, De-Kuan
        title: Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy
         date: 2010-05-05
      journal: J Oncol
          DOI: 10.1155/2010/723798
          sha: 
       doc_id: 204
     cord_uid: hd12p867

         file: cache/cord-009763-44fexcpt.json
          key: cord-009763-44fexcpt
      authors: Reddy, Mynampati Akshitha; Pradhan, Bikash Kumar; Qureshi, Dilshad; Pal, Sumit Kumar; Pal, Kunal
        title: Internet-of-Things-Enabled Dual-Channel Iontophoretic Drug Delivery System for Elderly Patient Medication Management
         date: 2020-03-01
      journal: J Med Device
          DOI: 10.1115/1.4045933
          sha: 
       doc_id: 9763
     cord_uid: 44fexcpt

         file: cache/cord-007798-9ht7cqhu.json
          key: cord-007798-9ht7cqhu
      authors: Smith, Silas W.
        title: Drugs and pharmaceuticals: management of intoxication and antidotes
         date: 2010-02-25
      journal: Molecular, Clinical and Environmental Toxicology
          DOI: 10.1007/978-3-7643-8338-1_12
          sha: 
       doc_id: 7798
     cord_uid: 9ht7cqhu

         file: cache/cord-000182-ni6iyzdn.json
          key: cord-000182-ni6iyzdn
      authors: He, Zhisong; Zhang, Jian; Shi, Xiao-He; Hu, Le-Le; Kong, Xiangyin; Cai, Yu-Dong; Chou, Kuo-Chen
        title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features
         date: 2010-03-11
      journal: PLoS One
          DOI: 10.1371/journal.pone.0009603
          sha: 
       doc_id: 182
     cord_uid: ni6iyzdn

         file: cache/cord-018595-x3tleomb.json
          key: cord-018595-x3tleomb
      authors: Dodiuk-Gad, Roni P.; Chung, Wen-Hung; Shear, Neil H.
        title: Adverse Medication Reactions
         date: 2017-04-25
      journal: Clinical and Basic Immunodermatology
          DOI: 10.1007/978-3-319-29785-9_25
          sha: 
       doc_id: 18595
     cord_uid: x3tleomb

         file: cache/cord-007511-5d5authn.json
          key: cord-007511-5d5authn
      authors: Gil, JP; Gil Berglund, E
        title: CYP2C8 and antimalaria drug efficacy
         date: 2007-02-07
      journal: Pharmacogenomics
          DOI: 10.2217/14622416.8.2.187
          sha: 
       doc_id: 7511
     cord_uid: 5d5authn

         file: cache/cord-016283-b6yywn9f.json
          key: cord-016283-b6yywn9f
      authors: Hasan, Ashfaq; Praveen, Sai Haranath; Tarke, Chandrakant; Abdullah, Fahad
        title: Clinical Aspects and Principles of Management of Tuberculosis
         date: 2019-08-07
      journal: Mycobacterium Tuberculosis: Molecular Infection Biology, Pathogenesis, Diagnostics and New Interventions
          DOI: 10.1007/978-981-32-9413-4_20
          sha: 
       doc_id: 16283
     cord_uid: b6yywn9f

         file: cache/cord-017583-72mbsib7.json
          key: cord-017583-72mbsib7
      authors: Devarajan, Padma V.; Dawre, Shilpa M.; Dutta, Rinku
        title: Infectious Diseases: Need for Targeted Drug Delivery
         date: 2014-09-01
      journal: Targeted Drug Delivery : Concepts and Design
          DOI: 10.1007/978-3-319-11355-5_3
          sha: 
       doc_id: 17583
     cord_uid: 72mbsib7

         file: cache/cord-024833-e6vcf4un.json
          key: cord-024833-e6vcf4un
      authors: nan
        title: Forum
         date: 2019-12-19
      journal: Pharmaceut Med
          DOI: 10.1007/s40290-019-00321-z
          sha: 
       doc_id: 24833
     cord_uid: e6vcf4un

         file: cache/cord-016460-39yniw0t.json
          key: cord-016460-39yniw0t
      authors: Ben-Chetrit, Eldad
        title: Colchicine
         date: 2018-07-31
      journal: Textbook of Autoinflammation
          DOI: 10.1007/978-3-319-98605-0_40
          sha: 
       doc_id: 16460
     cord_uid: 39yniw0t

         file: cache/cord-002774-tpqsjjet.json
          key: cord-002774-tpqsjjet
      authors: nan
        title: Section II: Poster Sessions
         date: 2017-12-01
      journal: J Urban Health
          DOI: 10.1093/jurban/jti137
          sha: 
       doc_id: 2774
     cord_uid: tpqsjjet

         file: cache/cord-033723-jy5fdsp9.json
          key: cord-033723-jy5fdsp9
      authors: Orhobor, Oghenejokpeme I.; French, Joseph; Soldatova, Larisa N.; King, Ross D.
        title: Generating Explainable and Effective Data Descriptors Using Relational Learning: Application to Cancer Biology
         date: 2020-09-19
      journal: Discovery Science
          DOI: 10.1007/978-3-030-61527-7_25
          sha: 
       doc_id: 33723
     cord_uid: jy5fdsp9

         file: cache/cord-015334-8p124rwp.json
          key: cord-015334-8p124rwp
      authors: nan
        title: ESCP 36th European Symposium on Clinical Pharmacy ‘Implementing Clinical Pharmacy in Community and Hospital Settings: Sharing the Experience’, Istanbul, Turkey 25–27 October 2007; Abstracts
         date: 2008-06-11
      journal: Pharm World Sci
          DOI: 10.1007/s11096-008-9226-3
          sha: 
       doc_id: 15334
     cord_uid: 8p124rwp

         file: cache/cord-017062-dkw2sugl.json
          key: cord-017062-dkw2sugl
      authors: Singh, Indu; Swami, Rajan; Khan, Wahid; Sistla, Ramakrishna
        title: Delivery Systems for Lymphatic Targeting
         date: 2013-10-08
      journal: Focal Controlled Drug Delivery
          DOI: 10.1007/978-1-4614-9434-8_20
          sha: 
       doc_id: 17062
     cord_uid: dkw2sugl

         file: cache/cord-104431-3rblzyry.json
          key: cord-104431-3rblzyry
      authors: Hill, Andrew; Wang, Junzheng; Levi, Jacob; Heath, Katie; Fortunak, Joseph
        title: Minimum costs to manufacture new treatments for COVID-19
         date: 2020-04-30
      journal: nan
          DOI: nan
          sha: 
       doc_id: 104431
     cord_uid: 3rblzyry

         file: cache/cord-257344-d13at1y5.json
          key: cord-257344-d13at1y5
      authors: Ghasemiyeh, Parisa; Mohammadi-Samani, Soliman
        title: COVID-19 Outbreak: Challenges in Pharmacotherapy Based on Pharmacokinetic and Pharmacodynamic Aspects of Drug Therapy in Patients with Moderate to Severe Infection
         date: 2020-09-18
      journal: Heart Lung
          DOI: 10.1016/j.hrtlng.2020.08.025
          sha: 
       doc_id: 257344
     cord_uid: d13at1y5

         file: cache/cord-103876-2rg2qtdq.json
          key: cord-103876-2rg2qtdq
      authors: Watkins, Laura C.; DeGrado, William F.; Voth, Gregory A.
        title: Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics
         date: 2020-06-20
      journal: bioRxiv
          DOI: 10.1101/2020.06.19.162248
          sha: 
       doc_id: 103876
     cord_uid: 2rg2qtdq

         file: cache/cord-020766-0gacqii4.json
          key: cord-020766-0gacqii4
      authors: Murthy, Sreekant; Papazoglou, Elisabeth; Kanagarajan, Nandhakumar; Murthy, Narasim S.
        title: Nanotechnology: Towards the detection and treatment of inflammatory diseases
         date: 2006
      journal: In Vivo Models of Inflammation
          DOI: 10.1007/978-3-7643-7520-1_8
          sha: 
       doc_id: 20766
     cord_uid: 0gacqii4

         file: cache/cord-018714-i291z2ju.json
          key: cord-018714-i291z2ju
      authors: Criado, Paulo Ricardo
        title: Adverse Drug Reactions
         date: 2016-12-31
      journal: Dermatology in Public Health Environments
          DOI: 10.1007/978-3-319-33919-1_26
          sha: 
       doc_id: 18714
     cord_uid: i291z2ju

         file: cache/cord-034406-i1hbx3pz.json
          key: cord-034406-i1hbx3pz
      authors: Matthews, Abigail A.; Ee, Pui Lai Rachel; Ge, Ruowen
        title: Developing inhaled protein therapeutics for lung diseases
         date: 2020-10-30
      journal: Mol Biomed
          DOI: 10.1186/s43556-020-00014-z
          sha: 
       doc_id: 34406
     cord_uid: i1hbx3pz

         file: cache/cord-257318-jejgkcql.json
          key: cord-257318-jejgkcql
      authors: Jain, K.K.
        title: Synthetic Biology and Personalized Medicine
         date: 2012-08-16
      journal: Med Princ Pract
          DOI: 10.1159/000341794
          sha: 
       doc_id: 257318
     cord_uid: jejgkcql

         file: cache/cord-017702-v46ye328.json
          key: cord-017702-v46ye328
      authors: Ganguly, Nirmal Kumar; Saha, Gautam Kumar
        title: Pharmacogenomics and Personalized Medicine for Infectious Diseases
         date: 2013-06-11
      journal: Omics for Personalized Medicine
          DOI: 10.1007/978-81-322-1184-6_27
          sha: 
       doc_id: 17702
     cord_uid: v46ye328

         file: cache/cord-203232-1nnqx1g9.json
          key: cord-203232-1nnqx1g9
      authors: Canturk, Semih; Singh, Aman; St-Amant, Patrick; Behrmann, Jason
        title: Machine-Learning Driven Drug Repurposing for COVID-19
         date: 2020-06-25
      journal: nan
          DOI: nan
          sha: 
       doc_id: 203232
     cord_uid: 1nnqx1g9

         file: cache/cord-252166-qah877pk.json
          key: cord-252166-qah877pk
      authors: Ekins, S; Mestres, J; Testa, B
        title: In silico pharmacology for drug discovery: applications to targets and beyond
         date: 2007-09-01
      journal: British Journal of Pharmacology
          DOI: 10.1038/sj.bjp.0707306
          sha: 
       doc_id: 252166
     cord_uid: qah877pk

         file: cache/cord-004501-guiy89x8.json
          key: cord-004501-guiy89x8
      authors: Cojocaru, Florina-Daniela; Botezat, Doru; Gardikiotis, Ioannis; Uritu, Cristina-Mariana; Dodi, Gianina; Trandafir, Laura; Rezus, Ciprian; Rezus, Elena; Tamba, Bogdan-Ionel; Mihai, Cosmin-Teodor
        title: Nanomaterials Designed for Antiviral Drug Delivery Transport across Biological Barriers
         date: 2020-02-18
      journal: Pharmaceutics
          DOI: 10.3390/pharmaceutics12020171
          sha: 
       doc_id: 4501
     cord_uid: guiy89x8

         file: cache/cord-035236-7rfc73qb.json
          key: cord-035236-7rfc73qb
      authors: Karabasz, Alicja; Bzowska, Monika; Szczepanowicz, Krzysztof
        title: Biomedical Applications of Multifunctional Polymeric Nanocarriers: A Review of Current Literature
         date: 2020-11-06
      journal: Int J Nanomedicine
          DOI: 10.2147/ijn.s231477
          sha: 
       doc_id: 35236
     cord_uid: 7rfc73qb

         file: cache/cord-102823-zult69f2.json
          key: cord-102823-zult69f2
      authors: Nguyen, Thin; Le, Hang; Quinn, Thomas P.; Nguyen, Tri; Le, Thuc Duy; Venkatesh, Svetha
        title: GraphDTA: Predicting drug–target binding affinity with graph neural networks
         date: 2020-10-02
      journal: bioRxiv
          DOI: 10.1101/684662
          sha: 
       doc_id: 102823
     cord_uid: zult69f2

         file: cache/cord-104493-yqf7tyo4.json
          key: cord-104493-yqf7tyo4
      authors: Keshmiri Neghab, Hoda; Azadeh, Seyedeh Sara; Soheilifar, Mohammad Hasan; Dashtestani, Fariba
        title: Nanoformulation-Based Antiviral Combination Therapy for Treatment of COVID-19
         date: 2020
      journal: Avicenna J Med Biotechnol
          DOI: nan
          sha: 
       doc_id: 104493
     cord_uid: yqf7tyo4

         file: cache/cord-258128-qtmjgrml.json
          key: cord-258128-qtmjgrml
      authors: Mirjalili, Mahtabalsadat; Shafiekhani, Mojtaba; Vazin, Afsaneh
        title: Coronavirus Disease 2019 (COVID-19) and Transplantation: Pharmacotherapeutic Management of Immunosuppression Regimen
         date: 2020-07-03
      journal: Ther Clin Risk Manag
          DOI: 10.2147/tcrm.s256246
          sha: 
       doc_id: 258128
     cord_uid: qtmjgrml

         file: cache/cord-232446-vvb2ffhv.json
          key: cord-232446-vvb2ffhv
      authors: Mongia, Aanchal; Saha, Sanjay Kr.; Chouzenoux, Emilie; Majumdar, Angshul
        title: A computational approach to aid clinicians in selecting anti-viral drugs for COVID-19 trials
         date: 2020-07-03
      journal: nan
          DOI: nan
          sha: 
       doc_id: 232446
     cord_uid: vvb2ffhv

         file: cache/cord-256852-lrz17bdx.json
          key: cord-256852-lrz17bdx
      authors: Nayyar, Gaurvika M. L.; Attaran, Amir; Clark, John P.; Culzoni, M. Julia; Fernandez, Facundo M.; Herrington, James E.; Kendall, Megan; Newton, Paul N.; Breman, Joel G.
        title: Responding to the Pandemic of Falsified Medicines
         date: 2015-06-03
      journal: Am J Trop Med Hyg
          DOI: 10.4269/ajtmh.14-0393
          sha: 
       doc_id: 256852
     cord_uid: lrz17bdx

         file: cache/cord-023509-tvqpv6fp.json
          key: cord-023509-tvqpv6fp
      authors: Corrin, Bryan; Nicholson, Andrew G.
        title: Occupational, environmental and iatrogenic lung disease
         date: 2011-03-02
      journal: Pathology of the Lungs
          DOI: 10.1016/b978-0-7020-3369-8.00007-0
          sha: 
       doc_id: 23509
     cord_uid: tvqpv6fp

         file: cache/cord-022082-1dq623oe.json
          key: cord-022082-1dq623oe
      authors: Greaves, Peter
        title: Respiratory Tract
         date: 2007-09-28
      journal: Histopathology of Preclinical Toxicity Studies
          DOI: 10.1016/b978-044452771-4/50007-9
          sha: 
       doc_id: 22082
     cord_uid: 1dq623oe

         file: cache/cord-261311-j6bmgmhz.json
          key: cord-261311-j6bmgmhz
      authors: Parreiras Martins, Maria Auxiliadora; Fonseca de Medeiros, Amanda; Dias Carneiro de Almeida, Claudmeire; Moreira Reis, Adriano Max
        title: Preparedness of pharmacists to respond to the emergency of the COVID-19 pandemic in Brazil: a comprehensive overview
         date: 2020-07-31
      journal: Drugs Ther Perspect
          DOI: 10.1007/s40267-020-00761-7
          sha: 
       doc_id: 261311
     cord_uid: j6bmgmhz

         file: cache/cord-199630-2lmwnfda.json
          key: cord-199630-2lmwnfda
      authors: Ray, Sumanta; Lall, Snehalika; Mukhopadhyay, Anirban; Bandyopadhyay, Sanghamitra; Schonhuth, Alexander
        title: Predicting potential drug targets and repurposable drugs for COVID-19 via a deep generative model for graphs
         date: 2020-07-05
      journal: nan
          DOI: nan
          sha: 
       doc_id: 199630
     cord_uid: 2lmwnfda

         file: cache/cord-265848-afkeuwup.json
          key: cord-265848-afkeuwup
      authors: nan
        title: Chapter 2 Emergency Management of Poisoning
         date: 2007-12-31
      journal: Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose
          DOI: 10.1016/b978-0-7216-0693-4.50007-4
          sha: 
       doc_id: 265848
     cord_uid: afkeuwup

         file: cache/cord-253115-ekgdsv4f.json
          key: cord-253115-ekgdsv4f
      authors: Mehta, Meenu; Deeksha,; Tewari, Devesh; Gupta, Gaurav; Awasthi, Rajendra; Singh, Harjeet; Pandey, Parijat; Chellappan, Dinesh Kumar; Wadhwa, Ridhima; Collet, Trudi; Hansbro, Philip M.; Kumar, S Rajesh; Thangavelu, Lakshmi; Negi, Poonam; Dua, Kamal; Satija, Saurabh
        title: Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases
         date: 2019-08-01
      journal: Chemico-Biological Interactions
          DOI: 10.1016/j.cbi.2019.05.028
          sha: 
       doc_id: 253115
     cord_uid: ekgdsv4f

         file: cache/cord-214795-8jweuq50.json
          key: cord-214795-8jweuq50
      authors: Mongia, Aanchal; Jain, Stuti; Chouzenoux, Emilie; Majumda, Angshul
        title: DeepVir -- Graphical Deep Matrix Factorization for"In Silico"Antiviral Repositioning: Application to COVID-19
         date: 2020-09-22
      journal: nan
          DOI: nan
          sha: 
       doc_id: 214795
     cord_uid: 8jweuq50

         file: cache/cord-130351-w9mij6c6.json
          key: cord-130351-w9mij6c6
      authors: Mamidala, Estari; Davella, Rakesh; Gurrapu, Swapna; Shivakrishna, Pujala
        title: In silico identification of clinically approved medicines against the main protease of SARS-CoV-2, causative agent of covid-19
         date: 2020-04-25
      journal: nan
          DOI: nan
          sha: 
       doc_id: 130351
     cord_uid: w9mij6c6

         file: cache/cord-257144-3q0un5rl.json
          key: cord-257144-3q0un5rl
      authors: Giri, Allan; Das, Ankita; Sarkar, Ajoy K.; Giri, Ashok K.
        title: Mutagenic, Genotoxic and Immunomodulatory effects of Hydroxychloroquine and Chloroquine: a review to evaluate its potential to use as a prophylactic drug against COVID-19
         date: 2020-09-02
      journal: Genes Environ
          DOI: 10.1186/s41021-020-00164-0
          sha: 
       doc_id: 257144
     cord_uid: 3q0un5rl

         file: cache/cord-263803-0n41gylj.json
          key: cord-263803-0n41gylj
      authors: Villoutreix, Bruno O.; Beaune, Philippe H.; Tamouza, Ryad; Krishnamoorthy, Rajogapal; Leboyer, Marion
        title: Prevention of COVID-19 by drug repurposing: rationale from drugs prescribed for mental disorders
         date: 2020-06-25
      journal: Drug Discov Today
          DOI: 10.1016/j.drudis.2020.06.022
          sha: 
       doc_id: 263803
     cord_uid: 0n41gylj

         file: cache/cord-261170-arnwk287.json
          key: cord-261170-arnwk287
      authors: Gallimore, W.
        title: Chapter 18 Marine Metabolites Oceans of Opportunity
         date: 2017-12-31
      journal: Pharmacognosy
          DOI: 10.1016/b978-0-12-802104-0.00018-4
          sha: 
       doc_id: 261170
     cord_uid: arnwk287

         file: cache/cord-178783-894gkrsk.json
          key: cord-178783-894gkrsk
      authors: Zhang, Rui; Hristovski, Dimitar; Schutte, Dalton; Kastrin, Andrej; Fiszman, Marcelo; Kilicoglu, Halil
        title: Drug Repurposing for COVID-19 via Knowledge Graph Completion
         date: 2020-10-19
      journal: nan
          DOI: nan
          sha: 
       doc_id: 178783
     cord_uid: 894gkrsk

         file: cache/cord-252147-bvtchcbt.json
          key: cord-252147-bvtchcbt
      authors: Domingo-Espín, Joan; Unzueta, Ugutz; Saccardo, Paolo; Rodríguez-Carmona, Escarlata; Corchero, José Luís; Vázquez, Esther; Ferrer-Miralles, Neus
        title: Engineered Biological Entities for Drug Delivery and Gene Therapy: Protein Nanoparticles
         date: 2011-11-15
      journal: Prog Mol Biol Transl Sci
          DOI: 10.1016/b978-0-12-416020-0.00006-1
          sha: 
       doc_id: 252147
     cord_uid: bvtchcbt

         file: cache/cord-256118-gxhhwqdd.json
          key: cord-256118-gxhhwqdd
      authors: Abadie, R.; Dombrowski, K.
        title: “Caballo”: risk environments, drug sharing and the emergence of a hepatitis C virus epidemic among people who inject drugs in Puerto Rico
         date: 2020-10-23
      journal: Harm Reduct J
          DOI: 10.1186/s12954-020-00421-z
          sha: 
       doc_id: 256118
     cord_uid: gxhhwqdd

         file: cache/cord-258614-7unadw41.json
          key: cord-258614-7unadw41
      authors: Ogidigo, Joyce Oloaigbe; Iwuchukwu, Emmanuel A.; Ibeji, Collins U.; Okpalefe, Okiemute; Soliman, Mahmoud E. S.
        title: Natural phyto, compounds as possible noncovalent inhibitors against SARS-CoV2 protease: computational approach
         date: 2020-10-25
      journal: Journal of biomolecular structure & dynamics
          DOI: 10.1080/07391102.2020.1837681
          sha: 
       doc_id: 258614
     cord_uid: 7unadw41

         file: cache/cord-267979-k70gnrdw.json
          key: cord-267979-k70gnrdw
      authors: Yıldız-Peköz, Ayca; Ehrhardt, Carsten
        title: Advances in Pulmonary Drug Delivery
         date: 2020-09-23
      journal: Pharmaceutics
          DOI: 10.3390/pharmaceutics12100911
          sha: 
       doc_id: 267979
     cord_uid: k70gnrdw

         file: cache/cord-255895-6at9gelt.json
          key: cord-255895-6at9gelt
      authors: Han, Namshik; Hwang, Woochang; Tzelepis, Konstantinos; Schmerer, Patrick; Yankova, Eliza; MacMahon, Méabh; Lei, Winnie; Katritsis, Nicholas M; Liu, Anika; Schuldt, Alison; Harris, Rebecca; Chapman, Kathryn; McCaughan, Frank; Weber, Friedemann; Kouzarides, Tony
        title: Identification of SARS-CoV-2 induced pathways reveal drug repurposing strategies
         date: 2020-08-25
      journal: bioRxiv
          DOI: 10.1101/2020.08.24.265496
          sha: 
       doc_id: 255895
     cord_uid: 6at9gelt

         file: cache/cord-267608-0odu8lus.json
          key: cord-267608-0odu8lus
      authors: Chen, Daohong; Qi, Eric Yining
        title: Innovative highlights of clinical drug trial design
         date: 2020-06-03
      journal: Transl Res
          DOI: 10.1016/j.trsl.2020.05.007
          sha: 
       doc_id: 267608
     cord_uid: 0odu8lus

         file: cache/cord-203191-7ftg6bfx.json
          key: cord-203191-7ftg6bfx
      authors: Guo, Kai; Wang, Zhihan; Gao, Pan; Pu, Qinqin; Wu, Min; Huang, Canhua; Hur, Junguk
        title: Identification of Repurposal Drugs and Adverse Drug Reactions for Various Courses of Coronavirus Disease 2019 (COVID-19) Based on Single-cell RNA Sequencing Data
         date: 2020-05-16
      journal: nan
          DOI: nan
          sha: 
       doc_id: 203191
     cord_uid: 7ftg6bfx

         file: cache/cord-255460-r5p5helx.json
          key: cord-255460-r5p5helx
      authors: Aggarwal, Sadhna; Verma, Sumit Singh; Aggarwal, Sumit; Gupta, Subash Chandra
        title: Drug repurposing for breast cancer therapy: Old weapon for new battle
         date: 2019-09-21
      journal: Semin Cancer Biol
          DOI: 10.1016/j.semcancer.2019.09.012
          sha: 
       doc_id: 255460
     cord_uid: r5p5helx

         file: cache/cord-260215-gsnjlhjd.json
          key: cord-260215-gsnjlhjd
      authors: Dhanani, Jayesh; Fraser, John F.; Chan, Hak-Kim; Rello, Jordi; Cohen, Jeremy; Roberts, Jason A.
        title: Fundamentals of aerosol therapy in critical care
         date: 2016-10-07
      journal: Crit Care
          DOI: 10.1186/s13054-016-1448-5
          sha: 
       doc_id: 260215
     cord_uid: gsnjlhjd

         file: cache/cord-283287-073r80s7.json
          key: cord-283287-073r80s7
      authors: Farhoudian, Ali; Baldacchino, Alexander; Clark, Nicolas; Gerra, Gilberto; Ekhtiari, Hamed; Dom, Geert; Mokri, Azarakhsh; Sadeghi, Mandana; Nematollahi, Pardis; Demasi, Maryanne; Schütz, Christian G.; Hash-emian, Seyed Mohammadreza; Tabarsi, Payam; Galea-Singer, Susanna; Carrà, Giuseppe; Clausen, Thomas; Kouimtsidis, Christos; Tolomeo, Serenella; Radfar, Seyed Ramin; Razaghi, Emran Mohammad
        title: COVID-19 and Substance Use Disorders: Recommendations to a Comprehensive Healthcare Response. An International Society of Addiction Medicine Practice and Policy Interest Group Position Paper
         date: 2020-04-12
      journal: Basic Clin Neurosci
          DOI: 10.32598/bcn.11.covid19.1
          sha: 
       doc_id: 283287
     cord_uid: 073r80s7

         file: cache/cord-263840-1t4ykc01.json
          key: cord-263840-1t4ykc01
      authors: Altay, Ozlem; Mohammadi, Elyas; Lam, Simon; Turkez, Hasan; Boren, Jan; Nielsen, Jens; Uhlen, Mathias; Mardinoglu, Adil
        title: Current status of COVID-19 therapies and drug repositioning applications
         date: 2020-06-20
      journal: iScience
          DOI: 10.1016/j.isci.2020.101303
          sha: 
       doc_id: 263840
     cord_uid: 1t4ykc01

         file: cache/cord-274307-kl0uvrbw.json
          key: cord-274307-kl0uvrbw
      authors: Bordet, Régis
        title: Is the drug a scientific, social or political object?
         date: 2020-05-23
      journal: Therapie
          DOI: 10.1016/j.therap.2020.05.012
          sha: 
       doc_id: 274307
     cord_uid: kl0uvrbw

         file: cache/cord-266294-ua22udlc.json
          key: cord-266294-ua22udlc
      authors: Koch, Oliver; Sheehy, Susanne; Sargent, Catherine; Democratis, Jane; Abbas, Sarah; Schiefermueller, Jurgen; Angus, Brian J.
        title: 29 Antiviral drugs
         date: 2010-12-31
      journal: Side Effects of Drugs Annual
          DOI: 10.1016/s0378-6080(10)32029-0
          sha: 
       doc_id: 266294
     cord_uid: ua22udlc

         file: cache/cord-262442-kjgpriow.json
          key: cord-262442-kjgpriow
      authors: Scalia, Santo; Haghi, Mehra; Losi, Vanessa; Trotta, Valentina; Young, Paul M.; Traini, Daniela
        title: Quercetin solid lipid microparticles: A flavonoid for inhalation lung delivery
         date: 2013-05-13
      journal: Eur J Pharm Sci
          DOI: 10.1016/j.ejps.2013.03.009
          sha: 
       doc_id: 262442
     cord_uid: kjgpriow

         file: cache/cord-268283-eja8fkwv.json
          key: cord-268283-eja8fkwv
      authors: Iftikhar, Hafsa; Ali, Hafiza Nayyer; Farooq, Sadia; Naveed, Hammad; Shahzad-ul-Hussan, Syed
        title: Identification of potential inhibitors of three key enzymes of SARS-CoV2 using computational approach
         date: 2020-06-09
      journal: Comput Biol Med
          DOI: 10.1016/j.compbiomed.2020.103848
          sha: 
       doc_id: 268283
     cord_uid: eja8fkwv

         file: cache/cord-270516-9ol1209i.json
          key: cord-270516-9ol1209i
      authors: Singh, Bhupinder; Lohan, Shikha; Sandhu, Premjeet S.; Jain, Atul; Mehta, Surinder Kumar
        title: Functionalized carbon nanotubes and their promising applications in therapeutics and diagnostics
         date: 2016-04-15
      journal: Nanobiomaterials in Medical Imaging
          DOI: 10.1016/b978-0-323-41736-5.00015-7
          sha: 
       doc_id: 270516
     cord_uid: 9ol1209i

         file: cache/cord-264867-ezsy76mx.json
          key: cord-264867-ezsy76mx
      authors: Rahman, Hamidur; Hossain, Md. Rakib; Ferdous, Tahmina
        title: The recent advancement of low-dimensional nanostructured materials for drug delivery and drug sensing application: A brief review
         date: 2020-09-30
      journal: J Mol Liq
          DOI: 10.1016/j.molliq.2020.114427
          sha: 
       doc_id: 264867
     cord_uid: ezsy76mx

         file: cache/cord-264779-71s7e18i.json
          key: cord-264779-71s7e18i
      authors: Neumann, Natalie R.; Chai, Peter R.; Wood, David M.; Greller, Howard A.; Mycyk, Mark B.
        title: Medical Toxicology and COVID-19: Our Role in a Pandemic
         date: 2020-04-30
      journal: J Med Toxicol
          DOI: 10.1007/s13181-020-00778-4
          sha: 
       doc_id: 264779
     cord_uid: 71s7e18i

         file: cache/cord-273656-xo82zyi6.json
          key: cord-273656-xo82zyi6
      authors: Burry, Lisa D.; Barletta, Jeffrey F.; B.Pharm, David Williamson; Kanji, Salmaan; Maves, Ryan C.; Dichter, Jeffrey; Christian, Michael D.; Geiling, James; Erstad, Brian L.
        title: It Takes a Village… Contending with Drug Shortages During Disasters
         date: 2020-08-14
      journal: Chest
          DOI: 10.1016/j.chest.2020.08.015
          sha: 
       doc_id: 273656
     cord_uid: xo82zyi6

         file: cache/cord-032561-x3qbqy69.json
          key: cord-032561-x3qbqy69
      authors: Liu, Gengqi; Lovell, Jonathan F.; Zhang, Lei; Zhang, Yumiao
        title: Stimulus-Responsive Nanomedicines for Disease Diagnosis and Treatment
         date: 2020-09-02
      journal: Int J Mol Sci
          DOI: 10.3390/ijms21176380
          sha: 
       doc_id: 32561
     cord_uid: x3qbqy69

         file: cache/cord-263312-x7f0hn7f.json
          key: cord-263312-x7f0hn7f
      authors: Tzelepis, Ilias; Kapsetaki, Stefania-Elisavet; Panayidou, Stavria; Apidianakis, Yiorgos
        title: Drosophila melanogaster: a first step and a stepping-stone to anti-infectives
         date: 2013-08-28
      journal: Curr Opin Pharmacol
          DOI: 10.1016/j.coph.2013.08.003
          sha: 
       doc_id: 263312
     cord_uid: x7f0hn7f

         file: cache/cord-263874-q0egnzwf.json
          key: cord-263874-q0egnzwf
      authors: Khan, Md. Arif; Mahmud, Shafi; Alam, A. S. M. Rubayet Ul; Rahman, Md. Ekhtiar; Ahmed, Firoz; Rahmatullah, Mohammed
        title: Comparative molecular investigation of the potential inhibitors against SARS-CoV-2 main protease: a molecular docking study
         date: 2020-07-22
      journal: Journal of biomolecular structure & dynamics
          DOI: 10.1080/07391102.2020.1796813
          sha: 
       doc_id: 263874
     cord_uid: q0egnzwf

         file: cache/cord-014687-0am4l5ms.json
          key: cord-014687-0am4l5ms
      authors: nan
        title: SPR 2012
         date: 2012-03-29
      journal: Pediatr Radiol
          DOI: 10.1007/s00247-012-2356-8
          sha: 
       doc_id: 14687
     cord_uid: 0am4l5ms

         file: cache/cord-268088-y4vg7frb.json
          key: cord-268088-y4vg7frb
      authors: Montané, Xavier; Kowalczyk, Oliwia; Reig-Vano, Belen; Bajek, Anna; Roszkowski, Krzysztof; Tomczyk, Remigiusz; Pawliszak, Wojciech; Giamberini, Marta; Mocek-Płóciniak, Agnieszka; Tylkowski, Bartosz
        title: Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy
         date: 2020-07-23
      journal: Molecules
          DOI: 10.3390/molecules25153342
          sha: 
       doc_id: 268088
     cord_uid: y4vg7frb

         file: cache/cord-263074-qxiynbl2.json
          key: cord-263074-qxiynbl2
      authors: Nabi, Bushra; Rehman, Saleha; Aggarwal, Sumit; Baboota, Sanjula; Ali, Javed
        title: Nano-based anti-tubercular drug delivery: an emerging paradigm for improved therapeutic intervention
         date: 2020-05-16
      journal: Drug Deliv Transl Res
          DOI: 10.1007/s13346-020-00786-5
          sha: 
       doc_id: 263074
     cord_uid: qxiynbl2

         file: cache/cord-273941-gu6nnv9d.json
          key: cord-273941-gu6nnv9d
      authors: Chandran, Uma; Mehendale, Neelay; Patil, Saniya; Chaguturu, Rathnam; Patwardhan, Bhushan
        title: Chapter 5 Network Pharmacology
         date: 2017-12-31
      journal: Innovative Approaches in Drug Discovery
          DOI: 10.1016/b978-0-12-801814-9.00005-2
          sha: 
       doc_id: 273941
     cord_uid: gu6nnv9d

         file: cache/cord-265699-0socw0hp.json
          key: cord-265699-0socw0hp
      authors: Ortega, Miguel Ángel; Guzmán Merino, Alberto; Fraile-Martínez, Oscar; Recio-Ruiz, Judith; Pekarek, Leonel; G. Guijarro, Luis; García-Honduvilla, Natalio; Álvarez-Mon, Melchor; Buján, Julia; García-Gallego, Sandra
        title: Dendrimers and Dendritic Materials: From Laboratory to Medical Practice in Infectious Diseases
         date: 2020-09-14
      journal: Pharmaceutics
          DOI: 10.3390/pharmaceutics12090874
          sha: 
       doc_id: 265699
     cord_uid: 0socw0hp

         file: cache/cord-273716-vv3pyft4.json
          key: cord-273716-vv3pyft4
      authors: Khosravi-Darani, Kianoush; Pardakhty, Abbas; Honarpisheh, Hamid; Rao, V.S.N. Malleswara; Mozafari, M. Reza
        title: The role of high-resolution imaging in the evaluation of nanosystems for bioactive encapsulation and targeted nanotherapy
         date: 2007-07-03
      journal: Micron
          DOI: 10.1016/j.micron.2007.06.009
          sha: 
       doc_id: 273716
     cord_uid: vv3pyft4

         file: cache/cord-272060-o0wx0add.json
          key: cord-272060-o0wx0add
      authors: Li, Allen; Li, Ming K.; Crowther, Mark; Vazquez, Sara R.
        title: Drug-drug interactions affecting drug levels of direct oral anticoagulants in the real world: A systematic review()
         date: 2020-08-11
      journal: Thromb Res
          DOI: 10.1016/j.thromres.2020.08.016
          sha: 
       doc_id: 272060
     cord_uid: o0wx0add

         file: cache/cord-277535-u283k70i.json
          key: cord-277535-u283k70i
      authors: Vaja, Rakesh; Rana, Meenal
        title: Drugs and the liver
         date: 2020-09-22
      journal: nan
          DOI: 10.1016/j.mpaic.2020.07.001
          sha: 
       doc_id: 277535
     cord_uid: u283k70i

         file: cache/cord-276886-vcmkz8lh.json
          key: cord-276886-vcmkz8lh
      authors: Mandsberg, Nikolaj Kofoed; Christfort, Juliane Fjelrad; Kamguyan, Khorshid; Boisen, Anja; Srivastava, Sarvesh Kumar
        title: Orally ingestible medical devices for gut engineering
         date: 2020-05-13
      journal: Adv Drug Deliv Rev
          DOI: 10.1016/j.addr.2020.05.004
          sha: 
       doc_id: 276886
     cord_uid: vcmkz8lh

         file: cache/cord-275827-r86ygqmy.json
          key: cord-275827-r86ygqmy
      authors: Lapeyre-Mestre, Maryse; Boucher, Alexandra; Daveluy, Amelie; Gibaja, Valerie; Jouanjus, Emilie; Mallaret, Michel; Peyrière, Helene; Micallef, Joëlle
        title: Addictovigilance contribution during COVID-19 epidemic and lockdown in France
         date: 2020-06-23
      journal: Therapie
          DOI: 10.1016/j.therap.2020.06.006
          sha: 
       doc_id: 275827
     cord_uid: r86ygqmy

         file: cache/cord-279106-3ffa9djf.json
          key: cord-279106-3ffa9djf
      authors: Syatila Ab Ghani, Nur; Emrizal, Reeki; Makmur, Haslina; Firdaus-Raih, Mohd
        title: Side chain similarity comparisons for integrated drug repositioning and potential toxicity assessments in epidemic response scenarios: the case for COVID-19
         date: 2020-10-21
      journal: Comput Struct Biotechnol J
          DOI: 10.1016/j.csbj.2020.10.013
          sha: 
       doc_id: 279106
     cord_uid: 3ffa9djf

         file: cache/cord-275772-pmf6stua.json
          key: cord-275772-pmf6stua
      authors: Jourdan, Jean‐Pierre; Bureau, Ronan; Rochais, Christophe; Dallemagne, Patrick
        title: Drug repositioning: a brief overview
         date: 2020-04-17
      journal: J Pharm Pharmacol
          DOI: 10.1111/jphp.13273
          sha: 
       doc_id: 275772
     cord_uid: pmf6stua

         file: cache/cord-280819-z6ucnwk0.json
          key: cord-280819-z6ucnwk0
      authors: Achilonu, Ikechukwu; Iwuchukwu, Emmanuel Amarachi; Achilonu, Okechinyere Juliet; Fernandes, Manuel Antonio; Sayed, Yasien
        title: Targeting the SARS-CoV-2 main protease using FDA-approved Isavuconazonium, a P2-P3 α-ketoamide derivative and Pentagastrin: an in-silico drug discovery approach
         date: 2020-09-02
      journal: J Mol Graph Model
          DOI: 10.1016/j.jmgm.2020.107730
          sha: 
       doc_id: 280819
     cord_uid: z6ucnwk0

         file: cache/cord-284208-8fsqgkw5.json
          key: cord-284208-8fsqgkw5
      authors: Zolla, Lello
        title: Proteomics studies reveal important information on small molecule therapeutics: a case study on plasma proteins
         date: 2008-11-07
      journal: Drug Discov Today
          DOI: 10.1016/j.drudis.2008.09.013
          sha: 
       doc_id: 284208
     cord_uid: 8fsqgkw5

         file: cache/cord-281561-r10y2sgb.json
          key: cord-281561-r10y2sgb
      authors: Tiwari, Nidhi; Upadhyay, Jyoti; Nazam Ansari, Mohd; Joshi, Rohit
        title: Novel β-Coronavirus (SARS-CoV-2): Current and Future Aspects of Pharmacological Treatments
         date: 2020-08-27
      journal: Saudi Pharm J
          DOI: 10.1016/j.jsps.2020.08.015
          sha: 
       doc_id: 281561
     cord_uid: r10y2sgb

         file: cache/cord-274401-pjyvg53w.json
          key: cord-274401-pjyvg53w
      authors: Hrkach, Jeff; Langer, Robert
        title: From micro to nano: evolution and impact of drug delivery in treating disease
         date: 2020-05-08
      journal: Drug Deliv Transl Res
          DOI: 10.1007/s13346-020-00769-6
          sha: 
       doc_id: 274401
     cord_uid: pjyvg53w

         file: cache/cord-274474-u2fdicgz.json
          key: cord-274474-u2fdicgz
      authors: Majumder, Joydeb; Minko, Tamara
        title: Targeted Nanotherapeutics for Respiratory Diseases: Cancer, Fibrosis, and Coronavirus
         date: 2020-10-13
      journal: Adv Ther (Weinh)
          DOI: 10.1002/adtp.202000203
          sha: 
       doc_id: 274474
     cord_uid: u2fdicgz

         file: cache/cord-280158-3fhhuzg5.json
          key: cord-280158-3fhhuzg5
      authors: Hoffman, Paul S.
        title: Antibacterial Discovery: 21st Century Challenges
         date: 2020-04-28
      journal: Antibiotics (Basel)
          DOI: 10.3390/antibiotics9050213
          sha: 
       doc_id: 280158
     cord_uid: 3fhhuzg5

         file: cache/cord-283956-zgrtux7i.json
          key: cord-283956-zgrtux7i
      authors: Amin, Sk. Abdul; Jha, Tarun
        title: Fight against novel coronavirus: A perspective of medicinal chemists
         date: 2020-06-12
      journal: Eur J Med Chem
          DOI: 10.1016/j.ejmech.2020.112559
          sha: 
       doc_id: 283956
     cord_uid: zgrtux7i

         file: cache/cord-270622-aofva2ab.json
          key: cord-270622-aofva2ab
      authors: Li, Qizhang; Wang, Zhiying; Zheng, Qiang; Liu, Sen
        title: Potential clinical drugs as covalent inhibitors of the priming proteases of the spike protein of SARS-CoV-2
         date: 2020-08-26
      journal: Comput Struct Biotechnol J
          DOI: 10.1016/j.csbj.2020.08.016
          sha: 
       doc_id: 270622
     cord_uid: aofva2ab

         file: cache/cord-278362-pwi48i20.json
          key: cord-278362-pwi48i20
      authors: Khan, Abbas; Ali, Syed Shujait; Khan, Muhammad Tahir; Saleem, Shoaib; Ali, Arif; Suleman, Muhammad; Babar, Zainib; Shafiq, Athar; Khan, Mazhar; Wei, Dong-Qing
        title: Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro)
         date: 2020-06-18
      journal: J Biomol Struct Dyn
          DOI: 10.1080/07391102.2020.1779128
          sha: 
       doc_id: 278362
     cord_uid: pwi48i20

         file: cache/cord-285121-3cjr1rol.json
          key: cord-285121-3cjr1rol
      authors: Chan, Marion M.; Chen, Rensa; Fong, Dunne
        title: Targeting cancer stem cells with dietary phytochemical - Repositioned drug combinations
         date: 2018-10-01
      journal: Cancer Lett
          DOI: 10.1016/j.canlet.2018.06.034
          sha: 
       doc_id: 285121
     cord_uid: 3cjr1rol

         file: cache/cord-257496-mirh80gn.json
          key: cord-257496-mirh80gn
      authors: Hickey, Anthony J.
        title: Emerging trends in inhaled drug delivery
         date: 2020-07-12
      journal: Adv Drug Deliv Rev
          DOI: 10.1016/j.addr.2020.07.006
          sha: 
       doc_id: 257496
     cord_uid: mirh80gn

         file: cache/cord-284479-75zgljet.json
          key: cord-284479-75zgljet
      authors: García-Serradilla, Moisés; Risco, Cristina; Pacheco, Beatriz
        title: Drug repurposing for new, efficient, broad spectrum antivirals
         date: 2019-04-15
      journal: Virus Res
          DOI: 10.1016/j.virusres.2019.02.011
          sha: 
       doc_id: 284479
     cord_uid: 75zgljet

         file: cache/cord-289321-ahl46ql9.json
          key: cord-289321-ahl46ql9
      authors: van Buuren, Nicholas; Tellinghuisen, Timothy L; Richardson, Christopher D; Kirkegaard, Karla
        title: Transmission genetics of drug-resistant hepatitis C virus
         date: 2018-03-28
      journal: eLife
          DOI: 10.7554/elife.32579
          sha: 
       doc_id: 289321
     cord_uid: ahl46ql9

         file: cache/cord-289382-bnl9i9oy.json
          key: cord-289382-bnl9i9oy
      authors: Wright, Gerard D
        title: Q&A: Antibiotic resistance: where does it come from and what can we do about it?
         date: 2010-09-20
      journal: BMC Biol
          DOI: 10.1186/1741-7007-8-123
          sha: 
       doc_id: 289382
     cord_uid: bnl9i9oy

         file: cache/cord-293860-6kz0iws6.json
          key: cord-293860-6kz0iws6
      authors: Qutayba Almerie, Muhammad; Daniel Kerrigan, David
        title: The Association between Obesity and Poor Outcome after COVID-19 Indicates a Potential Therapeutic Role for Montelukast
         date: 2020-05-27
      journal: Med Hypotheses
          DOI: 10.1016/j.mehy.2020.109883
          sha: 
       doc_id: 293860
     cord_uid: 6kz0iws6

         file: cache/cord-299225-exbdg3x9.json
          key: cord-299225-exbdg3x9
      authors: Guarnieri, Michael; Brayton, Cory; Tyler, Betty M.
        title: A Long-Term Study of a Lipid-Buprenorphine Implant in Rats
         date: 2018-07-09
      journal: J Vet Med
          DOI: 10.1155/2018/2616152
          sha: 
       doc_id: 299225
     cord_uid: exbdg3x9

         file: cache/cord-288026-vcp8o5xn.json
          key: cord-288026-vcp8o5xn
      authors: DeStefano, Vincent; Khan, Salaar; Tabada, Alonzo
        title: Applications of PLA in Modern Medicine
         date: 2020-09-06
      journal: nan
          DOI: 10.1016/j.engreg.2020.08.002
          sha: 
       doc_id: 288026
     cord_uid: vcp8o5xn

         file: cache/cord-302947-flgwxc57.json
          key: cord-302947-flgwxc57
      authors: Kipshidze, Nicholas; Iversen, Patrick; Porter, Thomas R.; Kipshidze, Nodar; Siddiqui, Fakiha; Dangas, George; Fareed, Jawed
        title: Targeted, Site-Specific, Delivery Vehicles of Therapeutics for COVID-19 Patients. Brief Review
         date: 2020-09-16
      journal: Clin Appl Thromb Hemost
          DOI: 10.1177/1076029620954911
          sha: 
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          key: cord-294582-flkjekyo
      authors: Hijikata, Atsushi; Shionyu‐Mitsuyama, Clara; Nakae, Setsu; Shionyu, Masafumi; Ota, Motonori; Kanaya, Shigehiko; Shirai, Tsuyoshi
        title: Knowledge‐based structural models of SARS‐CoV‐2 proteins and their complexes with potential drugs
         date: 2020-05-25
      journal: FEBS Lett
          DOI: 10.1002/1873-3468.13806
          sha: 
       doc_id: 294582
     cord_uid: flkjekyo

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          key: cord-285603-f4572w5m
      authors: Ortega, Joseph T.; Serrano, Maria Luisa; Jastrzebska, Beata
        title: Class A G Protein-Coupled Receptor Antagonist Famotidine as a Therapeutic Alternative against SARS-CoV2: An In Silico Analysis
         date: 2020-06-24
      journal: Biomolecules
          DOI: 10.3390/biom10060954
          sha: 
       doc_id: 285603
     cord_uid: f4572w5m

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          key: cord-303089-fbxtj8ij
      authors: Boccaletti, Valeria; Cortelazzi, Chiara; Fantini, Carolina; Tognetti, Elena; Fabrizi, Giuseppe; Pagliarello, Calogero; Di Nuzzo, Sergio
        title: Acute generalized exanthematous pustulosis following paracetamol ingestion in a child
         date: 2015-05-24
      journal: Pediatr Allergy Immunol
          DOI: 10.1111/pai.12386
          sha: 
       doc_id: 303089
     cord_uid: fbxtj8ij

         file: cache/cord-292041-a65kfw80.json
          key: cord-292041-a65kfw80
      authors: Orienti, Isabella; Gentilomi, Giovanna Angela; Farruggia, Giovanna
        title: Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment in COVID-19
         date: 2020-05-27
      journal: Int J Mol Sci
          DOI: 10.3390/ijms21113812
          sha: 
       doc_id: 292041
     cord_uid: a65kfw80

         file: cache/cord-302018-3rlya16w.json
          key: cord-302018-3rlya16w
      authors: Castells, Mariana C.
        title: Drug allergy labeling and delabeling in the coronavirus disease 2019 era: What is important and what do we need to know
         date: 2020-05-22
      journal: Ann Allergy Asthma Immunol
          DOI: 10.1016/j.anai.2020.04.012
          sha: 
       doc_id: 302018
     cord_uid: 3rlya16w

         file: cache/cord-298369-66ifwtlp.json
          key: cord-298369-66ifwtlp
      authors: Smith, Sherri A.; Waters, Nigel J.
        title: Pharmacokinetic and Pharmacodynamic Considerations for Drugs Binding to Alpha-1-Acid Glycoprotein
         date: 2018-12-28
      journal: Pharm Res
          DOI: 10.1007/s11095-018-2551-x
          sha: 
       doc_id: 298369
     cord_uid: 66ifwtlp

         file: cache/cord-287758-da11ypiy.json
          key: cord-287758-da11ypiy
      authors: Mônica Vitalino de Almeida, Sinara; Cleberson Santos Soares, José; Lima dos Santos, Keriolaine; Emanuel Ferreira Alves, Josival; Galdino Ribeiro, Amélia; Trindade Tenório Jacob, Íris; Juliane da Silva Ferreira, Cindy; Celerino dos Santos, Jéssica; Ferreira de Oliveira, Jamerson; Bezerra de Carvalho Junior, Luiz; do Carmo Alves de Lima, Maria
        title: COVID-19 therapy: what weapons do we bring into battle?
         date: 2020-09-10
      journal: Bioorg Med Chem
          DOI: 10.1016/j.bmc.2020.115757
          sha: 
       doc_id: 287758
     cord_uid: da11ypiy

         file: cache/cord-284648-yznlgzir.json
          key: cord-284648-yznlgzir
      authors: Varanko, Anastasia; Saha, Soumen; Chilkoti, Ashutosh
        title: Recent trends in protein and peptide-based biomaterials for advanced drug delivery
         date: 2020-08-29
      journal: Adv Drug Deliv Rev
          DOI: 10.1016/j.addr.2020.08.008
          sha: 
       doc_id: 284648
     cord_uid: yznlgzir

         file: cache/cord-275828-c6d6nk7x.json
          key: cord-275828-c6d6nk7x
      authors: Mikasa, Keiichi; Aoki, Nobuki; Aoki, Yosuke; Abe, Shuichi; Iwata, Satoshi; Ouchi, Kazunobu; Kasahara, Kei; Kadota, Junichi; Kishida, Naoki; Kobayashi, Osamu; Sakata, Hiroshi; Seki, Masahumi; Tsukada, Hiroki; Tokue, Yutaka; Nakamura-Uchiyama, Fukumi; Higa, Futoshi; Maeda, Koichi; Yanagihara, Katsunori; Yoshida, Koichiro
        title: JAID/JSC Guidelines for the Treatment of Respiratory Infectious Diseases: The Japanese Association for Infectious Diseases/Japanese Society of Chemotherapy – The JAID/JSC Guide to Clinical Management of Infectious Disease/Guideline-preparing Committee Respiratory Infectious Disease WG
         date: 2016-07-31
      journal: Journal of Infection and Chemotherapy
          DOI: 10.1016/j.jiac.2015.12.019
          sha: 
       doc_id: 275828
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         file: cache/cord-301026-spgidqh3.json
          key: cord-301026-spgidqh3
      authors: Das, Shaoli; Camphausen, Kevin; Shankavaram, Uma
        title: In silico Drug Repurposing to combat COVID-19 based on Pharmacogenomics of Patient Transcriptomic Data
         date: 2020-06-30
      journal: Res Sq
          DOI: 10.21203/rs.3.rs-39128/v1
          sha: 
       doc_id: 301026
     cord_uid: spgidqh3

         file: cache/cord-303555-mwu72q7w.json
          key: cord-303555-mwu72q7w
      authors: Dent, Paul
        title: Cell Signaling and Translational Developmental Therapeutics
         date: 2020-10-06
      journal: Reference Module in Chemistry, Molecular Sciences and Chemical Engineering
          DOI: 10.1016/b978-0-12-820472-6.00002-5
          sha: 
       doc_id: 303555
     cord_uid: mwu72q7w

         file: cache/cord-302312-1pm17l5d.json
          key: cord-302312-1pm17l5d
      authors: Quinteros, Daniela A.; Bermúdez, José M.; Ravetti, Soledad; Cid, Alicia; Allemandi, Daniel A.; Palma, Santiago D.
        title: Therapeutic use of monoclonal antibodies: general aspects and challenges for drug delivery
         date: 2017-03-31
      journal: Nanostructures for Drug Delivery
          DOI: 10.1016/b978-0-323-46143-6.00025-7
          sha: 
       doc_id: 302312
     cord_uid: 1pm17l5d

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          key: cord-299911-v95pf3eg
      authors: El-Ghiaty, Mahmoud A.; Shoieb, Sherif M.; El-Kadi, Ayman O.S.
        title: Cytochrome P450-mediated drug interactions in COVID-19 patients: current findings and possible mechanisms
         date: 2020-06-26
      journal: Med Hypotheses
          DOI: 10.1016/j.mehy.2020.110033
          sha: 
       doc_id: 299911
     cord_uid: v95pf3eg

         file: cache/cord-297010-imciixde.json
          key: cord-297010-imciixde
      authors: Babayeva, Mariana; Loewy, Zvi
        title: Repurposing Drugs for COVID-19: Pharmacokinetics and Pharmacogenomics of Chloroquine and Hydroxychloroquine
         date: 2020-10-23
      journal: Pharmgenomics Pers Med
          DOI: 10.2147/pgpm.s275964
          sha: 
       doc_id: 297010
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         file: cache/cord-303865-vd3qr32o.json
          key: cord-303865-vd3qr32o
      authors: Gianturco, Stephanie L.; Yoon, SeJeong; Yuen, Melissa V.; Mattingly, Ashlee N.
        title: Outsourcing facilities and their place in the U.S. drug supply chain
         date: 2020-08-28
      journal: J Am Pharm Assoc (2003)
          DOI: 10.1016/j.japh.2020.07.021
          sha: 
       doc_id: 303865
     cord_uid: vd3qr32o

         file: cache/cord-291180-xurmzmwj.json
          key: cord-291180-xurmzmwj
      authors: Lin, Xiaoqian; Li, Xiu; Lin, Xubo
        title: A Review on Applications of Computational Methods in Drug Screening and Design
         date: 2020-03-18
      journal: Molecules
          DOI: 10.3390/molecules25061375
          sha: 
       doc_id: 291180
     cord_uid: xurmzmwj

         file: cache/cord-303237-xvba5mqq.json
          key: cord-303237-xvba5mqq
      authors: Wang, L.-Y.; Cui, J.-J.; OuYang, Q.-Y.; Zhan, Y.; Wang, Y.-M.; Xu, X.-Y.; Guo, C.-X.; Yin, J.
        title: Genetic Profiles in Pharmacogenes Indicate Personalized Drug Therapy for COVID-19
         date: 2020-03-30
      journal: nan
          DOI: 10.1101/2020.03.23.20041350
          sha: 
       doc_id: 303237
     cord_uid: xvba5mqq

         file: cache/cord-318048-6nvi63rq.json
          key: cord-318048-6nvi63rq
      authors: Arshad, Usman; Pertinez, Henry; Box, Helen; Tatham, Lee; Rajoli, Rajith KR; Curley, Paul; Neary, Megan; Sharp, Joanne; Liptrott, Neill J; Valentijn, Anthony; David, Christopher; Rannard, Steve P; O’Neill, Paul M; Aljayyoussi, Ghaith; Pennington, Shaun; Ward, Stephen A; Hill, Andrew; Back, David J; Khoo, Saye H; Bray, Patrick G; Biagini, Giancarlo A; Owen, Andrew
        title: Prioritisation of Anti‐SARS‐Cov‐2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics
         date: 2020-05-21
      journal: Clin Pharmacol Ther
          DOI: 10.1002/cpt.1909
          sha: 
       doc_id: 318048
     cord_uid: 6nvi63rq

         file: cache/cord-298033-kzdp9edn.json
          key: cord-298033-kzdp9edn
      authors: Domingo, Esteban
        title: Quasispecies dynamics in disease prevention and control
         date: 2019-11-08
      journal: Virus as Populations
          DOI: 10.1016/b978-0-12-816331-3.00008-8
          sha: 
       doc_id: 298033
     cord_uid: kzdp9edn

         file: cache/cord-314827-yqr7110e.json
          key: cord-314827-yqr7110e
      authors: Attia, Yasmeen M.; Ewida, Heba; Ahmed, Mahmoud Salama
        title: Successful stories of drug repurposing for cancer therapy in hepatocellular carcinoma
         date: 2020-09-04
      journal: Drug Repurposing in Cancer Therapy
          DOI: 10.1016/b978-0-12-819668-7.00008-7
          sha: 
       doc_id: 314827
     cord_uid: yqr7110e

         file: cache/cord-317435-4yuw7jo3.json
          key: cord-317435-4yuw7jo3
      authors: Zhou, Yadi; Hou, Yuan; Shen, Jiayu; Huang, Yin; Martin, William; Cheng, Feixiong
        title: Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2
         date: 2020-03-16
      journal: Cell Discov
          DOI: 10.1038/s41421-020-0153-3
          sha: 
       doc_id: 317435
     cord_uid: 4yuw7jo3

         file: cache/cord-006229-7yoilsho.json
          key: cord-006229-7yoilsho
      authors: nan
        title: Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH)
         date: 2016-02-06
      journal: Naunyn Schmiedebergs Arch Pharmacol
          DOI: 10.1007/s00210-016-1213-y
          sha: 
       doc_id: 6229
     cord_uid: 7yoilsho

         file: cache/cord-299400-j18pj11d.json
          key: cord-299400-j18pj11d
      authors: Norinder, Ulf; Tuck, Astrud; Norgren, Kalle; Kos, Vesna Munic
        title: Existing highly accumulating lysosomotropic drugs with potential for repurposing to target COVID-19
         date: 2020-07-30
      journal: Biomed Pharmacother
          DOI: 10.1016/j.biopha.2020.110582
          sha: 
       doc_id: 299400
     cord_uid: j18pj11d

         file: cache/cord-299424-qy3lccjq.json
          key: cord-299424-qy3lccjq
      authors: MUBAGWA, Kanigula
        title: Chloroquine cardiac effects and toxicity.A short update.
         date: 2020-06-19
      journal: Int J Antimicrob Agents
          DOI: 10.1016/j.ijantimicag.2020.106057
          sha: 
       doc_id: 299424
     cord_uid: qy3lccjq

         file: cache/cord-309025-jo0rqy3y.json
          key: cord-309025-jo0rqy3y
      authors: Maurya, Priyanka; Singh, Samipta; Saraf, Shubhini A.
        title: Inhalable hybrid nanocarriers for respiratory disorders
         date: 2020-09-18
      journal: Targeting Chronic Inflammatory Lung Diseases Using Advanced Drug Delivery Systems
          DOI: 10.1016/b978-0-12-820658-4.00013-3
          sha: 
       doc_id: 309025
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         file: cache/cord-295807-68sukdb1.json
          key: cord-295807-68sukdb1
      authors: Quade, Bianca N.; Parker, Mark D.; Occhipinti, Rossana
        title: The therapeutic importance of acid-base balance
         date: 2020-10-09
      journal: Biochem Pharmacol
          DOI: 10.1016/j.bcp.2020.114278
          sha: 
       doc_id: 295807
     cord_uid: 68sukdb1

         file: cache/cord-317993-012hx4kc.json
          key: cord-317993-012hx4kc
      authors: Movia, Dania; Prina-Mello, Adriele
        title: Preclinical Development of Orally Inhaled Drugs (OIDs)—Are Animal Models Predictive or Shall We Move Towards In Vitro Non-Animal Models?
         date: 2020-07-24
      journal: Animals (Basel)
          DOI: 10.3390/ani10081259
          sha: 
       doc_id: 317993
     cord_uid: 012hx4kc

         file: cache/cord-308994-4nljzm8a.json
          key: cord-308994-4nljzm8a
      authors: Tang, Zhongmin; Zhang, Xingcai; Shu, Yiqing; Guo, Ming; Zhang, Han; Tao, Wei
        title: Insights from nanotechnology in COVID-19 treatment
         date: 2020-11-04
      journal: Nano Today
          DOI: 10.1016/j.nantod.2020.101019
          sha: 
       doc_id: 308994
     cord_uid: 4nljzm8a

         file: cache/cord-321267-ihd30qi0.json
          key: cord-321267-ihd30qi0
      authors: Daughton, Christian G.
        title: Natural experiment concept to accelerate the Re-purposing of existing therapeutics for Covid-19
         date: 2020-05-15
      journal: Glob Epidemiol
          DOI: 10.1016/j.gloepi.2020.100026
          sha: 
       doc_id: 321267
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         file: cache/cord-326922-bajpr5a2.json
          key: cord-326922-bajpr5a2
      authors: Watson, C. James; Whitledge, James D.; Siani, Alicia M.; Burns, Michele M.
        title: Pharmaceutical Compounding: a History, Regulatory Overview, and Systematic Review of Compounding Errors
         date: 2020-11-02
      journal: J Med Toxicol
          DOI: 10.1007/s13181-020-00814-3
          sha: 
       doc_id: 326922
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         file: cache/cord-304617-5ozf18lg.json
          key: cord-304617-5ozf18lg
      authors: Al-Khafaji, Khattab; AL-DuhaidahawiL, Dunya; Taskin Tok, Tugba
        title: Using integrated computational approaches to identify safe and rapid treatment for SARS-CoV-2
         date: 2020-05-15
      journal: J Biomol Struct Dyn
          DOI: 10.1080/07391102.2020.1764392
          sha: 
       doc_id: 304617
     cord_uid: 5ozf18lg

         file: cache/cord-315918-12rbbe8c.json
          key: cord-315918-12rbbe8c
      authors: Mukherjee, Pulok K.
        title: Antiviral Evaluation of Herbal Drugs
         date: 2019-06-21
      journal: Quality Control and Evaluation of Herbal Drugs
          DOI: 10.1016/b978-0-12-813374-3.00016-8
          sha: 
       doc_id: 315918
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         file: cache/cord-316792-89f8g0m8.json
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      authors: Herzig, Volker; Cristofori-Armstrong, Ben; Israel, Mathilde R.; Nixon, Samantha A.; Vetter, Irina; King, Glenn F.
        title: Animal toxins — Nature’s evolutionary-refined toolkit for basic research and drug discovery
         date: 2020-06-12
      journal: Biochem Pharmacol
          DOI: 10.1016/j.bcp.2020.114096
          sha: 
       doc_id: 316792
     cord_uid: 89f8g0m8

         file: cache/cord-316029-z708c3ex.json
          key: cord-316029-z708c3ex
      authors: Brunsdon, Priya; Saluja, Bhawana; Sahajwalla, Chandrahas
        title: Clinical Pharmacology Considerations for Developing Small‐Molecule Treatments for COVID‐19
         date: 2020-07-12
      journal: J Clin Pharmacol
          DOI: 10.1002/jcph.1697
          sha: 
       doc_id: 316029
     cord_uid: z708c3ex

         file: cache/cord-317971-kuwargnp.json
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      authors: Opatz, Till; Senn‐Bilfinger, Joerg; Richert, Clemens
        title: Thoughts on What Chemists Can Contribute to Fighting SARS‐CoV‐2 – A Short Note on Hand Sanitizers, Drug Candidates and Outreach
         date: 2020-05-08
      journal: Angew Chem Int Ed Engl
          DOI: 10.1002/anie.202004721
          sha: 
       doc_id: 317971
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      authors: Scherrmann, JM.
        title: Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy
         date: 2020-06-12
      journal: AAPS J
          DOI: 10.1208/s12248-020-00465-w
          sha: 
       doc_id: 309871
     cord_uid: y17puao2

         file: cache/cord-322885-ob5euspo.json
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      authors: Durdagi, Serdar; Dag, Cagdas; Dogan, Berna; Yigin, Merve; Avsar, Timucin; Buyukdag, Cengizhan; Erol, Ismail; Ertem, Betul; Calis, Seyma; Yildirim, Gunseli; Orhan, Muge D.; Guven, Omur; Aksoydan, Busecan; Destan, Ebru; Sahin, Kader; Besler, Sabri O.; Oktay, Lalehan; Shafiei, Alaleh; Tolu, Ilayda; Ayan, Esra; Yuksel, Busra; Peksen, Ayse B.; Gocenler, Oktay; Yucel, Ali D.; Can, Ozgur; Ozabrahamyan, Serena; Olkan, Alpsu; Erdemoglu, Ece; Aksit, Fulya; Tanisali, Gokhan; Yefanov, Oleksandr M.; Barty, Anton; Tolstikova, Alexandra; Ketawala, Gihan K.; Botha, Sabine; Dao, E. Han; Hayes, Brandon; Liang, Mengning; Seaberg, Matthew H.; Hunter, Mark S.; Batyuk, Alex; Mariani, Valerio; Su, Zhen; Poitevin, Frederic; Yoon, Chun Hong; Kupitz, Christopher; Sierra, Raymond G.; Snell, Edward; DeMirci, Hasan
        title: Near-Physiological-Temperature Serial Femtosecond X-ray Crystallography Reveals Novel Conformations of SARS-CoV-2 Main Protease Active Site for Improved Drug Repurposing
         date: 2020-09-09
      journal: bioRxiv
          DOI: 10.1101/2020.09.09.287987
          sha: 
       doc_id: 322885
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      authors: Becker, Richard C.
        title: Covid-19 treatment update: follow the scientific evidence
         date: 2020-04-27
      journal: J Thromb Thrombolysis
          DOI: 10.1007/s11239-020-02120-9
          sha: 
       doc_id: 311730
     cord_uid: 189vax2m

         file: cache/cord-321379-7bpl5n3j.json
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      authors: Singh, Sweta; Florez, Hector
        title: Coronavirus disease 2019 drug discovery through molecular docking
         date: 2020-06-03
      journal: F1000Res
          DOI: 10.12688/f1000research.24218.1
          sha: 
       doc_id: 321379
     cord_uid: 7bpl5n3j

         file: cache/cord-325019-hznnoxw6.json
          key: cord-325019-hznnoxw6
      authors: Benavides-Cordoba, Vicente
        title: Drug Repositioning for COVID-19
         date: 2020-06-30
      journal: Colombia medica
          DOI: 10.25100/cm.v51i2.4279
          sha: 
       doc_id: 325019
     cord_uid: hznnoxw6

         file: cache/cord-321741-aq76s37x.json
          key: cord-321741-aq76s37x
      authors: Andersen, Petter I.; Ianevski, Aleksandr; Lysvand, Hilde; Vitkauskiene, Astra; Oksenych, Valentyn; Bjørås, Magnar; Telling, Kaidi; Lutsar, Irja; Dumpis, Uga; Irie, Yasuhiko; Tenson, Tanel; Kantele, Anu; Kainov, Denis E.
        title: Discovery and development of safe-in-man broad-spectrum antiviral agents
         date: 2020-04-30
      journal: International Journal of Infectious Diseases
          DOI: 10.1016/j.ijid.2020.02.018
          sha: 
       doc_id: 321741
     cord_uid: aq76s37x

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          key: cord-315702-pn8247j2
      authors: Sahakijpijarn, Sawittree; Moon, Chaeho; Koleng, John J.; Christensen, Dale J.; Williams, Robert O.
        title: Development of Remdesivir as a Dry Powder for Inhalation by Thin Film Freezing
         date: 2020-09-22
      journal: bioRxiv
          DOI: 10.1101/2020.07.26.222109
          sha: 
       doc_id: 315702
     cord_uid: pn8247j2

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      authors: Samji, Hasina; Yu, Amanda; Wong, Stanley; Wilton, James; Binka, Mawuena; Alvarez, Maria; Bartlett, Sofia; Pearce, Margo; Adu, Prince; Jeong, Dahn; Clementi, Emilia; Butt, Zahid; Buxton, Jane; Gilbert, Mark; Krajden, Mel; Janjua, Naveed Z.
        title: Drug-related deaths in a population-level cohort of people living with and without hepatitis C virus in British Columbia, Canada
         date: 2020-10-19
      journal: Int J Drug Policy
          DOI: 10.1016/j.drugpo.2020.102989
          sha: 
       doc_id: 321230
     cord_uid: b5a1z14w

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      authors: Kumar, Neeraj; Awasthi, Amardeep; Kumari, Anchala; Sood, Damini; Jain, Pallavi; Singh, Taru; Sharma, Neera; Grover, Abhinav; Chandra, Ramesh
        title: Antitussive noscapine and antiviral drug conjugates as arsenal against COVID-19: a comprehensive chemoinformatics analysis
         date: 2020-08-20
      journal: Journal of biomolecular structure & dynamics
          DOI: 10.1080/07391102.2020.1808072
          sha: 
       doc_id: 324166
     cord_uid: 6ydn2bvy

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      authors: Rossi, Carlo Maria; Beretta, Flavio Niccolò; Traverso, Grazia; Mancarella, Sandro; Zenoni, Davide
        title: A case report of toxic epidermal necrolysis (TEN) in a patient with COVID-19 treated with hydroxychloroquine: are these two partners in crime?
         date: 2020-10-06
      journal: Clin Mol Allergy
          DOI: 10.1186/s12948-020-00133-6
          sha: 
       doc_id: 325315
     cord_uid: m3do6t1j

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      authors: Du, Sean Quan; Yuan, Weiming
        title: Mathematical modeling of interaction between innate and adaptive immune responses in COVID‐19 and implications for viral pathogenesis
         date: 2020-05-13
      journal: J Med Virol
          DOI: 10.1002/jmv.25866
          sha: 
       doc_id: 321657
     cord_uid: 2s1npse5

         file: cache/cord-332271-slouuryl.json
          key: cord-332271-slouuryl
      authors: Baker, Jeremy D.; Uhrich, Rikki L.; Kraemer, Gerald C.; Love, Jason E.; Kraemer, Brian C.
        title: A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV-2 main protease
         date: 2020-08-27
      journal: bioRxiv
          DOI: 10.1101/2020.07.10.197889
          sha: 
       doc_id: 332271
     cord_uid: slouuryl

         file: cache/cord-304506-6el2ryl8.json
          key: cord-304506-6el2ryl8
      authors: Watkins, Laura C.; DeGrado, William F.; Voth, Gregory A.
        title: Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics
         date: 2020-09-16
      journal: J Am Chem Soc
          DOI: 10.1021/jacs.0c06419
          sha: 
       doc_id: 304506
     cord_uid: 6el2ryl8

         file: cache/cord-328559-2qvxw896.json
          key: cord-328559-2qvxw896
      authors: LeSaint, Kathy T.; Snyder, Hannah R.
        title: Impact of Social Distancing on Individuals Who Use Drugs: Considerations for Emergency Department Providers
         date: 2020-08-18
      journal: West J Emerg Med
          DOI: 10.5811/westjem.2020.7.47896
          sha: 
       doc_id: 328559
     cord_uid: 2qvxw896

         file: cache/cord-325473-hrdanbn1.json
          key: cord-325473-hrdanbn1
      authors: Ghahremanpour, Mohammad M.; Tirado-Rives, Julian; Deshmukh, Maya; Ippolito, Joseph A.; Zhang, Chun-Hui; de Vaca, Israel Cabeza; Liosi, Maria-Elena; Anderson, Karen S.; Jorgensen, William L.
        title: Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2
         date: 2020-08-28
      journal: bioRxiv
          DOI: 10.1101/2020.08.28.271957
          sha: 
       doc_id: 325473
     cord_uid: hrdanbn1

         file: cache/cord-343620-64i1balq.json
          key: cord-343620-64i1balq
      authors: Darvishi, Behrad; Manoochehri, Saeed; Kamalinia, Golnaz; Samadi, Nasrin; Amini, Mohsen; Mostafavi, Seyyed Hossein; Maghazei, Shahab; Atyabi, Fatemeh; Dinarvand, Rassoul
        title: Preparation and Antibacterial Activity Evaluation of 18-β-glycyrrhetinic Acid Loaded PLGA Nanoparticles
         date: 2015
      journal: Iran J Pharm Res
          DOI: nan
          sha: 
       doc_id: 343620
     cord_uid: 64i1balq

         file: cache/cord-329881-9vnz5zzg.json
          key: cord-329881-9vnz5zzg
      authors: Garcia, Sònia
        title: Pandemics and Traditional Plant-Based Remedies. A Historical-Botanical Review in the Era of COVID19
         date: 2020-08-28
      journal: Front Plant Sci
          DOI: 10.3389/fpls.2020.571042
          sha: 
       doc_id: 329881
     cord_uid: 9vnz5zzg

         file: cache/cord-324660-w81jgw7p.json
          key: cord-324660-w81jgw7p
      authors: Guharoy, Roy
        title: Medication Shortages: A Matter of National Security—Time for Action
         date: 2020-08-01
      journal: Mayo Clin Proc
          DOI: 10.1016/j.mayocp.2020.06.025
          sha: 
       doc_id: 324660
     cord_uid: w81jgw7p

         file: cache/cord-334170-85x5vmyi.json
          key: cord-334170-85x5vmyi
      authors: Masoudi-Sobhanzadeh, Yosef; Masoudi-Nejad, Ali
        title: Synthetic repurposing of drugs against hypertension: a datamining method based on association rules and a novel discrete algorithm
         date: 2020-07-16
      journal: BMC Bioinformatics
          DOI: 10.1186/s12859-020-03644-w
          sha: 
       doc_id: 334170
     cord_uid: 85x5vmyi

         file: cache/cord-313268-j51zyodw.json
          key: cord-313268-j51zyodw
      authors: Zeng, Xiangxiang; Song, Xiang; Ma, Tengfei; Pan, Xiaoqin; Zhou, Yadi; Hou, Yuan; Zhang, Zheng; Li, Kenli; Karypis, George; Cheng, Feixiong
        title: Repurpose Open Data to Discover Therapeutics for COVID-19 Using Deep Learning
         date: 2020-07-12
      journal: J Proteome Res
          DOI: 10.1021/acs.jproteome.0c00316
          sha: 
       doc_id: 313268
     cord_uid: j51zyodw

         file: cache/cord-336554-n8n5ii5k.json
          key: cord-336554-n8n5ii5k
      authors: Singh, Thakur Uttam; Parida, Subhashree; Lingaraju, Madhu Cholenahalli; Kesavan, Manickam; Kumar, Dinesh; Singh, Raj Kumar
        title: Drug repurposing approach to fight COVID-19
         date: 2020-09-05
      journal: Pharmacol Rep
          DOI: 10.1007/s43440-020-00155-6
          sha: 
       doc_id: 336554
     cord_uid: n8n5ii5k

         file: cache/cord-331633-ix5un6c9.json
          key: cord-331633-ix5un6c9
      authors: Teixeira, Maria C.; Carbone, Claudia; Sousa, Maria C.; Espina, Marta; Garcia, Maria L.; Sanchez-Lopez, Elena; Souto, Eliana B.
        title: Nanomedicines for the Delivery of Antimicrobial Peptides (AMPs)
         date: 2020-03-20
      journal: Nanomaterials (Basel)
          DOI: 10.3390/nano10030560
          sha: 
       doc_id: 331633
     cord_uid: ix5un6c9

         file: cache/cord-334881-x9nxxled.json
          key: cord-334881-x9nxxled
      authors: Di Lorenzo, Giuseppe; Di Trolio, Rossella; Kozlakidis, Zisis; Busto, Giuseppina; Ingenito, Concetta; Buonerba, Luciana; Ferrara, Claudia; Libroia, Annamaria; Ragone, Gianluca; Ioio, Concetta dello; Savastano, Beatrice; Polverino, Mario; De Falco, Ferdinando; Iaccarino, Simona; Leo, Emilio
        title: COVID 19 therapies and anti-cancer drugs: A systematic review of recent literature
         date: 2020-05-21
      journal: Crit Rev Oncol Hematol
          DOI: 10.1016/j.critrevonc.2020.102991
          sha: 
       doc_id: 334881
     cord_uid: x9nxxled

         file: cache/cord-353524-3w970ycx.json
          key: cord-353524-3w970ycx
      authors: Dömling, Alexander; Gao, Li
        title: Chemistry and Biology of SARS-CoV-2
         date: 2020-05-22
      journal: Chem
          DOI: 10.1016/j.chempr.2020.04.023
          sha: 
       doc_id: 353524
     cord_uid: 3w970ycx

         file: cache/cord-328705-024y5k72.json
          key: cord-328705-024y5k72
      authors: Rahman, Md. Mahbubur; Saha, Titon; Islam, Kazi Jahidul; Suman, Rasel Hosen; Biswas, Sourav; Rahat, Emon Uddin; Hossen, Md. Rubel; Islam, Rajib; Hossain, Md Nayeem; Mamun, Abdulla Al; Khan, Maksud; Ali, Md Ackas; Halim, Mohammad A.
        title: Virtual screening, molecular dynamics and structure–activity relationship studies to identify potent approved drugs for Covid-19 treatment
         date: 2020-07-21
      journal: Journal of biomolecular structure & dynamics
          DOI: 10.1080/07391102.2020.1794974
          sha: 
       doc_id: 328705
     cord_uid: 024y5k72

         file: cache/cord-354180-6esn3t2b.json
          key: cord-354180-6esn3t2b
      authors: Tyndall, Mark
        title: Safer opioid distribution in response to the COVID-19 pandemic
         date: 2020-07-27
      journal: Int J Drug Policy
          DOI: 10.1016/j.drugpo.2020.102880
          sha: 
       doc_id: 354180
     cord_uid: 6esn3t2b

         file: cache/cord-322915-zrjx31ev.json
          key: cord-322915-zrjx31ev
      authors: Demain, Arnold L; Sanchez, Sergio
        title: Microbial drug discovery: 80 years of progress
         date: 2009-01-09
      journal: J Antibiot (Tokyo)
          DOI: 10.1038/ja.2008.16
          sha: 
       doc_id: 322915
     cord_uid: zrjx31ev

         file: cache/cord-348245-pf5mlzrw.json
          key: cord-348245-pf5mlzrw
      authors: Moura-Neto, José A.; Misael, Ana Maria; da Silva, Dirceu Reis; D’Avila, Ronaldo; Andreoli, Maria Claudia Cruz; Kraychete, Angiolina; Bastos, Kleyton; do Nascimento, Marcelo Mazza
        title: Position statement from the Brazilian Society of Nephrology regarding chloroquine and hydroxychloroquine drug dose adjustment according to renal function
         date: 2020-08-26
      journal: J Bras Nefrol
          DOI: 10.1590/2175-8239-jbn-2020-s113
          sha: 
       doc_id: 348245
     cord_uid: pf5mlzrw

         file: cache/cord-333381-wz70o9tt.json
          key: cord-333381-wz70o9tt
      authors: Liu, Shao; Luo, Ping; Tang, Mimi; Hu, Qin; Polidoro, Joseph P.; Sun, Shusen; Gong, Zhicheng
        title: Providing pharmacy services during the coronavirus pandemic
         date: 2020-03-28
      journal: Int J Clin Pharm
          DOI: 10.1007/s11096-020-01017-0
          sha: 
       doc_id: 333381
     cord_uid: wz70o9tt

         file: cache/cord-337738-2qck1j1w.json
          key: cord-337738-2qck1j1w
      authors: Martin, Jennifer H.; Clark, Julian; Head, Richard
        title: Buying time: Drug repurposing to treat the host in COVID‐19H
         date: 2020-06-23
      journal: Pharmacol Res Perspect
          DOI: 10.1002/prp2.620
          sha: 
       doc_id: 337738
     cord_uid: 2qck1j1w

         file: cache/cord-323940-ubazgvov.json
          key: cord-323940-ubazgvov
      authors: Cafiero, Concetta; Re, Agnese; Micera, Alessandra; Palmirotta, Raffaele; Monaco, Delio; Romano, Francesca; Fabrizio, Claudia; Di Francia, Raffaele; Cacciamani, Andrea; Surico, Pier Luigi; D’Amato, Gerardo; Pisconti, Salvatore
        title: Pharmacogenomics and Pharmacogenetics: In Silico Prediction of Drug Effects in Treatments for Novel Coronavirus SARS-CoV2 Disease
         date: 2020-10-13
      journal: Pharmgenomics Pers Med
          DOI: 10.2147/pgpm.s270069
          sha: 
       doc_id: 323940
     cord_uid: ubazgvov

         file: cache/cord-330380-wnbyy1gk.json
          key: cord-330380-wnbyy1gk
      authors: Liu, Tingting; Lu, Dong; Zhang, Hao; Zheng, Mingyue; Yang, Huaiyu; Xu, Yechun; Luo, Cheng; Zhu, Weiliang; Yu, Kunqian; Jiang, Hualiang
        title: Applying high-performance computing in drug discovery and molecular simulation
         date: 2016-01-11
      journal: Natl Sci Rev
          DOI: 10.1093/nsr/nww003
          sha: 
       doc_id: 330380
     cord_uid: wnbyy1gk

         file: cache/cord-332038-icyut3xa.json
          key: cord-332038-icyut3xa
      authors: Pillaiyar, Thanigaimalai; Meenakshisundaram, Sangeetha; Manickam, Manoj; Sankaranarayanan, Murugesan
        title: A medicinal chemistry perspective of drug repositioning: Recent advances and challenges in drug discovery
         date: 2020-04-02
      journal: Eur J Med Chem
          DOI: 10.1016/j.ejmech.2020.112275
          sha: 
       doc_id: 332038
     cord_uid: icyut3xa

         file: cache/cord-347579-aqgauumt.json
          key: cord-347579-aqgauumt
      authors: Csete, Joanne
        title: United States drug courts and opioid agonist therapy: Missing the target of overdose reduction
         date: 2020-06-09
      journal: nan
          DOI: 10.1016/j.fsiml.2020.100024
          sha: 
       doc_id: 347579
     cord_uid: aqgauumt

         file: cache/cord-354006-j1y42oxu.json
          key: cord-354006-j1y42oxu
      authors: Ozdemir, Vural; Williams-Jones, Bryn; Glatt, Stephen J; Tsuang, Ming T; Lohr, James B; Reist, Christopher
        title: Shifting emphasis from pharmacogenomics to theragnostics
         date: 2006
      journal: Nat Biotechnol
          DOI: 10.1038/nbt0806-942
          sha: 
       doc_id: 354006
     cord_uid: j1y42oxu

         file: cache/cord-329318-eo8auo1f.json
          key: cord-329318-eo8auo1f
      authors: Gusarov, Sergey; Stoyanov, Stanislav R.
        title: COSMO-RS-Based Descriptors for the Machine Learning-Enabled Screening of Nucleotide Analogue Drugs against SARS-CoV-2
         date: 2020-10-26
      journal: J Phys Chem Lett
          DOI: 10.1021/acs.jpclett.0c02836
          sha: 
       doc_id: 329318
     cord_uid: eo8auo1f

         file: cache/cord-334511-lx9608vy.json
          key: cord-334511-lx9608vy
      authors: Emwas, Abdul-Hamid; Szczepski, Kacper; Poulson, Benjamin Gabriel; Chandra, Kousik; McKay, Ryan T.; Dhahri, Manel; Alahmari, Fatimah; Jaremko, Lukasz; Lachowicz, Joanna Izabela; Jaremko, Mariusz
        title: NMR as a “Gold Standard” Method in Drug Design and Discovery
         date: 2020-10-09
      journal: Molecules
          DOI: 10.3390/molecules25204597
          sha: 
       doc_id: 334511
     cord_uid: lx9608vy

         file: cache/cord-345059-t6hojshj.json
          key: cord-345059-t6hojshj
      authors: Bayoumy, A. B.; de Boer, N. K. H.; Ansari, A. R.; Crouwel, F.; Mulder, C. J. J.
        title: Unrealized potential of drug repositioning in europe during COVID-19 and beyond: a physcian’s perspective
         date: 2020-07-17
      journal: J Pharm Policy Pract
          DOI: 10.1186/s40545-020-00249-9
          sha: 
       doc_id: 345059
     cord_uid: t6hojshj

         file: cache/cord-320172-qw47pf9r.json
          key: cord-320172-qw47pf9r
      authors: Greaves, Peter
        title: VII Digestive System 1
         date: 2000-12-31
      journal: Histopathology of Preclinical Toxicity Studies
          DOI: 10.1016/b978-044450514-9/50007-3
          sha: 
       doc_id: 320172
     cord_uid: qw47pf9r

         file: cache/cord-351222-9bfchw4u.json
          key: cord-351222-9bfchw4u
      authors: Rollinger, Judith M.; Stuppner, Hermann; Langer, Thierry
        title: Virtual screening for the discovery of bioactive natural products
         date: 2008
      journal: Natural Compounds as Drugs Volume I
          DOI: 10.1007/978-3-7643-8117-2_6
          sha: 
       doc_id: 351222
     cord_uid: 9bfchw4u

         file: cache/cord-348102-k0s9j9sz.json
          key: cord-348102-k0s9j9sz
      authors: Silvestris, Nicola; Munafò, Antonio; Brunetti, Oronzo; Burgaletto, Chiara; Scucces, Luisa; Bernardini, Renato
        title: On the Management of Drug Interactions in the Course of Concomitant Treatments for COVID-19 and Antineoplastic Agents
         date: 2020-07-21
      journal: Front Oncol
          DOI: 10.3389/fonc.2020.01340
          sha: 
       doc_id: 348102
     cord_uid: k0s9j9sz

         file: cache/cord-333122-xw8o189s.json
          key: cord-333122-xw8o189s
      authors: Blasiak, A.; Lim, J. J.; Seah, S. G. K.; Kee, T.; Remus, A.; Chye, D. H.; Wong, P. S.; Hooi, L.; Truong, A. T. L.; Le, N.; Chan, C. E. Z.; Desai, R.; Ding, X.; Hanson, B. J.; Chow, E. K.-H.; Ho, D.
        title: IDentif.AI: Artificial Intelligence Pinpoints Remdesivir in Combination with Ritonavir and Lopinavir as an Optimal Regimen Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
         date: 2020-05-08
      journal: nan
          DOI: 10.1101/2020.05.04.20088104
          sha: 
       doc_id: 333122
     cord_uid: xw8o189s

         file: cache/cord-353572-b4mdiont.json
          key: cord-353572-b4mdiont
      authors: Zhou, Yadi; Hou, Yuan; Shen, Jiayu; Huang, Yin; Martin, William; Cheng, Feixiong
        title: Network-based Drug Repurposing for Human Coronavirus
         date: 2020-02-05
      journal: nan
          DOI: 10.1101/2020.02.03.20020263
          sha: 
       doc_id: 353572
     cord_uid: b4mdiont

         file: cache/cord-347986-ds5hm731.json
          key: cord-347986-ds5hm731
      authors: Lee, Paul J.; Krilov, Leonard R.
        title: Developing Infectious Disease Strategies for the Developing World
         date: 2007-01-26
      journal: Annu Rep Med Chem
          DOI: 10.1016/s0065-7743(06)41018-6
          sha: 
       doc_id: 347986
     cord_uid: ds5hm731

         file: cache/cord-342588-berrojmq.json
          key: cord-342588-berrojmq
      authors: Burri, Christian
        title: Sleeping Sickness at the Crossroads
         date: 2020-04-08
      journal: Trop Med Infect Dis
          DOI: 10.3390/tropicalmed5020057
          sha: 
       doc_id: 342588
     cord_uid: berrojmq

         file: cache/cord-350703-vrqltz3s.json
          key: cord-350703-vrqltz3s
      authors: nan
        title: ISAR News
         date: 2016-01-31
      journal: Antiviral Research
          DOI: 10.1016/s0166-3542(15)00286-7
          sha: 
       doc_id: 350703
     cord_uid: vrqltz3s

         file: cache/cord-344934-m0q7rm6z.json
          key: cord-344934-m0q7rm6z
      authors: Mahapatra, Sovesh; Nath, Prathul; Chatterjee, Manisha; Das, Neeladrisingha; Kalita, Deepjyoti; Roy, Partha; Satapathi, Soumitra
        title: Repurposing Therapeutics for COVID-19: Rapid Prediction of Commercially available drugs through Machine Learning and Docking
         date: 2020-04-07
      journal: nan
          DOI: 10.1101/2020.04.05.20054254
          sha: 
       doc_id: 344934
     cord_uid: m0q7rm6z

         file: cache/cord-355971-99mhacqa.json
          key: cord-355971-99mhacqa
      authors: Gougis, Paul; Fenioux, Charlotte; Funck-Brentano, Christian; Veyri, Marianne; Gligorov, Joseph; Solas, Caroline; Spano, Jean-Philippe
        title: Anticancer drugs and COVID-19 antiviral treatments in cancer patients: what can we safely use?
         date: 2020-06-10
      journal: Eur J Cancer
          DOI: 10.1016/j.ejca.2020.05.027
          sha: 
       doc_id: 355971
     cord_uid: 99mhacqa

         file: cache/cord-349682-kpg0vley.json
          key: cord-349682-kpg0vley
      authors: Ojha, Probir Kumar; Kar, Supratik; Krishna, Jillella Gopala; Roy, Kunal; Leszczynski, Jerzy
        title: Therapeutics for COVID-19: from computation to practices—where we are, where we are heading to
         date: 2020-09-02
      journal: Mol Divers
          DOI: 10.1007/s11030-020-10134-x
          sha: 
       doc_id: 349682
     cord_uid: kpg0vley

         file: cache/cord-352579-ndcbmgfj.json
          key: cord-352579-ndcbmgfj
      authors: Takahashi, Takuto; Luzum, Jasmine A.; Nicol, Melanie R.; Jacobson, Pamala A.
        title: Pharmacogenomics of COVID-19 therapies
         date: 2020-08-18
      journal: NPJ Genom Med
          DOI: 10.1038/s41525-020-00143-y
          sha: 
       doc_id: 352579
     cord_uid: ndcbmgfj

         file: cache/cord-349794-mhviub6e.json
          key: cord-349794-mhviub6e
      authors: Le, Brian L.; Andreoletti, Gaia; Oskotsky, Tomiko; Vallejo-Gracia, Albert; Rosales, Romel; Yu, Katharine; Kosti, Idit; Leon, Kristoffer E.; Bunis, Daniel G.; Li, Christine; Kumar, G. Renuka; White, Kris M.; García-Sastre, Adolfo; Ott, Melanie; Sirota, Marina
        title: Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19
         date: 2020-10-23
      journal: bioRxiv
          DOI: 10.1101/2020.10.23.352666
          sha: 
       doc_id: 349794
     cord_uid: mhviub6e

         file: cache/cord-354445-lnvc7mmf.json
          key: cord-354445-lnvc7mmf
      authors: Lichtenstein, David; Alfa, Michelle J.
        title: 4 Cleaning and Disinfecting Gastrointestinal Endoscopy Equipment
         date: 2019-12-31
      journal: Clinical Gastrointestinal Endoscopy
          DOI: 10.1016/b978-0-323-41509-5.00004-9
          sha: 
       doc_id: 354445
     cord_uid: lnvc7mmf

         file: cache/cord-342756-rgm9ffpk.json
          key: cord-342756-rgm9ffpk
      authors: Senger, Mario Roberto; Evangelista, Tereza Cristina Santos; Dantas, Rafael Ferreira; Santana, Marcos Vinicius da Silva; Gonçalves, Luiz Carlos Saramago; de Souza Neto, Lauro Ribeiro; Ferreira, Sabrina Baptista; Silva-Junior, Floriano Paes
        title: COVID-19: molecular targets, drug repurposing and new avenues for drug discovery
         date: 2020-10-02
      journal: Mem Inst Oswaldo Cruz
          DOI: 10.1590/0074-02760200254
          sha: 
       doc_id: 342756
     cord_uid: rgm9ffpk

         file: cache/cord-351517-npcuo1ld.json
          key: cord-351517-npcuo1ld
      authors: Gale, Robert Peter; Lazarus, Hillard M.
        title: Liaisons Dangereuses? new drugs, physicians and the drug industry
         date: 2020-07-01
      journal: Bone Marrow Transplant
          DOI: 10.1038/s41409-020-0988-0
          sha: 
       doc_id: 351517
     cord_uid: npcuo1ld

         file: cache/cord-351185-3y3gou6v.json
          key: cord-351185-3y3gou6v
      authors: Buckles, Thomas C.; Ziemba, Brian P.; Djukovic, Danijel; Falke, Joseph J.
        title: Rapid exposure of macrophages to drugs resolves four classes of effects on the leading edge sensory pseudopod: Non-perturbing, adaptive, disruptive, and activating
         date: 2020-05-29
      journal: PLoS One
          DOI: 10.1371/journal.pone.0233012
          sha: 
       doc_id: 351185
     cord_uid: 3y3gou6v

         file: cache/cord-350571-6tapkjb6.json
          key: cord-350571-6tapkjb6
      authors: nan
        title: 45th ESCP-NSF international symposium on clinical pharmacy: clinical pharmacy tackling inequalities and access to health care. Oslo, Norway, 5–7 October 2016
         date: 2017-01-10
      journal: Int J Clin Pharm
          DOI: 10.1007/s11096-016-0404-4
          sha: 
       doc_id: 350571
     cord_uid: 6tapkjb6

Reading metadata file and updating bibliogrpahics
=== updating bibliographic database
Building study carrel named keyword-drug-cord
parallel: Warning: No more processes: Decreasing number of running jobs to 95.
parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help.
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57142 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56556 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56054 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56139 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56219 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57172 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
parallel: Warning: No more processes: Decreasing number of running jobs to 94.
parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help.
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56876 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56953 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55869 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57582 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
/data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes
parallel: Warning: No more processes: Decreasing number of running jobs to 95.
parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help.
/data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable
/data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable
parallel: Warning: No more processes: Decreasing number of running jobs to 95.
parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help.
parallel: Warning: No more processes: Decreasing number of running jobs to 95.
parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help.
/data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56265 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
/data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable
/data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable
/data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable
/data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable
/data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable
/data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56490 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
/data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56069 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57998 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
/data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57844 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58250 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57164 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58667 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58660 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
/data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes
/data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57807 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 54915 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
/data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55555 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59147 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56392 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60082 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57217 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58187 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58458 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58842 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56384 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59204 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59383 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59377 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58118 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56302 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60293 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58867 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59497 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60125 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60319 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
parallel: Warning: No more processes: Decreasing number of running jobs to 95.
parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help.
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57873 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59714 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59909 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60135 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-006479-iaocovf2
     author: Schreiber, J.
      title: Medikamenteninduzierte parenchymatöse Lungenerkrankungen
       date: 2009-08-01
      pages: 
  extension: .txt
        txt: ./txt/cord-006479-iaocovf2.txt
      cache: ./cache/cord-006479-iaocovf2.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-006479-iaocovf2.txt'
=== file2bib.sh ===
         id: cord-003118-58ta20fg
     author: Van Norman, Gail A.
      title: Expanding Patient Access to Investigational New Drugs: Overview of Intermediate and Widespread Treatment Investigational New Drugs, and Emergency Authorization in Public Health Emergencies
       date: 2018-06-25
      pages: 
  extension: .txt
        txt: ./txt/cord-003118-58ta20fg.txt
      cache: ./cache/cord-003118-58ta20fg.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	2
resourceName	b'cord-003118-58ta20fg.txt'
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64426 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59221 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60157 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60062 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56261 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 54722 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64587 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-001072-pjv3wy80
     author: Hong, Xiaoyun
      title: Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine
       date: 2013-09-04
      pages: 
  extension: .txt
        txt: ./txt/cord-001072-pjv3wy80.txt
      cache: ./cache/cord-001072-pjv3wy80.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	2
resourceName	b'cord-001072-pjv3wy80.txt'
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64729 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-000204-hd12p867
     author: Wu, Han-Chung
      title: Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy
       date: 2010-05-05
      pages: 
  extension: .txt
        txt: ./txt/cord-000204-hd12p867.txt
      cache: ./cache/cord-000204-hd12p867.txt

Content-Encoding	ISO-8859-1
Content-Type	text/plain; charset=ISO-8859-1
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-000204-hd12p867.txt'
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64866 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64235 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64385 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56791 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56151 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66237 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66545 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66701 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66746 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57398 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-263840-1t4ykc01
     author: Altay, Ozlem
      title: Current status of COVID-19 therapies and drug repositioning applications
       date: 2020-06-20
      pages: 
  extension: .txt
        txt: ./txt/cord-263840-1t4ykc01.txt
      cache: ./cache/cord-263840-1t4ykc01.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	2
resourceName	b'cord-263840-1t4ykc01.txt'
=== file2bib.sh ===
         id: cord-001470-hn288o97
     author: Pivette, Mathilde
      title: Drug sales data analysis for outbreak detection of infectious diseases: a systematic literature review
       date: 2014-11-18
      pages: 
  extension: .txt
        txt: ./txt/cord-001470-hn288o97.txt
      cache: ./cache/cord-001470-hn288o97.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-001470-hn288o97.txt'
=== file2bib.sh ===
         id: cord-203232-1nnqx1g9
     author: Canturk, Semih
      title: Machine-Learning Driven Drug Repurposing for COVID-19
       date: 2020-06-25
      pages: 
  extension: .txt
        txt: ./txt/cord-203232-1nnqx1g9.txt
      cache: ./cache/cord-203232-1nnqx1g9.txt

Content-Encoding	ISO-8859-1
Content-Type	text/plain; charset=ISO-8859-1
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-203232-1nnqx1g9.txt'
=== file2bib.sh ===
         id: cord-267979-k70gnrdw
     author: Yıldız-Peköz, Ayca
      title: Advances in Pulmonary Drug Delivery
       date: 2020-09-23
      pages: 
  extension: .txt
        txt: ./txt/cord-267979-k70gnrdw.txt
      cache: ./cache/cord-267979-k70gnrdw.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-267979-k70gnrdw.txt'
=== file2bib.sh ===
         id: cord-033723-jy5fdsp9
     author: Orhobor, Oghenejokpeme I.
      title: Generating Explainable and Effective Data Descriptors Using Relational Learning: Application to Cancer Biology
       date: 2020-09-19
      pages: 
  extension: .txt
        txt: ./txt/cord-033723-jy5fdsp9.txt
      cache: ./cache/cord-033723-jy5fdsp9.txt

Content-Encoding	ISO-8859-1
Content-Type	text/plain; charset=ISO-8859-1
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-033723-jy5fdsp9.txt'
=== file2bib.sh ===
         id: cord-256852-lrz17bdx
     author: Nayyar, Gaurvika M. L.
      title: Responding to the Pandemic of Falsified Medicines
       date: 2015-06-03
      pages: 
  extension: .txt
        txt: ./txt/cord-256852-lrz17bdx.txt
      cache: ./cache/cord-256852-lrz17bdx.txt

Content-Encoding	ISO-8859-1
Content-Type	text/plain; charset=ISO-8859-1
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	2
resourceName	b'cord-256852-lrz17bdx.txt'
=== file2bib.sh ===
         id: cord-001151-mdej7nhj
     author: Kumar De, Amit
      title: Application of an Amine Functionalized Biopolymer in the Colonic Delivery of Glycyrrhizin: A Design and In Vivo Efficacy Study
       date: 2013-05-18
      pages: 
  extension: .txt
        txt: ./txt/cord-001151-mdej7nhj.txt
      cache: ./cache/cord-001151-mdej7nhj.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-001151-mdej7nhj.txt'
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66988 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66765 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66744 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-014875-xhzxhwgo
     author: nan
      title: Book Reviews
       date: 2003
      pages: 
  extension: .txt
        txt: ./txt/cord-014875-xhzxhwgo.txt
      cache: ./cache/cord-014875-xhzxhwgo.txt

Content-Encoding	ISO-8859-1
Content-Type	text/plain; charset=ISO-8859-1
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	2
resourceName	b'cord-014875-xhzxhwgo.txt'
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66903 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66963 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-009763-44fexcpt
     author: Reddy, Mynampati Akshitha
      title: Internet-of-Things-Enabled Dual-Channel Iontophoretic Drug Delivery System for Elderly Patient Medication Management
       date: 2020-03-01
      pages: 
  extension: .txt
        txt: ./txt/cord-009763-44fexcpt.txt
      cache: ./cache/cord-009763-44fexcpt.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-009763-44fexcpt.txt'
=== file2bib.sh ===
         id: cord-261311-j6bmgmhz
     author: Parreiras Martins, Maria Auxiliadora
      title: Preparedness of pharmacists to respond to the emergency of the COVID-19 pandemic in Brazil: a comprehensive overview
       date: 2020-07-31
      pages: 
  extension: .txt
        txt: ./txt/cord-261311-j6bmgmhz.txt
      cache: ./cache/cord-261311-j6bmgmhz.txt

Content-Encoding	ISO-8859-1
Content-Type	text/plain; charset=ISO-8859-1
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-261311-j6bmgmhz.txt'
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67369 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67943 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67214 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67622 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-001244-qdld7hdc
     author: Fan, Yue-Nong
      title: iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking
       date: 2014-03-19
      pages: 
  extension: .txt
        txt: ./txt/cord-001244-qdld7hdc.txt
      cache: ./cache/cord-001244-qdld7hdc.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-001244-qdld7hdc.txt'
=== file2bib.sh ===
         id: cord-232446-vvb2ffhv
     author: Mongia, Aanchal
      title: A computational approach to aid clinicians in selecting anti-viral drugs for COVID-19 trials
       date: 2020-07-03
      pages: 
  extension: .txt
        txt: ./txt/cord-232446-vvb2ffhv.txt
      cache: ./cache/cord-232446-vvb2ffhv.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-232446-vvb2ffhv.txt'
=== file2bib.sh ===
         id: cord-267608-0odu8lus
     author: Chen, Daohong
      title: Innovative highlights of clinical drug trial design
       date: 2020-06-03
      pages: 
  extension: .txt
        txt: ./txt/cord-267608-0odu8lus.txt
      cache: ./cache/cord-267608-0odu8lus.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-267608-0odu8lus.txt'
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67942 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67620 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-203191-7ftg6bfx
     author: Guo, Kai
      title: Identification of Repurposal Drugs and Adverse Drug Reactions for Various Courses of Coronavirus Disease 2019 (COVID-19) Based on Single-cell RNA Sequencing Data
       date: 2020-05-16
      pages: 
  extension: .txt
        txt: ./txt/cord-203191-7ftg6bfx.txt
      cache: ./cache/cord-203191-7ftg6bfx.txt

Content-Encoding	ISO-8859-1
Content-Type	text/plain; charset=ISO-8859-1
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-203191-7ftg6bfx.txt'
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66571 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-275772-pmf6stua
     author: Jourdan, Jean‐Pierre
      title: Drug repositioning: a brief overview
       date: 2020-04-17
      pages: 
  extension: .txt
        txt: ./txt/cord-275772-pmf6stua.txt
      cache: ./cache/cord-275772-pmf6stua.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-275772-pmf6stua.txt'
=== file2bib.sh ===
         id: cord-102823-zult69f2
     author: Nguyen, Thin
      title: GraphDTA: Predicting drug–target binding affinity with graph neural networks
       date: 2020-10-02
      pages: 
  extension: .txt
        txt: ./txt/cord-102823-zult69f2.txt
      cache: ./cache/cord-102823-zult69f2.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-102823-zult69f2.txt'
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68234 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68062 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68248 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68403 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-000182-ni6iyzdn
     author: He, Zhisong
      title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features
       date: 2010-03-11
      pages: 
  extension: .txt
        txt: ./txt/cord-000182-ni6iyzdn.txt
      cache: ./cache/cord-000182-ni6iyzdn.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-000182-ni6iyzdn.txt'
=== file2bib.sh ===
         id: cord-104431-3rblzyry
     author: Hill, Andrew
      title: Minimum costs to manufacture new treatments for COVID-19
       date: 2020-04-30
      pages: 
  extension: .txt
        txt: ./txt/cord-104431-3rblzyry.txt
      cache: ./cache/cord-104431-3rblzyry.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-104431-3rblzyry.txt'
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68657 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66529 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68820 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-299225-exbdg3x9
     author: Guarnieri, Michael
      title: A Long-Term Study of a Lipid-Buprenorphine Implant in Rats
       date: 2018-07-09
      pages: 
  extension: .txt
        txt: ./txt/cord-299225-exbdg3x9.txt
      cache: ./cache/cord-299225-exbdg3x9.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-299225-exbdg3x9.txt'
=== file2bib.sh ===
         id: cord-007511-5d5authn
     author: Gil, JP
      title: CYP2C8 and antimalaria drug efficacy
       date: 2007-02-07
      pages: 
  extension: .txt
        txt: ./txt/cord-007511-5d5authn.txt
      cache: ./cache/cord-007511-5d5authn.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-007511-5d5authn.txt'
=== file2bib.sh ===
         id: cord-016309-6mw8okmt
     author: Bule, Mohammed
      title: Antivirals: Past, Present and Future
       date: 2019-06-06
      pages: 
  extension: .txt
        txt: ./txt/cord-016309-6mw8okmt.txt
      cache: ./cache/cord-016309-6mw8okmt.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-016309-6mw8okmt.txt'
=== file2bib.sh ===
         id: cord-024833-e6vcf4un
     author: nan
      title: Forum
       date: 2019-12-19
      pages: 
  extension: .txt
        txt: ./txt/cord-024833-e6vcf4un.txt
      cache: ./cache/cord-024833-e6vcf4un.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	2
resourceName	b'cord-024833-e6vcf4un.txt'
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68663 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-016283-b6yywn9f
     author: Hasan, Ashfaq
      title: Clinical Aspects and Principles of Management of Tuberculosis
       date: 2019-08-07
      pages: 
  extension: .txt
        txt: ./txt/cord-016283-b6yywn9f.txt
      cache: ./cache/cord-016283-b6yywn9f.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-016283-b6yywn9f.txt'
=== file2bib.sh ===
         id: cord-214795-8jweuq50
     author: Mongia, Aanchal
      title: DeepVir -- Graphical Deep Matrix Factorization for"In Silico"Antiviral Repositioning: Application to COVID-19
       date: 2020-09-22
      pages: 
  extension: .txt
        txt: ./txt/cord-214795-8jweuq50.txt
      cache: ./cache/cord-214795-8jweuq50.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-214795-8jweuq50.txt'
=== file2bib.sh ===
         id: cord-256118-gxhhwqdd
     author: Abadie, R.
      title: “Caballo”: risk environments, drug sharing and the emergence of a hepatitis C virus epidemic among people who inject drugs in Puerto Rico
       date: 2020-10-23
      pages: 
  extension: .txt
        txt: ./txt/cord-256118-gxhhwqdd.txt
      cache: ./cache/cord-256118-gxhhwqdd.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-256118-gxhhwqdd.txt'
=== file2bib.sh ===
         id: cord-253115-ekgdsv4f
     author: Mehta, Meenu
      title: Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases
       date: 2019-08-01
      pages: 
  extension: .txt
        txt: ./txt/cord-253115-ekgdsv4f.txt
      cache: ./cache/cord-253115-ekgdsv4f.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-253115-ekgdsv4f.txt'
=== file2bib.sh ===
         id: cord-302018-3rlya16w
     author: Castells, Mariana C.
      title: Drug allergy labeling and delabeling in the coronavirus disease 2019 era: What is important and what do we need to know
       date: 2020-05-22
      pages: 
  extension: .txt
        txt: ./txt/cord-302018-3rlya16w.txt
      cache: ./cache/cord-302018-3rlya16w.txt

Content-Encoding	ISO-8859-1
Content-Type	text/plain; charset=ISO-8859-1
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-302018-3rlya16w.txt'
=== file2bib.sh ===
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70306 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69800 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70021 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70373 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68959 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69282 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58319 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70429 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69871 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-262442-kjgpriow
     author: Scalia, Santo
      title: Quercetin solid lipid microparticles: A flavonoid for inhalation lung delivery
       date: 2013-05-13
      pages: 
  extension: .txt
        txt: ./txt/cord-262442-kjgpriow.txt
      cache: ./cache/cord-262442-kjgpriow.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-262442-kjgpriow.txt'
=== file2bib.sh ===
         id: cord-257496-mirh80gn
     author: Hickey, Anthony J.
      title: Emerging trends in inhaled drug delivery
       date: 2020-07-12
      pages: 
  extension: .txt
        txt: ./txt/cord-257496-mirh80gn.txt
      cache: ./cache/cord-257496-mirh80gn.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-257496-mirh80gn.txt'
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66977 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70309 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70685 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70759 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-258614-7unadw41
     author: Ogidigo, Joyce Oloaigbe
      title: Natural phyto, compounds as possible noncovalent inhibitors against SARS-CoV2 protease: computational approach
       date: 2020-10-25
      pages: 
  extension: .txt
        txt: ./txt/cord-258614-7unadw41.txt
      cache: ./cache/cord-258614-7unadw41.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-258614-7unadw41.txt'
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71176 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70884 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70639 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71402 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69915 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-308994-4nljzm8a
     author: Tang, Zhongmin
      title: Insights from nanotechnology in COVID-19 treatment
       date: 2020-11-04
      pages: 
  extension: .txt
        txt: ./txt/cord-308994-4nljzm8a.txt
      cache: ./cache/cord-308994-4nljzm8a.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	2
resourceName	b'cord-308994-4nljzm8a.txt'
=== file2bib.sh ===
         id: cord-285603-f4572w5m
     author: Ortega, Joseph T.
      title: Class A G Protein-Coupled Receptor Antagonist Famotidine as a Therapeutic Alternative against SARS-CoV2: An In Silico Analysis
       date: 2020-06-24
      pages: 
  extension: .txt
        txt: ./txt/cord-285603-f4572w5m.txt
      cache: ./cache/cord-285603-f4572w5m.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-285603-f4572w5m.txt'
=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70378 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-309871-y17puao2
     author: Scherrmann, JM.
      title: Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy
       date: 2020-06-12
      pages: 
  extension: .txt
        txt: ./txt/cord-309871-y17puao2.txt
      cache: ./cache/cord-309871-y17puao2.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-309871-y17puao2.txt'
=== file2bib.sh ===
         id: cord-325315-m3do6t1j
     author: Rossi, Carlo Maria
      title: A case report of toxic epidermal necrolysis (TEN) in a patient with COVID-19 treated with hydroxychloroquine: are these two partners in crime?
       date: 2020-10-06
      pages: 
  extension: .txt
        txt: ./txt/cord-325315-m3do6t1j.txt
      cache: ./cache/cord-325315-m3do6t1j.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	2
resourceName	b'cord-325315-m3do6t1j.txt'
=== file2bib.sh ===
         id: cord-017583-72mbsib7
     author: Devarajan, Padma V.
      title: Infectious Diseases: Need for Targeted Drug Delivery
       date: 2014-09-01
      pages: 
  extension: .txt
        txt: ./txt/cord-017583-72mbsib7.txt
      cache: ./cache/cord-017583-72mbsib7.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-017583-72mbsib7.txt'
=== file2bib.sh ===
         id: cord-299400-j18pj11d
     author: Norinder, Ulf
      title: Existing highly accumulating lysosomotropic drugs with potential for repurposing to target COVID-19
       date: 2020-07-30
      pages: 
  extension: .txt
        txt: ./txt/cord-299400-j18pj11d.txt
      cache: ./cache/cord-299400-j18pj11d.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-299400-j18pj11d.txt'
=== file2bib.sh ===
         id: cord-324660-w81jgw7p
     author: Guharoy, Roy
      title: Medication Shortages: A Matter of National Security—Time for Action
       date: 2020-08-01
      pages: 
  extension: .txt
        txt: ./txt/cord-324660-w81jgw7p.txt
      cache: ./cache/cord-324660-w81jgw7p.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	2
resourceName	b'cord-324660-w81jgw7p.txt'
=== file2bib.sh ===
         id: cord-348245-pf5mlzrw
     author: Moura-Neto, José A.
      title: Position statement from the Brazilian Society of Nephrology regarding chloroquine and hydroxychloroquine drug dose adjustment according to renal function
       date: 2020-08-26
      pages: 
  extension: .txt
        txt: ./txt/cord-348245-pf5mlzrw.txt
      cache: ./cache/cord-348245-pf5mlzrw.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	2
resourceName	b'cord-348245-pf5mlzrw.txt'
=== file2bib.sh ===
         id: cord-316029-z708c3ex
     author: Brunsdon, Priya
      title: Clinical Pharmacology Considerations for Developing Small‐Molecule Treatments for COVID‐19
       date: 2020-07-12
      pages: 
  extension: .txt
        txt: ./txt/cord-316029-z708c3ex.txt
      cache: ./cache/cord-316029-z708c3ex.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	2
resourceName	b'cord-316029-z708c3ex.txt'
=== file2bib.sh ===
         id: cord-268088-y4vg7frb
     author: Montané, Xavier
      title: Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy
       date: 2020-07-23
      pages: 
  extension: .txt
        txt: ./txt/cord-268088-y4vg7frb.txt
      cache: ./cache/cord-268088-y4vg7frb.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-268088-y4vg7frb.txt'
=== file2bib.sh ===
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes
         id: cord-299911-v95pf3eg
     author: El-Ghiaty, Mahmoud A.
      title: Cytochrome P450-mediated drug interactions in COVID-19 patients: current findings and possible mechanisms
       date: 2020-06-26
      pages: 
  extension: .txt
        txt: ./txt/cord-299911-v95pf3eg.txt
      cache: ./cache/cord-299911-v95pf3eg.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-299911-v95pf3eg.txt'
=== file2bib.sh ===
         id: cord-273716-vv3pyft4
     author: Khosravi-Darani, Kianoush
      title: The role of high-resolution imaging in the evaluation of nanosystems for bioactive encapsulation and targeted nanotherapy
       date: 2007-07-03
      pages: 
  extension: .txt
        txt: ./txt/cord-273716-vv3pyft4.txt
      cache: ./cache/cord-273716-vv3pyft4.txt

Content-Encoding	ISO-8859-1
Content-Type	text/plain; charset=ISO-8859-1
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-273716-vv3pyft4.txt'
=== file2bib.sh ===
         id: cord-311730-189vax2m
     author: Becker, Richard C.
      title: Covid-19 treatment update: follow the scientific evidence
       date: 2020-04-27
      pages: 
  extension: .txt
        txt: ./txt/cord-311730-189vax2m.txt
      cache: ./cache/cord-311730-189vax2m.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-311730-189vax2m.txt'
=== file2bib.sh ===
         id: cord-292041-a65kfw80
     author: Orienti, Isabella
      title: Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment in COVID-19
       date: 2020-05-27
      pages: 
  extension: .txt
        txt: ./txt/cord-292041-a65kfw80.txt
      cache: ./cache/cord-292041-a65kfw80.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-292041-a65kfw80.txt'
=== file2bib.sh ===
         id: cord-289321-ahl46ql9
     author: van Buuren, Nicholas
      title: Transmission genetics of drug-resistant hepatitis C virus
       date: 2018-03-28
      pages: 
  extension: .txt
        txt: ./txt/cord-289321-ahl46ql9.txt
      cache: ./cache/cord-289321-ahl46ql9.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	4
resourceName	b'cord-289321-ahl46ql9.txt'
=== file2bib.sh ===
         id: cord-297010-imciixde
     author: Babayeva, Mariana
      title: Repurposing Drugs for COVID-19: Pharmacokinetics and Pharmacogenomics of Chloroquine and Hydroxychloroquine
       date: 2020-10-23
      pages: 
  extension: .txt
        txt: ./txt/cord-297010-imciixde.txt
      cache: ./cache/cord-297010-imciixde.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
X-Parsed-By	['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser']
X-TIKA:content_handler	ToTextContentHandler
X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	2
resourceName	b'cord-297010-imciixde.txt'
=== file2bib.sh ===
         id: cord-314827-yqr7110e
     author: Attia, Yasmeen M.
      title: Successful stories of drug repurposing for cancer therapy in hepatocellular carcinoma
       date: 2020-09-04
      pages: 
  extension: .txt
        txt: ./txt/cord-314827-yqr7110e.txt
      cache: ./cache/cord-314827-yqr7110e.txt

Content-Encoding	UTF-8
Content-Type	text/plain; charset=UTF-8
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X-TIKA:embedded_depth	0
X-TIKA:parse_time_millis	3
resourceName	b'cord-314827-yqr7110e.txt'
=== file2bib.sh ===
         id: cord-318048-6nvi63rq
     author: Arshad, Usman
      title: Prioritisation of Anti‐SARS‐Cov‐2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics
       date: 2020-05-21
      pages: 
  extension: .txt
        txt: ./txt/cord-318048-6nvi63rq.txt
      cache: ./cache/cord-318048-6nvi63rq.txt

Content-Encoding	UTF-8
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X-TIKA:embedded_depth	0
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resourceName	b'cord-318048-6nvi63rq.txt'
=== file2bib.sh ===
         id: cord-334881-x9nxxled
     author: Di Lorenzo, Giuseppe
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=== file2bib.sh ===
         id: cord-274474-u2fdicgz
     author: Majumder, Joydeb
      title: Targeted Nanotherapeutics for Respiratory Diseases: Cancer, Fibrosis, and Coronavirus
       date: 2020-10-13
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=== file2bib.sh ===
         id: cord-355971-99mhacqa
     author: Gougis, Paul
      title: Anticancer drugs and COVID-19 antiviral treatments in cancer patients: what can we safely use?
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=== file2bib.sh ===
         id: cord-353524-3w970ycx
     author: Dömling, Alexander
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=== file2bib.sh ===
         id: cord-288026-vcp8o5xn
     author: DeStefano, Vincent
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=== file2bib.sh ===
         id: cord-326922-bajpr5a2
     author: Watson, C. James
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=== file2bib.sh ===
         id: cord-317993-012hx4kc
     author: Movia, Dania
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=== file2bib.sh ===
         id: cord-321741-aq76s37x
     author: Andersen, Petter I.
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=== file2bib.sh ===
         id: cord-321657-2s1npse5
     author: Du, Sean Quan
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=== file2bib.sh ===
         id: cord-354180-6esn3t2b
     author: Tyndall, Mark
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=== file2bib.sh ===
         id: cord-329318-eo8auo1f
     author: Gusarov, Sergey
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=== file2bib.sh ===
         id: cord-347986-ds5hm731
     author: Lee, Paul J.
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=== file2bib.sh ===
         id: cord-334170-85x5vmyi
     author: Masoudi-Sobhanzadeh, Yosef
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=== file2bib.sh ===
         id: cord-303555-mwu72q7w
     author: Dent, Paul
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=== file2bib.sh ===
         id: cord-304506-6el2ryl8
     author: Watkins, Laura C.
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=== file2bib.sh ===
         id: cord-298369-66ifwtlp
     author: Smith, Sherri A.
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=== file2bib.sh ===
         id: cord-347579-aqgauumt
     author: Csete, Joanne
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=== file2bib.sh ===
         id: cord-349794-mhviub6e
     author: Le, Brian L.
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=== file2bib.sh ===
         id: cord-018595-x3tleomb
     author: Dodiuk-Gad, Roni P.
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=== file2bib.sh ===
         id: cord-322885-ob5euspo
     author: Durdagi, Serdar
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=== file2bib.sh ===
         id: cord-353572-b4mdiont
     author: Zhou, Yadi
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=== file2bib.sh ===
         id: cord-316792-89f8g0m8
     author: Herzig, Volker
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=== file2bib.sh ===
         id: cord-330380-wnbyy1gk
     author: Liu, Tingting
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=== file2bib.sh ===
         id: cord-315918-12rbbe8c
     author: Mukherjee, Pulok K.
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=== file2bib.sh ===
         id: cord-351185-3y3gou6v
     author: Buckles, Thomas C.
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=== file2bib.sh ===
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes
         id: cord-322915-zrjx31ev
     author: Demain, Arnold L
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=== file2bib.sh ===
         id: cord-298033-kzdp9edn
     author: Domingo, Esteban
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       date: 2019-11-08
      pages: 
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=== file2bib.sh ===
         id: cord-354445-lnvc7mmf
     author: Lichtenstein, David
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       date: 2019-12-31
      pages: 
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=== file2bib.sh ===
         id: cord-336554-n8n5ii5k
     author: Singh, Thakur Uttam
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=== file2bib.sh ===
         id: cord-007798-9ht7cqhu
     author: Smith, Silas W.
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=== file2bib.sh ===
         id: cord-032561-x3qbqy69
     author: Liu, Gengqi
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=== file2bib.sh ===
         id: cord-342756-rgm9ffpk
     author: Senger, Mario Roberto
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=== file2bib.sh ===
         id: cord-265848-afkeuwup
     author: nan
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=== file2bib.sh ===
         id: cord-334511-lx9608vy
     author: Emwas, Abdul-Hamid
      title: NMR as a “Gold Standard” Method in Drug Design and Discovery
       date: 2020-10-09
      pages: 
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=== file2bib.sh ===
         id: cord-284648-yznlgzir
     author: Varanko, Anastasia
      title: Recent trends in protein and peptide-based biomaterials for advanced drug delivery
       date: 2020-08-29
      pages: 
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=== file2bib.sh ===
         id: cord-275828-c6d6nk7x
     author: Mikasa, Keiichi
      title: JAID/JSC Guidelines for the Treatment of Respiratory Infectious Diseases: The Japanese Association for Infectious Diseases/Japanese Society of Chemotherapy – The JAID/JSC Guide to Clinical Management of Infectious Disease/Guideline-preparing Committee Respiratory Infectious Disease WG
       date: 2016-07-31
      pages: 
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=== file2bib.sh ===
         id: cord-023509-tvqpv6fp
     author: Corrin, Bryan
      title: Occupational, environmental and iatrogenic lung disease
       date: 2011-03-02
      pages: 
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=== file2bib.sh ===
OMP: Error #34: System unable to allocate necessary resources for OMP thread:
OMP: System error #11: Resource temporarily unavailable
OMP: Hint Try decreasing the value of OMP_NUM_THREADS.
/data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55456 Aborted                 $FILE2BIB "$FILE" > "$OUTPUT"
=== file2bib.sh ===
         id: cord-015334-8p124rwp
     author: nan
      title: ESCP 36th European Symposium on Clinical Pharmacy ‘Implementing Clinical Pharmacy in Community and Hospital Settings: Sharing the Experience’, Istanbul, Turkey 25–27 October 2007; Abstracts
       date: 2008-06-11
      pages: 
  extension: .txt
        txt: ./txt/cord-015334-8p124rwp.txt
      cache: ./cache/cord-015334-8p124rwp.txt

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=== file2bib.sh ===
         id: cord-320172-qw47pf9r
     author: Greaves, Peter
      title: VII Digestive System 1
       date: 2000-12-31
      pages: 
  extension: .txt
        txt: ./txt/cord-320172-qw47pf9r.txt
      cache: ./cache/cord-320172-qw47pf9r.txt

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=== file2bib.sh ===
         id: cord-014687-0am4l5ms
     author: nan
      title: SPR 2012
       date: 2012-03-29
      pages: 
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      cache: ./cache/cord-014687-0am4l5ms.txt

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=== file2bib.sh ===
         id: cord-350571-6tapkjb6
     author: nan
      title: 45th ESCP-NSF international symposium on clinical pharmacy: clinical pharmacy tackling inequalities and access to health care. Oslo, Norway, 5–7 October 2016
       date: 2017-01-10
      pages: 
  extension: .txt
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=== file2bib.sh ===
         id: cord-006229-7yoilsho
     author: nan
      title: Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH)
       date: 2016-02-06
      pages: 
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Que is empty; done
keyword-drug-cord
=== reduce.pl bib ===
         id = cord-001072-pjv3wy80
     author = Hong, Xiaoyun
      title = Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine
       date = 2013-09-04
      pages = 
  extension = .txt
       mime = text/plain
      words = 4118
  sentences = 196
     flesch = 41
    summary = Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. 13, 14 Microneedles are mostly applied for the transdermal delivery of drugs and vaccines that may require long exposure, among which the dissolving and biodegradable microneedle technologies are most commonly seen. Microneedle technologies for sustained drug delivery has long been recognized as a highly immune reactive tissue containing an abundance of antigen-presenting cells and immunocompetent cells, especially within the epidermal and dermal skin layers. 36 DeMuth et al 37 reported an approach for rapid implantation of vaccine-loaded polymer films carrying DNA, immune-stimulatory RNA, and biodegradable polycations using microneedles coated with releasable polyelectrolyte multilayers that promoted local transfection and controlled the persistence of DNA and adjuvants in the skin from days to weeks, with kinetics determined by the film composition. 29, 35 Altogether, dissolving and biodegradable microneedle technologies have a bright future for transdermal sustained delivery of drug and vaccine, and require further studies.
      cache = ./cache/cord-001072-pjv3wy80.txt
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=== reduce.pl bib ===
         id = cord-006479-iaocovf2
     author = Schreiber, J.
      title = Medikamenteninduzierte parenchymatöse Lungenerkrankungen
       date = 2009-08-01
      pages = 
  extension = .txt
       mime = text/plain
      words = 1825
  sentences = 214
     flesch = 34
    summary = In diesem Beitrag wird eine Übersicht über medikamentös induzierte Erkrankungen des Lungenparenchyms, aber auch Reaktionsmuster wie das nichtkardiogene Lungenödem, die diffuse alveoläre Hämorrhagie, das medikamenteninduzierte ARDS ("acute respiratory distress syndrome") und eosinophile Lungenparenchymerkrankungen gegeben. So ist beispielsweise die früher häufige Nitrofurantoinlunge heute selten geworden, eine früher ebenfalls häufige Goldlunge als Folge einer Therapie einer rheumatoiden Arthritis mit Goldpräparaten dürfte heute nicht mehr auftreten. Eine Schädigung des Lungenparenchyms durch Medikamente manifestiert sich meist, jedoch nicht immer in Form einer Alveolitis oder Lungenfibrose und kann durch eine Vielzahl von Arzneimitteln induziert werden (. Interstitial lung disease · Hemorrhage · Allergic reaction · Toxicity · Drug cessation Bei begründetem Verdacht ist eine Medikamentenkarenz und in Abhängigkeit vom Schweregrad der Reaktion eine Therapie mit Glukokortikosteroiden indiziert. Die pulmonale Toxizität von Zytostatika wird in eine früh, während der Therapie einsetzende ("early onset") Form (.
      cache = ./cache/cord-006479-iaocovf2.txt
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=== reduce.pl bib ===
         id = cord-001244-qdld7hdc
     author = Fan, Yue-Nong
      title = iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking
       date = 2014-03-19
      pages = 
  extension = .txt
       mime = text/plain
      words = 6502
  sentences = 339
     flesch = 46
    summary = In the predictor, the drug compound concerned was formulated by a 256-D (dimensional) vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine) algorithm. [59] did not provide a publicly accessible web-server for their method, and hence its practical application value is quite limited, particularly for the broad experimental scientists; (b) The prediction quality can be further enhanced by incorporating some key features into the formulation of NR-drug (nuclear receptor and drug) samples via the general form of pseudo amino acid composition [60] . Prediction of G-protein-coupled receptor classes based on the concept of Chou's pseudo amino acid composition: An approach from discrete wavelet transform
      cache = ./cache/cord-001244-qdld7hdc.txt
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=== reduce.pl bib ===
         id = cord-014875-xhzxhwgo
     author = nan
      title = Book Reviews
       date = 2003
      pages = 
  extension = .txt
       mime = text/plain
      words = 7144
  sentences = 338
     flesch = 46
    summary = The last chapter in the second focused area is by Pumpens and Grens, who provide an in-depth discussion of the use of viral vectors for delivering a desirable gene into target cells for protein production. The chapters don't cover material in great depth (and if they did, this book will be many times larger) but they provide enough information to cover what someone new to the area would need to know to get started. As described above, this book does not intend to summarize transporters related to drugs rather tried to introduce many technologies to be used in future studies for molecular cloning, structure, functionality, regulation, and sorting in various point of views by using typical experimental results on physiologically important transporter molecules. Each chapter provides a polymer-based step-bystep description of not only basic information including various classification, application, and structure-property relationships, but also very practical descriptions of synthetic and analytic techniques that are believed to be good references in research laboratories.
      cache = ./cache/cord-014875-xhzxhwgo.txt
       txt  = ./txt/cord-014875-xhzxhwgo.txt
=== reduce.pl bib ===
         id = cord-001470-hn288o97
     author = Pivette, Mathilde
      title = Drug sales data analysis for outbreak detection of infectious diseases: a systematic literature review
       date = 2014-11-18
      pages = 
  extension = .txt
       mime = text/plain
      words = 4423
  sentences = 260
     flesch = 50
    summary = CONCLUSIONS: Drug sales data analyses appear to be a useful tool for surveillance of gastrointestinal and respiratory disease, and OTC drugs have the potential for early outbreak detection. Published articles were searched for on electronic databases (Pubmed, Embase, Scopus, LILACS, African Index Medicus, Cochrane Library), using combinations of the following key words: ("surveillance" OR outbreak detection OR warning system) AND (overthe-counter OR "prescription drugs" OR pharmacy OR (pharmaceutical OR drug OR medication) sales). Articles excluded based on fulltext review (no drug sales data, no infectious disease, no outbreak detection) N= 85 Figure 1 Flow chart of study selection process in a systematic review of drug sales data analysis for syndromic surveillance of infectious diseases. Nineteen of the 27 studies were descriptive retrospective studies assessing the strength of the correlation between drug sales and reference surveillance data of the corresponding disease or evaluating outbreak-detection performance [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] .
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=== reduce.pl bib ===
=== reduce.pl bib ===
         id = cord-001151-mdej7nhj
     author = Kumar De, Amit
      title = Application of an Amine Functionalized Biopolymer in the Colonic Delivery of Glycyrrhizin: A Design and In Vivo Efficacy Study
       date = 2013-05-18
      pages = 
  extension = .txt
       mime = text/plain
      words = 5109
  sentences = 271
     flesch = 51
    summary = The entrapment efficiency and in vitro drug release were studied in simulated gastric, intestinal, and colonic fluids containing rat cecal contents. The in vitro drug release study was carried out in simulated gastric fluid of pH 1.2, simulated intestinal fluid of pH 6.8, and simulated colonic fluid of pH 7.4 containing rat cecal contents under anaerobic conditions. The drug release studies from the microparticles were carried out in the simulated gastric fluid of pH 1.2, simulated intestinal fluid of pH 6.8, and simulated colonic fluid of pH 7.4 containing rat cecal contents [34, 35] . In the simulated colonic fluid containing rat cecal contents, the drug release was a bit more augmented with an initial burst release common for each of the designed The results predict the drug-polymer ratio to be the key factor for controlling the release.
      cache = ./cache/cord-001151-mdej7nhj.txt
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=== reduce.pl bib ===
         id = cord-016309-6mw8okmt
     author = Bule, Mohammed
      title = Antivirals: Past, Present and Future
       date = 2019-06-06
      pages = 
  extension = .txt
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      words = 8200
  sentences = 405
     flesch = 36
    summary = Those included usage restricted to a single virus and specific animal species, problems with high spectrum activity and low cytotoxicity, high costs of development of new chemical compounds and absence of rapid diagnostic techniques allowing prompt use of a specific antiviral agent in the course of an acute infection (Rollinson 1992a, b) . Nevertheless, several licensed human antiviral agents are being used with cascade principle for treatment of animal diseases (e.g. acyclovir, idoxuridine and trifluridine against feline herpesvirus-1 ocular infection in cats) (Thiry et al. The discovery of PAA (Fig. 22.4) as an antiviral drug gave rise to intense research on its biological activities, which demonstrated PAA and its derivatives' ability to inhibit the replication of a number of viruses such as immunodeficiency, hepatitis and herpes viruses. To conclude with, equine herpesvirus type 1 (EHV-1) infection causes outbreak of respiratory and various neurological diseases in horses, against which acyclovir and valacyclovir are the most common drugs, but also IFN targeting IFNGR complex as a key mediator of virus-specific cellular immunity (Poelaert et al.
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=== reduce.pl bib ===
         id = cord-003118-58ta20fg
     author = Van Norman, Gail A.
      title = Expanding Patient Access to Investigational New Drugs: Overview of Intermediate and Widespread Treatment Investigational New Drugs, and Emergency Authorization in Public Health Emergencies
       date = 2018-06-25
      pages = 
  extension = .txt
       mime = text/plain
      words = 2205
  sentences = 109
     flesch = 46
    summary = Individual patients with life-threatening or severely debilitating diseases can petition the U.S. Food and Drug Administration (FDA) through their physicians to have expanded access (EA) to drugs that are in clinical trials but have not reached full FDA approval (the "single-patient" investigational new drug [IND] application). Spurred by patient advocacy during the early days of the acquired immunodeficiency syndrome (AIDS) epidemic in the late 1980s, and facilitated by subsequent legislative efforts over the next 20 years, regulatory initiatives permit the FDA to release drugs for use in individual patients through expanded access (EA) INDs (4, 5) , in many cases allowing emergency treatment with nonapproved drugs within hours of application, and nonemergency treatment within an average of 4 days (6) . Releasing investigational new drugs to individual patients who are facing certain death or disability seems to be a relatively uncomplicated decision, but allowing EA to entire groups of patients for treatment with an investigational new drug presents more complex regulatory, logistical, and ethical challenges for scientists, commercial entities, and the FDA.
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=== reduce.pl bib ===
=== reduce.pl bib ===
         id = cord-000204-hd12p867
     author = Wu, Han-Chung
      title = Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy
       date = 2010-05-05
      pages = 
  extension = .txt
       mime = text/plain
      words = 4433
  sentences = 217
     flesch = 32
    summary = title: Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. This article reviews the current research in developing liposomal drug delivery systems that use peptide ligands to target blood vessels in solid tumors. One peptide-conjugated liposome can deliver over ten thousand anticancer drug molecules directly into target tumor cells efficiently and effectively. In the future, combining ligands that specifically bind to cancer cells (including cancer stem cells) and tumor blood vessels with multifunctional liposomal drug delivery systems may help improve the effectiveness of cancer treatment and minimize the side effects traditionally associated with chemotherapy. The potential use of ligand-conjugated liposome-encapsulated drugs to target tumor cells and vasculature is very promising.
      cache = ./cache/cord-000204-hd12p867.txt
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=== reduce.pl bib ===
         id = cord-009763-44fexcpt
     author = Reddy, Mynampati Akshitha
      title = Internet-of-Things-Enabled Dual-Channel Iontophoretic Drug Delivery System for Elderly Patient Medication Management
       date = 2020-03-01
      pages = 
  extension = .txt
       mime = text/plain
      words = 5226
  sentences = 331
     flesch = 55
    summary = In this study, the development of an iontophoretic drug delivery device that could be controlled using a mobile is described. A mobile app was developed to control the two-channel iontophoretic device and to monitor the loose lead of the active and the passive patches. Taking the cue from the above discussion, a smartphone-based remote-controlled iontophoretic drug delivery device has been developed in this study. Eagle PCB design software was used for the designing of the PCB for the developed circuit of the iontophoretic device with loose-lead monitoring capability (see Fig. S2 available in the Supplemental Materials on the ASME Digital Collection). While doing the drug release study in the active mode, the iontophoretic device was put on using the developed mobile app. The components of the proposed device, namely, the signal generator, the iontophoretic setup, the loose-lead monitoring system, and the Android app based wireless control system, were tested for their proper functionality.
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=== reduce.pl bib ===
         id = cord-007798-9ht7cqhu
     author = Smith, Silas W.
      title = Drugs and pharmaceuticals: management of intoxication and antidotes
       date = 2010-02-25
      pages = 
  extension = .txt
       mime = text/plain
      words = 22555
  sentences = 1371
     flesch = 34
    summary = In the context of analgesic, anti-inflammatory, anticholinergic, anticonvulsant, antihyperglycemic, antimicrobial, antineoplastic, cardiovascular, opioid, or sedative-hypnotic agents overdose, N-acetylcysteine, physostigmine, l-carnitine, dextrose, octreotide, pyridoxine, dexrazoxane, leucovorin, glucarpidase, atropine, calcium, digoxin-specific antibody fragments, glucagon, high-dose insulin euglycemia therapy, lipid emulsion, magnesium, sodium bicarbonate, naloxone, and flumazenil are specifically reviewed. As might be anticipated from the fact that supportive care suffices for the majority of poisoned patients, a typical study of routine administration of charcoal following oral overdose of primarily benzodiazepines, acetaminophen, and selective serotonin reuptake inhibitors could not demonstrate benefit [16, 17, 23] . Patient characteristics suggesting extracorporeal therapy include signs or symptoms of significant end organ toxicity; impaired elimination secondary to baseline comorbidities or critical illness-induced hypoperfusion; inability to tolerate or refractory to antidotal strategies (such as bicarbonate or saline); inadequate response to supportive care measures; concurrent electrolyte derangements (e.g., metformin-associated lactic acidosis); or serum drug concentrations historically associated with severe outcome [127] .
      cache = ./cache/cord-007798-9ht7cqhu.txt
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=== reduce.pl bib ===
         id = cord-000182-ni6iyzdn
     author = He, Zhisong
      title = Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features
       date = 2010-03-11
      pages = 
  extension = .txt
       mime = text/plain
      words = 6037
  sentences = 305
     flesch = 46
    summary = title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features Many researchers have made lots of efforts to develop useful algorithms and softwares to investigate various drug-related biological problems, such as HIV protease cleavage site prediction [18, 19] , identification of GPCR (G protein-coupled receptors) type [20, 21] , protein signal peptide prediction [22] , protein subcellular location prediction [23, 24, 25] , analysis of specificity of GalNAc-transferase protein [26] , identification of protease type [27, 28] , membrane protein type prediction [29, 30, 31, 32] , and a series of relevant webserver predictors as summarized in a recent review [33] . The drug-target benchmark datasets thus obtained for enzymes, ion-channels, GPCRs, and nuclear receptors are given in Online Supporting Information S1, S2, S3, and S4, respectively. Prediction of G-protein-coupled receptor classes based on the concept of Chou's pseudo amino acid composition: an approach from discrete wavelet transform
      cache = ./cache/cord-000182-ni6iyzdn.txt
       txt  = ./txt/cord-000182-ni6iyzdn.txt
=== reduce.pl bib ===
         id = cord-018595-x3tleomb
     author = Dodiuk-Gad, Roni P.
      title = Adverse Medication Reactions
       date = 2017-04-25
      pages = 
  extension = .txt
       mime = text/plain
      words = 16304
  sentences = 910
     flesch = 39
    summary = 2. Delayed-type drug hypersensitivity: Delayed-type drug hypersensitivity reactions usually take several days to weeks following drug exposure, with variable clinical presentations that may include Maculopapular Eruption (MPE), Fixed Drug Eruption (FDE), Acute Generalized Exanthematous Pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Examples of strong associations of HLA alleles with specific drug-induced hypersensitivity reactions include abacavir, nevirapine, carbamazepine, and allopurinol (Table 25. [61] , who reported the weak associations of HLA-A29, B12, and MPE maculopapular drug eruption, DRESS drug reaction with eosinophilia and systemic symptoms, SJS/TEN Stevens-Johnson syndrome/toxic epidermal necrolysis DR7 in sulfonamide-related TEN, and HLA-A2, B12 in oxicam-related TEN in Europeans [61] . Drug specific cytotoxic T-cells in the skin lesions of a patient with toxic epidermal necrolysis
      cache = ./cache/cord-018595-x3tleomb.txt
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=== reduce.pl bib ===
         id = cord-007511-5d5authn
     author = Gil, JP
      title = CYP2C8 and antimalaria drug efficacy
       date = 2007-02-07
      pages = 
  extension = .txt
       mime = text/plain
      words = 6628
  sentences = 363
     flesch = 47
    summary = By combining it with published in vitro pharmacodynamic and drug metabolism information, we review and predict the possible relevance, or lack of, of CYP2C8 polymorphisms in the present and future efficacy of amodiaquine. By combining it with published in vitro pharmacodynamic and drug metabolism information, we review and predict the possible relevance, or lack of, of CYP2C8 polymorphisms in the present and future efficacy of amodiaquine. This leaves drug therapy as the main tool for the global treatment and control of the disease, presently in the successful shape of the highly effective combination of artemisinine (ART) derivatives with longer half-life partners [4] .
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=== reduce.pl bib ===
         id = cord-016283-b6yywn9f
     author = Hasan, Ashfaq
      title = Clinical Aspects and Principles of Management of Tuberculosis
       date = 2019-08-07
      pages = 
  extension = .txt
       mime = text/plain
      words = 6930
  sentences = 347
     flesch = 46
    summary = Notwithstanding the advances in modern science, clinical diagnosis sometimes remains elusive, owing principally to the frequent paucibacillary occurrence of the disease and the slow doubling time of the organism; empiric treatment is often fraught with risks in the era of increasing drug resistance. The line probe assays (LPA) can permit rapid identification of specific gene markers associated with rifampicin resistance alone or in combination with isoniazid, and provide clinically relevant information about the level of INH resistance (low level associated with the INH-A gene; versus high level associated with the kat-G gene) (WHO treatment guidance for drug resistant tuberculosis 2016). Anti-tubercular drugs require to be supplemented with carefully monitored steroid therapy in two circumstances: tubercular meningitis (a short course of dexamethasone or prednisolone is typically given, tapered over 6 to 8 weeks) and tuberculous pericarditis (Guidelines for treatment of drug-susceptible tuberculosis and patient care 2017).
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         id = cord-017583-72mbsib7
     author = Devarajan, Padma V.
      title = Infectious Diseases: Need for Targeted Drug Delivery
       date = 2014-09-01
      pages = 
  extension = .txt
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      words = 8877
  sentences = 531
     flesch = 32
    summary = The adaptive mechanisms of Mycobacterium tuberculosis to survive inside the macrophages are prevention of fusion of the phagosome with lysosomes by producing tryptophan-aspartate-containing coat protein (TACO). In case of Mycobacterium tuberculosis infection, alveolar macrophages (dust cells), along with dendritic cells engulf bacteria and exhibit innate as well as an adaptive immune response. Infection of macrophages leads to changes in the expression pattern of the concerned receptors, which can be exploited for targeted drug delivery employing nanocarriers. Table 3 .6 is a summary of the important receptors on macrophages and illustrative examples of ligands for the same that could play a role in designing targeted nanocarriers for infectious disease therapy. Targeted drug delivery to enhance effi cacy and shorten treatment duration in disseminated Mycobacterium avium infection in mi host factors infl uencing the preferential localization of sterically stabilized liposomes in klebsiella pneumoniae-infected rat lung tissue Targeted intracellular delivery of antituberculosis drugs to mycobacterium tuberculosis-infected macrophages via functionalized mesoporous silica nanoparticles
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         id = cord-024833-e6vcf4un
     author = nan
      title = Forum
       date = 2019-12-19
      pages = 
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      words = 8110
  sentences = 391
     flesch = 48
    summary = Approximately 80% of US hospitals rely on data and recommendations from the ECRI Institute to protect patients from unsafe practices and ineffective products, while the ISMP's efforts to improve safety in patients have resulted in changes to clinical practice and public policy, including improvements in drug labelling, packaging, preparation and administration. The FDA has now announced the availability of a draft document entitled "Best Practices in Drug and Biological Product Postmarket Safety Surveillance for FDA Staff", which outlines the agency's approach to timely postmarketing analyses of drugs and biologics, and "includes a high-level overview of tools, methods, and signal detection and evaluation activities, using varied data sources, for drug safety surveillance to provide a broader context and a general overview of our overarching effort and commitment in this area", says Woodcock. Analysis of spontaneous ADR reports to the European Medicine Agency's EudraVigilance database has identified new safety signals for asthma drugs in paediatric patients, say authors of a study published in Drug Safety.
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         id = cord-033723-jy5fdsp9
     author = Orhobor, Oghenejokpeme I.
      title = Generating Explainable and Effective Data Descriptors Using Relational Learning: Application to Cancer Biology
       date = 2020-09-19
      pages = 
  extension = .txt
       mime = text/plain
      words = 4013
  sentences = 229
     flesch = 52
    summary = In many scientific problems explainable models are required, and the input data is semantically complex and unsuitable for DNNs. This is true in the fundamental problem of understanding the mechanism of cancer drugs, which requires complex background knowledge about the functions of genes/proteins, their cells, and the molecular structure of the drugs. This has changed with the success of deep neural-networks (DNNs), which has been based on their capacity to utilize multiple neural network layers, and large amounts of data, to learn how to convert raw propositional descriptors (e.g., image pixel values) into richer internal representations that are effective for learning. We hypothesized that we could improve both ML model explainability, and predictive accuracy, by including additional background knowledge in the learning process using a hybrid RL approach. Furthermore, there exist several other approaches for learning representations from graph or inherently relational data [3, 13] with varying levels of predictive performance and interpretability.
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         id = cord-015334-8p124rwp
     author = nan
      title = ESCP 36th European Symposium on Clinical Pharmacy ‘Implementing Clinical Pharmacy in Community and Hospital Settings: Sharing the Experience’, Istanbul, Turkey 25–27 October 2007; Abstracts
       date = 2008-06-11
      pages = 
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      words = 51143
  sentences = 3291
     flesch = 51
    summary = Based on the results of the pharmacoeconomic analysis, development of clinical pharmacy and CIVAS for some drugs will be discussed with the paediatric department Background and Objective: Studies show that up to 38% of patients starting treatment with antidepressants fill only a single prescription at the pharmacy, apparently not accepting treatment. Main Outcome Measures: Data collected were: nurses' profile (age, length of service, competencies' self-assessment), knowledge on drugs prescribed to their patients (usage, administration, side-effects, drug interactions…), use of existing tools (i.e. drugs database) and possible tools to be developed by the pharmacy ward to help them in their daily practice. The objectives were:(1)To identify the most relevant minor ailments, agreeing on the specific criteria for referral to the GP.(2)To select the non-prescription drugs, with evidence of safety and effectiveness, for the treatment of the identified minor ailments Design: Qualitative study with an expert panel which was made up of 2 primary care physician from SEMFYC and six community pharmacists (two members of SEFAC and four members of GIAF-UGR).
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         id = cord-104431-3rblzyry
     author = Hill, Andrew
      title = Minimum costs to manufacture new treatments for COVID-19
       date = 2020-04-30
      pages = 
  extension = .txt
       mime = text/plain
      words = 5494
  sentences = 336
     flesch = 56
    summary = RESULTS: Minimum estimated costs of production were US $0.93/day for remdesivir, $1.45/day for favipiravir, $0.08/day for hydroxychloroquine, $0.02/day for chloroquine, $0.10/day for azithromycin, $0.28/day for lopinavir/ritonavir, $0.39/day for sofosbuvir/daclatasvir and $1.09/day for pirfenidone. large donor organisations such as the global Fund for aiDs, TB and Malaria (gFaTM) and the President's emergency Plan for aiDs relief (PePFar) order drugs to treat >20 million people with hiV, at prices close to the cost of production [20, 21] . We used all available costing data for each drug aPi found on Panjiva, excluding shipments <1kg in size, alongside the lowest and highest 15% of results based on prices per kg. Minimum costs to manufacture new treatments for cOViD-19 67 Different dosing protocols are being used for hydroxychloroquine, including 600 mg daily in the small, open-label, non-randomised French study by gautret et al.
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         id = cord-203232-1nnqx1g9
     author = Canturk, Semih
      title = Machine-Learning Driven Drug Repurposing for COVID-19
       date = 2020-06-25
      pages = 
  extension = .txt
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      words = 5023
  sentences = 257
     flesch = 52
    summary = Using the National Center for Biotechnology Information virus protein database and the DrugVirus database, which provides a comprehensive report of broad-spectrum antiviral agents (BSAAs) and viruses they inhibit, we trained ANN models with virus protein sequences as inputs and antiviral agents deemed safe-in-humans as outputs. Using sequences for SARS-CoV-2 (the coronavirus that causes COVID-19) as inputs to the trained models produces outputs of tentative safe-in-human antiviral candidates for treating COVID-19. For Experiment II, we split the data on virus species, meaning the models were forced to predict drugs for a species that it was not trained on, and have to detect peptide substructures in the amino-acid sequences to suggest drugs. In post-processing, we applied a threshold to the sigmoid function outputs of the neural network, where we assigned each drug a probability of being a potential antiviral for a given amino acid sequence.
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         id = cord-102823-zult69f2
     author = Nguyen, Thin
      title = GraphDTA: Predicting drug–target binding affinity with graph neural networks
       date = 2020-10-02
      pages = 
  extension = .txt
       mime = text/plain
      words = 4962
  sentences = 283
     flesch = 56
    summary = We propose a new model called GraphDTA that represents drugs as graphs and uses graph neural networks to predict drug--target affinity. We show that graph neural networks not only predict drug--target affinity better than non-deep learning models, but also outperform competing deep learning methods. Our results confirm that deep learning models are appropriate for drug--target binding affinity prediction, and that representing drugs as graphs can lead to further improvements. In this article, we propose GraphDTA, a new neural network architecture capable of directly modelling drugs as molecular graphs, and show that this approach outperforms state-of-the-art deep learning models on two drug-target affinity prediction benchmarks. Although we focus on drug-target affinity prediction, our GraphDTA model is a generic solution for any similar problem where either data input can be represented as a graph.
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         id = cord-023509-tvqpv6fp
     author = Corrin, Bryan
      title = Occupational, environmental and iatrogenic lung disease
       date = 2011-03-02
      pages = 
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      words = 42576
  sentences = 2457
     flesch = 45
    summary = As a general rule, exposure to silica dust extends over many years, often 20 or more, before the symptoms of silicosis first appear: by the time the disease becomes overt clinically, much irreparable damage has been inflicted on the lungs. Confusingly, the term 'acute silicosis' has since been applied to a further effect of heavy dust exposure in tunnellers, sand blasters and silica flour workers, namely pulmonary alveolar lipoproteinosis (see below), 71, 72 whilst the terms 'accelerated silicosis' or 'cellular phase silicosis' have been substituted for 'acute silicosis' in referring to the rapid development of early cellular lesions. Asbestosis is defined as diffuse interstitial fibrosis of the lung caused by exposure to asbestos dust. The finely divided fume of several metals is highly toxic to the lungs and capable of producing severe acute and chronic damage to both the conductive airways and the alveoli, resulting in acute tracheobronchitis and bronchiolitis, diffuse alveolar damage, obliterative bronchiolitis and pulmonary fibrosis.
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         id = cord-232446-vvb2ffhv
     author = Mongia, Aanchal
      title = A computational approach to aid clinicians in selecting anti-viral drugs for COVID-19 trials
       date = 2020-07-03
      pages = 
  extension = .txt
       mime = text/plain
      words = 7123
  sentences = 382
     flesch = 47
    summary = In view to assist acceleration of this process (by pruning down the search space), we create and share a publicly available DVA database, along with a number of matrix completion techniques (mentioned above) for drug-virus association prediction. Such a computational approach requires the chemical structure of the drugs and, in case of graph-regularized matrix completion techniques, the genome of the viruses, or existing associations otherwise. A clear observation from the experiments is that the graph regularized-based matrix completion algorithms that incorporate the similarity information associated with the drugs and viruses, perform fairly well giving an AUC greater or equal than 0.83 in CV1. It can be noted that the standard matrix completion methods, which do not take into account the metadata, fail to learn from the association data giving a near-random performance as far as the prediction on novel viruses is concerned, depicting how very important the similarity information is.
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         id = cord-256852-lrz17bdx
     author = Nayyar, Gaurvika M. L.
      title = Responding to the Pandemic of Falsified Medicines
       date = 2015-06-03
      pages = 
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      words = 4208
  sentences = 201
     flesch = 39
    summary = 15 The U.S. Institute of Medicine (IOM) has published a report "Countering the Problem of Falsified and Substandard Drugs." 16 The IOM recommendations to "stem the global trade" in such products are laudable in advising that the U.S. Food and Drug Administration (FDA), the National Institute of Standards and Technology, and other U.S. and international pharmaceutical and financing agencies be more actively involved in setting standards and financing improvements; yet this report falls far short of making a strong call for standardized, agreed-upon quality assessment technologies; an international law convention; and a more activist, internationally recognized lead organization, all three of which are essential for stopping the many health threats of fake drugs.
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         id = cord-214795-8jweuq50
     author = Mongia, Aanchal
      title = DeepVir -- Graphical Deep Matrix Factorization for"In Silico"Antiviral Repositioning: Application to COVID-19
       date = 2020-09-22
      pages = 
  extension = .txt
       mime = text/plain
      words = 6420
  sentences = 369
     flesch = 47
    summary = Results on our curated RNA drug virus association (DVA) dataset shows that the proposed approach excels over state-of-the-art graph regularized matrix completion techniques. It shows how the matrix completion framework can be used to computationally predict the drugs that could be effective against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus responsible for the ongoing pandemic, COVID-19 (COrona VIrus Disease-2019). In this present work, we propose to solve the problem of drug-virus association prediction via graph regularized deep matrix factorization. Among all the methodologies compared in [52] , graph regularized matrix factorization based technique (GRMF) provided the best results for the validation setting where drugs are predicted for novel viruses. In our proposed technique, multi-graph regularization is incorporated in the deep matrix factorization formulation with the aim to incorporate the metadata associated with the drugs and viruses in the form of similarity information as shown below:
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         id = cord-265848-afkeuwup
     author = nan
      title = Chapter 2 Emergency Management of Poisoning
       date = 2007-12-31
      pages = 
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      words = 27412
  sentences = 1589
     flesch = 39
    summary = With the use of drugs having a short duration of action, RSI also is advantageous because it is a measure that permits temporary airway control for the patient with mildly compromised airway reflexes who requires gastrointestinal decontamination (lavage followed by activated charcoal administration) but who does not require prolonged intubation. The management of gastrointestinal disturbance in the toxic patient includes following the general principles of blood, fluid, and electrolyte resuscitation, when indicated; judicious use of parenteral antiemetics to control persistent vomiting; specific measures such as antidotal therapy (e.g., in iron or organophosphate poisoning); or interventional therapy, such as charcoal hemoperfusion (in theophylline overdose) or hemodialysis (in lithium overdose), when indicated.
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         id = cord-261311-j6bmgmhz
     author = Parreiras Martins, Maria Auxiliadora
      title = Preparedness of pharmacists to respond to the emergency of the COVID-19 pandemic in Brazil: a comprehensive overview
       date = 2020-07-31
      pages = 
  extension = .txt
       mime = text/plain
      words = 4307
  sentences = 206
     flesch = 37
    summary = COVID-19 patients may present high risk in the use of medications and clinical pharmacists can contribute substantially as part of a multidisciplinary team to improve outcomes in drug therapy in severe and critical illness. The course of an intense inflammatory process leads to alterations in many Review of patients' medical history Provision of real-time assessment and evidence-based (when possible) advice on drug therapy Support on safe use of medications brought from home Medication reconciliation at different levels of transition of care Simplification of drug administration schedule to reduce the exposure of nurses to COVID-19 patients Monitoring of potential drug-drug, drug-food interactions and adverse drug reactions Adjustments in dosing regimens according to liver and kidney functions Prevention of medication errors Optimization of drug therapy and electrolytes to minimize the risk of prolonged corrected QT intervals and torsade de pointes Support on lung-protective ventilation and neuromuscular blocking agents to facilitate ventilator synchrony Provision of conservative fluid strategies and monitoring of vasopressors use Monitoring of empirical antibiotics for suspected bacterial co-infection with rigorous de-escalation Employment of FASTHUG-MAIDENS mnemonic to identify drug-related problems in intensive care units Support on drug information to patients and multidisciplinary teams, following biosafety protocols Considerations on special situations (pediatrics, older adults, people with chronic diseases, allergies) Research and continuing education Precise documentation of pharmaceutical interventions laboratory tests in patients with acute or severe/critical illness.
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         id = cord-253115-ekgdsv4f
     author = Mehta, Meenu
      title = Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases
       date = 2019-08-01
      pages = 
  extension = .txt
       mime = text/plain
      words = 7317
  sentences = 457
     flesch = 39
    summary = Commonly used drug delivery systems for respiratory diseases are polymer-based, lipid-based and peptide-based, and among these three, the lipid-based carriers are the most commonly used vectors for delivering RNAi. They include solid lipid nanoparticles, cationic liposomes, lipidoids, solid nanostructured lipid carriers and pH-responsive lipids [26] . The effective delivery of the drug and siRNA induced cell death of lung tumor cells by targeted gene silencing [56] . Glud et al., investigated pulmonary gene silencing effect of small interfering locked nucleic acid (siLNAs), targeting enhanced-greenfluorescent-protein (EGFP) in lung bronchoepithelium upon intravenous delivery of naked siLNAs and intranasal delivery of naked siLNA or chitosan based siLNA mucoadhesive nanoparticles. This study demonstrated that SAMiRNA nanoparticle is a stable siRNA silencing platform with less toxicity for effective in vivo targeting of genes involved in the pathogenesis of respiratory diseases [96] . Overcoming cisplatin resistance in non-small cell lung cancer with Mad2 silencing siRNA delivered systemically using EGFR-targeted chitosan nanoparticles
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         id = cord-258614-7unadw41
     author = Ogidigo, Joyce Oloaigbe
      title = Natural phyto, compounds as possible noncovalent inhibitors against SARS-CoV2 protease: computational approach
       date = 2020-10-25
      pages = 
  extension = .txt
       mime = text/plain
      words = 8459
  sentences = 416
     flesch = 47
    summary = Structure-based virtual screening and molecular dynamics (MD) simulation have been employed to study their inhibitory potential against the main protease (M(pro)) SARS-CoV-2. These phytocompounds showed strong and stable interactions with the active site amino acid residues of SARS-CoV-2 Mpro similar to the reference compound. Results obtained from this study showed that momordicine and momordiciode F2 exhibited good inhibition potential (best MMGBA-binding energies; −41.1 and −43.4 kcal/mol) against the M(pro) of SARS-CoV-2 when compared with FDA reference anti-viral drugs (Ribavirin, remdesivir and hydroxychloroquine). Thus, among the 86 phytocompounds and 3 antiviral drugs screened (Supplementary material Table S1 ), 6 phyto ligands exhibited appreciable binding energies against the SARS-CoV-2 M pro and strong interactions within the binding pocket. Analysis of the per-residue additional showed that studied compounds interact with these key amino acid residues in the active site of the main protease, suggesting that these phytocompounds could emerge as ideal candidate's inhibitors against SARS-CoV-2 M pro and another virus protease.
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         id = cord-256118-gxhhwqdd
     author = Abadie, R.
      title = “Caballo”: risk environments, drug sharing and the emergence of a hepatitis C virus epidemic among people who inject drugs in Puerto Rico
       date = 2020-10-23
      pages = 
  extension = .txt
       mime = text/plain
      words = 7854
  sentences = 337
     flesch = 54
    summary = Based on a study of PWID in Colorado, Koester (2005) suggests that indirect sharing, which happens when powder drugs are diluted in water before been divided up in a cooker with the help of a syringe, is an efficient way of distributing drugs among injection partners. Nested within a study of social networks and HIV/ HCV risk among PWID in rural Puerto Rico, we propose an ethnographically informed approach to "caballo", the joint acquisition and sharing of drugs, as a window into the social production of an HCV epidemic among PWID. While drug sharing arrangements among PWID have been amply documented, an ethnographic study of caballo in Puerto Rico will illuminate the social context behind the joint acquisition and use of drugs and its related epidemiological risk.
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         id = cord-267979-k70gnrdw
     author = Yıldız-Peköz, Ayca
      title = Advances in Pulmonary Drug Delivery
       date = 2020-09-23
      pages = 
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      words = 3257
  sentences = 159
     flesch = 38
    summary = This Special Issue brings together recent advances in the areas of inhalation device testing, aerosol formulation development, use of in vitro and in silico models in pulmonary drug deposition and drug disposition studies, and pulmonary delivery of complex drugs, such as vaccines, antibiotics and peptides, to or via the lungs. The development of modern-day inhalers, e.g., pressurised metered-dose inhalers (pMDIs) and more recently, dry powder inhalers (DPIs), jet and vibrating mesh nebulisers (VMNs), and soft mist inhalers (SMIs), has given pulmonary drug delivery a momentum boost that transformed a therapeutic niche into a market predicted to hit US$41.5 billion by 2026 [1] . Development of an innovative, carrier-based dry powder inhalation formulation containing spray-dried meloxicam potassium to improve the in vitro and in silico aerodynamic properties Excipient interactions in glucagon dry powder inhaler formulation for pulmonary delivery Inhalable dry powder of bedaquiline for pulmonary tuberculosis: In vitro physicochemical characterization, antimicrobial activity and safety studies
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         id = cord-267608-0odu8lus
     author = Chen, Daohong
      title = Innovative highlights of clinical drug trial design
       date = 2020-06-03
      pages = 
  extension = .txt
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      words = 4164
  sentences = 155
     flesch = 28
    summary = Accordingly taking the advantage of interim analysis based on novel biomarker approach for detecting the pathogenesis-specific molecular alteration(s), an adaptive clinical study can select the drug-sensitive sub-population from patients with initially targeted disease or an alternative indication, to continue the investigation for an optimized therapeutic efficacy [7] . While human bioequivalence study is increasingly contributing to evaluation of emerging formulation and bio-similar agents besides chemical generics [4] , several adaptive trial designs have been capable of translating the scientific breakthroughs into novel therapeutic benefits with shorter processing time and lower financial costs, to address the unmet clinical needs [3, 19] . Of note, to preserve the strength of clear defining efficacy and safety of tested drugs, the innovative designs of clinical study are substantially overlapped with classic trial protocols of three phases which still serve as the mainstream approach of clinical investigation [3, 7] .
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         id = cord-203191-7ftg6bfx
     author = Guo, Kai
      title = Identification of Repurposal Drugs and Adverse Drug Reactions for Various Courses of Coronavirus Disease 2019 (COVID-19) Based on Single-cell RNA Sequencing Data
       date = 2020-05-16
      pages = 
  extension = .txt
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      words = 3729
  sentences = 184
     flesch = 43
    summary = title: Identification of Repurposal Drugs and Adverse Drug Reactions for Various Courses of Coronavirus Disease 2019 (COVID-19) Based on Single-cell RNA Sequencing Data To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.S. FDA approved drugs and pre-clinical small-molecule compounds by integrating the gene expression perturbation data by chemicals from the Library of Integrated Network-Based Cellular Signatures (LINCS) project with publically available single-cell RNA sequencing dataset from mild and severe COVID-19 patients. We also collected a list of differentially expressed genes (DEGs) in SARS-CoV-2-infected lung BALF using a bulk RNA-Seq analysis to compare against the single-cell-based data. Repurposing analysis in severe COVID-19 patients 60 potent drugs were also selected in severe cases compared to controls (severe vs healthy group) according to their average CS between the replicates, and 25 of them involved in more than one cell subtype ( Figure 2B , Supplementary Tables S8 & S9) .
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         id = cord-263840-1t4ykc01
     author = Altay, Ozlem
      title = Current status of COVID-19 therapies and drug repositioning applications
       date = 2020-06-20
      pages = 
  extension = .txt
       mime = text/plain
      words = 2099
  sentences = 140
     flesch = 44
    summary = Summary The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for treatment of COVID-19. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. At the genome 60 level, SARS-CoV-2 has 79·5% homology to SARS CoVCoV-2 and other coronaviruses, and its relative ease of sample acquisition and study, it has been widely 75 accepted that drug repositioning is a promising approach to make available an effective, safety-assured 76 treatment in a timely manner. In this review, we summarize diagnosis approaches, risk groups, available 77 treatment options, and drug repositioning studies related to COVID-19. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 525 2019 (COVID-19): The experience of clinical immunologists from China
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         id = cord-262442-kjgpriow
     author = Scalia, Santo
      title = Quercetin solid lipid microparticles: A flavonoid for inhalation lung delivery
       date = 2013-05-13
      pages = 
  extension = .txt
       mime = text/plain
      words = 5525
  sentences = 310
     flesch = 53
    summary = The quercetin SLMs were characterised for morphology, drug loading (15.5% ± 0.6, which corresponded to an encapsulation efficiency of 71.4%), particle size distribution, response to humidity, crystallinity, thermal behaviour and in vitro respirable fraction. Furthermore, the toxicity and the in vitro transport of the SLMs on an air liquid interface model of the Calu-3 cell line were also investigated using a modified twin-stage impinger apparatus. RESULTS: Results showed that quercetin SLMs could be formulated as dry powder suitable for inhalation drug delivery (20.5 ± 3.3% fine particle fraction ⩽4.46 μm) that was absorbed, via a linear kinetic model across the Calu-3 monolayer (22.32 ± 1.51% over 4 h). A modified in vitro aerosol testing apparatus (twin stage impinger TSI, Radleys, Essex, UK) that allows the attachment of a Transwell containing Calu-3 epithelial cells was used to study the mechanis m of drug deposition, dissolution and diffusion/transp ort (Haghi et al., 2010 (Haghi et al., , 2012 .
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         id = cord-014687-0am4l5ms
     author = nan
      title = SPR 2012
       date = 2012-03-29
      pages = 
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      words = 98592
  sentences = 5600
     flesch = 43
    summary = This presentation will focus on recent developments that have lead to a better understanding of the embryopathogenesis for fibropolycystic liver diseases (including choledochal cysts and Caroli disease), histopathological findings that have led to new classification systems for of pediatric vascular anomalies, technological advances and contrast agents in magnetic resonance imaging that are useful to characterize and limit the differential diagnosis of hepatic masses. Disclosure: Dr. Annapragada has indicated that he is a stock holder and consultant for Marval Biosciences Inc. Paper #: PA-067 Cardiovascular Image Quality Using a Nanoparticle CT Contrast Agent: Preliminary Studies in a Pig Model Rajesh Krishnamurthy, Radiology, Texas Children's Hospital, rxkrishn@texaschildrens.org; Ketan Ghaghada, Prakash Masand, Abhay Divekar, Eric Hoffman, Ananth Annapragada Purpose or Case Report: Image quality in a separate study using a long circulating, liposomal-based nanoscale blood pool iodinated contrast agent (NCTX) suggests clinical utility in pediatrics, potentially reducing difficulties in contrast-CT of children with congenital heart disease (CHD) including the size of intravenous cannula, need for accurate timing, inability to simultaneously opacify multiple targets of interest (requiring repeated contrast administration and/or repeated imaging).
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         id = cord-032561-x3qbqy69
     author = Liu, Gengqi
      title = Stimulus-Responsive Nanomedicines for Disease Diagnosis and Treatment
       date = 2020-09-02
      pages = 
  extension = .txt
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      words = 25208
  sentences = 1664
     flesch = 46
    summary = demonstrated that nanodrug carriers with diselenides could release more drugs using poly (ester carbamate) triblock copolymers (PAUR-Se-Se) with Se-Se bonds compared with poly (ester carbamate) triblock copolymers (PAUR-S-S) [54, 55] Thioether Selenium Tellurium Besides the development of drug delivery systems, pH-responsive systems can also be used for tumor detection and image-guided surgery [46] . demonstrated that nanodrug carriers with diselenides could release more drugs using poly (ester carbamate) triblock copolymers (PAUR-Se-Se) with Se-Se bonds compared with poly (ester carbamate) triblock copolymers (PAUR-S-S) [65] PBA/PBE Besides the development of drug delivery systems, pH-responsive systems can also be used for tumor detection and image-guided surgery [46] . Therefore, pH responsive system can be combined with other stimulus conditions such as light, redox, enzymes and others with the aim of improved selectivity for drug release in diseased tissues [47, 48] . In addition to photothermal therapy and PDT, light-responsive strategies have also been applied in the design of prodrug systems and drug delivery carriers.
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         id = cord-268088-y4vg7frb
     author = Montané, Xavier
      title = Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy
       date = 2020-07-23
      pages = 
  extension = .txt
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      words = 11101
  sentences = 581
     flesch = 42
    summary = Among the natural compounds that produce beneficial effects on human health, polyphenols have shown potential therapeutic applications in cancer due to their protective functions in plants, their use as food additives, and their excellent antioxidant properties. This review shows a wide range of trials in which polyphenolic compounds play a crucial role as anticancer medicines alone or in combination with other drugs at different stages of cancer: cancer initiation, promotion, and growth or progression. In point of fact, studies demonstrated that resveratrol has in vitro effects against a large range of human tumors: breast, skin, ovary, stomach, prostate, colon, liver, pancreas, cervix, thyroid carcinoma cells, lymphoid, and myeloid cancer cells [22] . In point of fact, studies demonstrated that resveratrol has in vitro effects against a large range of human tumors: breast, skin, ovary, stomach, prostate, colon, liver, pancreas, cervix, thyroid carcinoma cells, lymphoid, and myeloid cancer cells [22] .
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         id = cord-273716-vv3pyft4
     author = Khosravi-Darani, Kianoush
      title = The role of high-resolution imaging in the evaluation of nanosystems for bioactive encapsulation and targeted nanotherapy
       date = 2007-07-03
      pages = 
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      words = 10230
  sentences = 514
     flesch = 34
    summary = This review will focus on nanoscale bioactive delivery and targeting mechanisms and the role of high-resolution imaging techniques in the evaluation and development of nanocarriers. Applications of nanotechnology in medicine are particularly promising and areas such as molecular imaging, disease diagnosis, bioactive encapsulation and targeted delivery at specific sites in the body are being intensively investigated and some products undergoing clinical trials (Moghimi et al., 2005; Shaffer, 2005; Wilkinson, 2003) . Usefulness of high-resolution scanning probe imaging in the study of lipidic gene transfer vectors and the interaction between liposomes and DNA molecules have recently been reviewed by Mozafari et al. Modern nanocarrier systems such as nanoliposomes, niosomes, solid lipid nanoparticles (Saupe and Rades, 2006) , as well as silicon-, carbon-and polymer-based nanocarriers play an important role in controlled delivery of the bioactive agents to the desired site of action, limiting the side effects at nontarget sites (Ruozi et al., 2007) .
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         id = cord-275772-pmf6stua
     author = Jourdan, Jean‐Pierre
      title = Drug repositioning: a brief overview
       date = 2020-04-17
      pages = 
  extension = .txt
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      words = 3239
  sentences = 160
     flesch = 43
    summary = Drug repositioning lies in repurposing an active pharmaceutical ingredient that is already on the market for a new indication. This original definition of drug repositioning has since been extended to include active substances that failed the clinical phase of their development on account of their toxicity or insufficient efficacy, as well as drugs withdrawn from the market because of safety concerns. Instead, repositioning makes use in a new indication of either the biological properties for which the drug has already been approved (possibly according to a different formulation, at a new dose or via a new route of administration), or the side properties of a drug that are responsible for its adverse effects. This example illustrates how even drugs with an exceptionally poor toxicity profile can be repositioned if the new indication is a rare disease (the estimated incidence of leprosy is 250 000 cases per year according to http://www.orpha.net, accessed November, 21th 2019). Drug repositioning: identifying and developing new uses for existing drugs
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         id = cord-274474-u2fdicgz
     author = Majumder, Joydeb
      title = Targeted Nanotherapeutics for Respiratory Diseases: Cancer, Fibrosis, and Coronavirus
       date = 2020-10-13
      pages = 
  extension = .txt
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      words = 10098
  sentences = 634
     flesch = 46
    summary = The present review summarizes recent advances in the development of nanocarrier based therapeutics for local and targeted delivery of drugs, nucleic acids and imaging agents for diagnostics and treatment of various diseases such as cancer, cystic fibrosis, and coronavirus. [1, 2] Therefore, methods of developing new therapeutic solutions as well as improving the current therapies for the common lung diseases such as asthma, cystic fibrosis, chronic obstructive pulmonary disease, lung cancer, and coronavirus infections remain the main focus in the fields of targeted drug delivery. In this review, we will summarize recent reports on the development of lipid and polymer based nanocarriers for targeted delivery of drugs and nucleic acids for the treatment of lung cancer. In a similar study, we used a complex liposomal drug delivery system containing anticancer drug doxorubicin and both MRP1 and BCL2 targeting antisense oligonucleotides for inhalation treatment in lung cancer cells.
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         id = cord-257496-mirh80gn
     author = Hickey, Anthony J.
      title = Emerging trends in inhaled drug delivery
       date = 2020-07-12
      pages = 
  extension = .txt
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      words = 4689
  sentences = 258
     flesch = 42
    summary = These product variables in combination with patient variables, including co-ordination skill during inhaler use, intrinsic lung biology, disease and consequent pulmonary function, contribute to drug safety and efficacy outcomes. Figure 1 summarizes the requirements of matching the therapeutic agent to the desired treatment outcome while considering the overall host system barriers (deposition and clearance mechanisms) and target (receptor or pathogen) biology guiding selection or development of a suitable drug delivery technology. However, recently the use of liposomes to aid in drug preparation and delivery and to aid in targeting of macrophages has advanced formulation options [28, 29] .The use of ethanol in the solutions delivered from the Respimat™ soft mist inhaler, e.g. tiotropium (Spiriva®, Boehringer Ingelheim) enhances the solubilization properties of the medium and facilitates a hand held aqueous based system with accurate and reproducible performance in delivering very low doses (<10 µg) on a single breath analogous to a metered dose inhaler [30, 31] . The addition of low-density lipid particles to HFA as a dispersant for micronized drug has allowed for a range of new metered dose inhaler products to come to market [40] .
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         id = cord-289321-ahl46ql9
     author = van Buuren, Nicholas
      title = Transmission genetics of drug-resistant hepatitis C virus
       date = 2018-03-28
      pages = 
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      words = 7817
  sentences = 394
     flesch = 48
    summary = Differential visualization of drug-resistant and -susceptible RNA genomes within cells revealed that resistant variants of NS3/4A protease and NS5A phosphoprotein are cis-dominant, ensuring their direct selection from complex environments. Our goal was to screen the HCV-encoded viral proteins that are current targets of antiviral compounds to determine the intracellular dominance relationships between drug-resistant and drug-susceptible genomes. To test whether susceptibility to NS5A inhibitors was dominant in the context of viral infections, we analyzed U, S, S + R and R cell populations by flow cytometry as previously performed for the NS3/4A inhibitor in Figure 3 . To test whether exogenously expressed drug-susceptible NS5A proteins could co-assemble with drug-resistant NS5A, we utilized the previously described HCV plasmid that expresses HA-tagged and GFP-tagged NS5A within the same polyprotein but does not support genome replication ( Figure 5A) . Failure of NS5A proteins to mix during infection is a likely explanation for the cis-dominance of drug resistance observed in cultured cells (Figure 4) .
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         id = cord-299225-exbdg3x9
     author = Guarnieri, Michael
      title = A Long-Term Study of a Lipid-Buprenorphine Implant in Rats
       date = 2018-07-09
      pages = 
  extension = .txt
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      words = 2662
  sentences = 159
     flesch = 50
    summary = These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery in laboratory animals and suggest that this model may be used to study long-term effects of opiate therapy. We examined the safety of cholesterol-triglyceride suspensions of buprenorphine in mice and rats using US Food and Drug Administration (FDA) Target Animal Safety (TAS) drug-development protocols. Histopathology examinations were performed on mice and rats treated with up to tenfold excess of the intended dose of drug and control animals following 4-and 12-day drug trials [19] [20] [21] . The label dose of 0.65 mg/kg of buprenorphine, which provides 2-3 days of clinically significant blood levels of drug, was established in bioequivalence trials and efficacy studies using male and female rats [21] . The objective of this study was to evaluate the long-term safety of a lipid suspension of buprenorphine for delivery of an opiate analgesic in female F344 rats.
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         id = cord-288026-vcp8o5xn
     author = DeStefano, Vincent
      title = Applications of PLA in Modern Medicine
       date = 2020-09-06
      pages = 
  extension = .txt
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      words = 8592
  sentences = 612
     flesch = 43
    summary = PLA has shown promise as a biomaterial in a plethora of healthcare applications such as tissue engineering or regenerative medicine, cardiovascular implants, dental niches, drug carriers, orthopedic interventions, cancer therapy, skin and tendon healing, and lastly medical tools / equipment. Blending with PLA-based stereocomplexed polymers, such as PLLA and PLDA, has demonstrated improved thermal stability and decelerated degradation rate. Manufacturing techniques may take advantage of the strong interactions between PDLA and PLLA blocks, which result from the formation of stereocomplex crystallization as well as improved mechanical properties and thermal stability. Degradation rate is dependent upon a number of factors: polymer composition, pH, device geometry, molecular weight, crystallinity, addition of drugs and/or additives, sterilization, mechanical stress, and fabrication processing. This is likely due to the controlled drug release and enhanced anti-tumor effects seen in doxorubicin-loaded PLA-based scaffolds, such as the one described by Niu et al. Effect of molecular weight and crystallinity on poly(lactic acid) mechanical properties
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         id = cord-285603-f4572w5m
     author = Ortega, Joseph T.
      title = Class A G Protein-Coupled Receptor Antagonist Famotidine as a Therapeutic Alternative against SARS-CoV2: An In Silico Analysis
       date = 2020-06-24
      pages = 
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      words = 5994
  sentences = 348
     flesch = 47
    summary = In order to gain a deeper understanding if the pharmacokinetic parameters of the SARS-CoV2 protease inhibitors could be related to positive outcomes in the therapy, we analyzed the ADME parameters of famotidine and compared with several known antiviral drugs such as ribavirin, lopinavir, and nafamostat, which were evaluated against SARS-CoV2. Chemical structures and administration, distribution, metabolism, and elimination (ADME) parameters for famotidine, ribavirin, lopinavir, and nafamostat, drugs that were evaluated as SARS-CoV2 inhibitors, are shown. Chemical structures and administration, distribution, metabolism, and elimination (ADME) parameters for famotidine, ribavirin, lopinavir, and nafamostat, drugs that were evaluated as SARS-CoV2 inhibitors, are shown. Altogether, in this study, we showed that famotidine could be used as an antiviral agent against SARS-CoV2, targeting proteases involved in the virus replication, mostly the main protease, as well as the viral PLpro and human host Tmprss2.
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         id = cord-292041-a65kfw80
     author = Orienti, Isabella
      title = Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment in COVID-19
       date = 2020-05-27
      pages = 
  extension = .txt
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      words = 6110
  sentences = 334
     flesch = 34
    summary = At present, there is no vaccine or effective standard treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (or coronavirus disease-19 (COVID-19)), which frequently leads to lethal pulmonary inflammatory responses. Therefore, due to its poly-pharmacology, fenretinide administration by pulmonary formulations may be expected to be protective against acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) caused by SARS-CoV infection and could represent a useful tool in a multimodal therapy aimed at establishing a rapid anti-inflammatory and antiviral effect. Pulmonary delivery of fenretinide could be a valuable tool in COVID-19 due to the possibility of obtaining a very high drug concentration in the airway and alveolar epithelia, thus triggering a rapid onset of local anti-inflammatory response. Moreover, the pulmonary administration of fenretinide, in combination with the drugs that are currently used in SARS-CoV-2 infection, could represent a new, effective tool in COVID-19 treatment.
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         id = cord-302018-3rlya16w
     author = Castells, Mariana C.
      title = Drug allergy labeling and delabeling in the coronavirus disease 2019 era: What is important and what do we need to know
       date = 2020-05-22
      pages = 
  extension = .txt
       mime = text/plain
      words = 1939
  sentences = 97
     flesch = 38
    summary = The topics covered in this issue provide the necessary and updated knowledge for all allergists involved in labeling and delabeling procedures, aiming to broaden drug choices and treatment options for patients in this unknown world of COVID-19 pandemic and other disease states. Target populations for receiving a drug allergy label include the following: (1) children with approximately 70,000 visits to the emergency department reported annually for adverse drug events with penicillins, cephalosporins, and sulfamethoxazole-trimethoprim as the most frequent medications; and (2) hospitalized patients with cancer, of whom 23% have a label of antibiotic allergy. The authors concluded that current and future efforts should focus on preventing penicillin allergy labels that can carry over into adulthood, providing education and decision support in the electronic medical record, and testing low-risk drug administration strategies in low-risk patients. As more mechanisms of drug allergy are uncovered and new biomarkers become available, they can be incorporated into this flexible classification, guiding clinicians toward an optimal approach for patient labeling or delabeling, treatment, and management.
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         id = cord-298369-66ifwtlp
     author = Smith, Sherri A.
      title = Pharmacokinetic and Pharmacodynamic Considerations for Drugs Binding to Alpha-1-Acid Glycoprotein
       date = 2018-12-28
      pages = 
  extension = .txt
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      words = 10621
  sentences = 491
     flesch = 46
    summary = The importance of plasma protein binding primarily resides in its impact on pharmacokinetic properties such as clearance (CL) and volume of distribution (V ss ), with serum albumin, lipoproteins and alpha-1 acid glycoprotein (AAG) being the major proteins involved in sequestering drugs in plasma (1) . While AAG represents a relatively small portion (~1-3%) of the total plasma proteins, compared to~60% composition of albumin, it can play a significant role in drug binding and pharmacokinetics (PK) (43) . Since AAG levels increase in most disease states (46) , drugs with a high affinity may demonstrate higher binding (lower fraction unbound, f u ) and altered PK properties (e.g. lower total CL), lower V ss . Effect of the plasticizer DEHP in blood collection bags on human plasma fraction unbound determination for Alpha-1-Acid Glycoprotein (AAG) binding drugs
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         id = cord-275828-c6d6nk7x
     author = Mikasa, Keiichi
      title = JAID/JSC Guidelines for the Treatment of Respiratory Infectious Diseases: The Japanese Association for Infectious Diseases/Japanese Society of Chemotherapy – The JAID/JSC Guide to Clinical Management of Infectious Disease/Guideline-preparing Committee Respiratory Infectious Disease WG
       date = 2016-07-31
      pages = 
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      words = 39672
  sentences = 2522
     flesch = 42
    summary = -SBT/ABPC, intravenous drip, 3 g/3e4 times a day -CTRX, intravenous drip, 1 g/twice a day or 2 g/once a day -CTX, intravenous drip, 1e2 g/2e3 times a day -LVFX, intravenous drip, 500 mg/once a day (2) Cases of late-onset hospital-acquired pneumonia or ventilator-associated pneumonia in which the risk of resistant bacteria is high An antimicrobial drug with anti-pseudomonal activity that targets non-glucose-fermentative gram-negative rod should be administered [50, 51, 68] -To treat polymicrobial infection, the administration of an antimicrobial drug with an activity against obligate anaerobe is not always necessary [67, 70] . -SBT/ABPC, intravenous drip, 3 g/3e4 times a day -CTRX, intravenous drip, 2 g/once a day or 1 g/twice a day -CTX, intravenous drip, 1e2 g/2e3 times a day -LVFX, intravenous drip, 500 mg/once a day (2) Late-onset hospital-acquired pneumonia or cases in which there is a risk of multi-drug-resistant bacteria In addition to the above pathogens, the involvement of non-glucose-fermentative gram negative bacteria or ESBLproducing enteric bacteria must be considered. For the treatment of immunodeficiency-/blood disease-related pneumonia in children, antimicrobial drug therapy should also be basically selected, considering causative microorganisms.
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         id = cord-284648-yznlgzir
     author = Varanko, Anastasia
      title = Recent trends in protein and peptide-based biomaterials for advanced drug delivery
       date = 2020-08-29
      pages = 
  extension = .txt
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      words = 33501
  sentences = 1732
     flesch = 42
    summary = Albumin is the most abundant protein in human plasma and has a set of properties that make it a unique molecular carrier for drugs: (i) it is a natural physiological carrier of native ligands and nutrients; (ii) it bypasses systemic clearance and degradation by the body's own innate mechanisms, so that it has an exceptionally long half-life of 19 days in humans, and similarly long half-lives in most animal species [123] [124] [125] [126] ; (iii) it preferentially accumulates at sites of vascular leakiness; (iv) it is highly internalized and metabolized by rapidly growing, nutrient-starved cancer cells; and (v) it is biodegradable and has no known systemic toxicity. Other notable examples of albumin-based delivery systems involve the genetic fusion of ABD to various therapeutic proteins including affibodies [165, 166] , human soluble complement receptor type 1 [167] , single chain antibody-drug conjugates [168] , insulin-like growth factor II [169] , immunotoxins [170] , and respiratory syncytial virus subgroup A (RSV-A) G protein (G2Na) [171] .
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         id = cord-303555-mwu72q7w
     author = Dent, Paul
      title = Cell Signaling and Translational Developmental Therapeutics
       date = 2020-10-06
      pages = 
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      words = 8877
  sentences = 556
     flesch = 49
    summary = Thus, by the mid-to late-1980s a large body of literature existed which argued that signal transduction pathways consisted of a receptor linked to a large GTP-binding protein which in turn regulated an enzyme that generated "second messengers;" the second messengers would then diffuse throughout the cytosol activating cellular processes, predominantly for metabolism. For the EGFR and other subsequently discovered membrane associated tyrosine kinases, e.g. the non-receptor SCR family and the fibroblast growth factor receptor (FGFR) family, understanding how these enzymes signaled into the cell again initially rested on studies using traditional biochemical methods. [71] [72] [73] [74] [75] [76] Contemporaneously with these studies, researchers were determining how receptor tyrosine kinases regulated RAS family small GTP binding proteins, and other groups determining how RAS proteins signaled downstream off the plasma membrane and into the cytosol.
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         id = cord-297010-imciixde
     author = Babayeva, Mariana
      title = Repurposing Drugs for COVID-19: Pharmacokinetics and Pharmacogenomics of Chloroquine and Hydroxychloroquine
       date = 2020-10-23
      pages = 
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      words = 7080
  sentences = 519
     flesch = 48
    summary = 81 Similar doses of the two drugs produced 11-fold variations in the blood concentrations in patients with rheumatoid arthritis 47, 63, 82, 83 and in healthy volunteers, 52, 64 suggesting different extend of metabolism among individuals. Determination of CYP3A, CYP2C8 and CYP2D6 polymorphism and, therefore, activity is important to establish safe and efficient dosing of chloroquine and hydroxychloroquine for treatment of COVID-19 patients. 125 Overall, the results suggest that CYP2C8, CYP2D6 and CYP3A genetic polymorphisms may influence chloroquine and hydroxychloroquine pharmacokinetics and COVID-19 patients treated with the same dose of CQ or HCQ may exhibit lack of efficacy or adverse reactions. Despite the evidence of the influence of genetic polymorphisms on the pharmacokinetics of chloroquine and hydroxychloroquine, no large pharmacogenomics studies have been conducted to provide guidance on the use, dosing, and duration of the therapy in COVID-19 patients.
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         id = cord-318048-6nvi63rq
     author = Arshad, Usman
      title = Prioritisation of Anti‐SARS‐Cov‐2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics
       date = 2020-05-21
      pages = 
  extension = .txt
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      words = 5663
  sentences = 288
     flesch = 46
    summary = An indication of the degree to which candidate drugs are expected to accumulate in lung (a presumed site of primary efficacy and for prevention of SARS-CoV-2 infection) was provided by calculation of unbound Accepted Article lung to plasma tissue partition coefficient (K p U lung ) according to the methodology of Rodgers and Rowland (20-22). All rights reserved Simulated exposure relative to reported anti-SARS-CoV-2 activity in lung and other tissues Lung K p U was simulated for all molecules for which the necessary physicochemical properties and in vitro drug binding information were available. The rank order of lung Cmax/EC 90 ratio was chloroquine > atazanavir (ritonavir boosted) > tipranavir (ritonavir boosted) > hydroxychloroquine > mefloquine > ivermectin > lopinavir (ritonavir boosted) > azithromycin > nitazoxanide > ritonavir > gilteritinib > amodiaquine > imatinib > oxprenolol (data excluded due to this analysis only being possible for 33 of the 56 drugs).
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         id = cord-314827-yqr7110e
     author = Attia, Yasmeen M.
      title = Successful stories of drug repurposing for cancer therapy in hepatocellular carcinoma
       date = 2020-09-04
      pages = 
  extension = .txt
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      words = 6483
  sentences = 300
     flesch = 28
    summary = Since HCC almost exclusively develops in patients with chronic liver diseases, injury of liver cells can promote the progression to HCC over a long period of time [11] driven by a number of cytokines and inflammatory mediators along with aberrant activity of several signaling pathways, as shown in Fig. 8 .1 (will be discussed later). Successful stories of drug repurposing for cancer therapy in hepatocellular carcinoma and HBV-and HCV-related proteins induction are among the mechanisms by which the Ras/ Raf/MAPK pathway can be activated toward HCC development [30] . Successful stories of drug repurposing for cancer therapy in hepatocellular carcinoma (genetically induced liver tumors and patientderived xenografts [PDXs]) for HCC to show significant reduction in the tumor growth after oral administration of NEN compared to niclosamide. Successful stories of drug repurposing for cancer therapy in hepatocellular carcinoma phenotypic events starting with induction of cell cycle arrest at G0/G12 phase accompanied with significant reduction in cell growth with elevated levels of KLF6/p21 protein content in HepG-2 cell line.
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         id = cord-298033-kzdp9edn
     author = Domingo, Esteban
      title = Quasispecies dynamics in disease prevention and control
       date = 2019-11-08
      pages = 
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      words = 16346
  sentences = 735
     flesch = 37
    summary = Quasispecies dynamics in disease prevention and control following statement will be obvious to the reader: "If a single mutation is able to confer resistance to an antiviral agent, and the mutation does not cause a significant selective disadvantage to the virus (fitness decrease) in the considered environment, a drug-resistant virus mutant will be present in most, if not all, virus populations" (Domingo, 1989) . The phenotypic barrier to drug resistance is equivalent to the fitness cost inflicted upon the virus by the mutations and corresponding amino acid substitution(s) required for resistance [Fitness cost is treated in Chapter 4 (Section 4.6) and in Chapter 7 (Section 7.4.2) in connection with the frequency of monoclonal antibody-or cytotoxic T-cell-escape mutants in viral populations]. For viruses that replicate in cell culture, it is possible to estimate the minimal viral population size needed to select a drug-resistant mutant which is generally positively correlated with the genetic barrier ( Fig. 8.5 ).
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         id = cord-006229-7yoilsho
     author = nan
      title = Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH)
       date = 2016-02-06
      pages = 
  extension = .txt
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      words = 133493
  sentences = 6804
     flesch = 42
    summary = It directly activates Protein Kinase A (PKA) or the Exchange protein directly activated by cAMP (Epac) which is a guanine exchange factor (GEF) for the small monomeric GTPase Rap. As Human umbilical vein endothelial cells (HUVEC) express both cAMP effectors (Epac1 and PKA), we investigated the role of cAMP-signaling using a spheroid based sprouting assay as an in vitro model for angiogenesis. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration Methods and Results: Here we demonstrate that dexamethasone treatment lowered S1P 1 mRNA and protein expression levels in rat mesangial cells measured by TaqMan® and Western blot analyses. The aim of this study was to investigate the relevance of IGFBP5 in cardiogenesis and cardiac remodeling and its role as a potential target for ameliorating stress-induced cardiac remodeling Methods and Results: We investigated the expression of Igfbp5 in murine cardiac tissue at different developmental stages by qPCR normalized to Tpt1 (Tumor Protein, Translationally-Controlled 1).
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         id = cord-299400-j18pj11d
     author = Norinder, Ulf
      title = Existing highly accumulating lysosomotropic drugs with potential for repurposing to target COVID-19
       date = 2020-07-30
      pages = 
  extension = .txt
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      words = 5310
  sentences = 251
     flesch = 42
    summary = We propose that the antiviral activity of (hydroxy)chloroquine and azithromycin is shared among all strong lysosomotropic drugs and is a consequence of their extremely high accumulation in cells and membranes, and subsequently of all the processes affected by this pharmacokinetic property. Among listed drugs with antiviral effects, the CADs include: psychoactive drugs (chlorpromazine, fluoxetine, clomipramine); antiarrhythmics (amiodarone); antimalarials (chloroquine, hydroxychloroquine, amodiaquine, mefloquine, quinacrine); channel blockers (amiodarone, verapamil, manidipine); antibacterial (azithromycin); estrogen receptor modulators (tamoxifen, raloxifene, toremifene); two antivirals, the only ones known to utilize CADs mechanism of J o u r n a l P r e -p r o o f antiviral action via the inhibition of endosomal pathway (arbidol (umifenovir) and tilorone (with additional activity of interferon induction)) (Boriskin et al., 2008 , Ekins et al., 2018 .
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         id = cord-317993-012hx4kc
     author = Movia, Dania
      title = Preclinical Development of Orally Inhaled Drugs (OIDs)—Are Animal Models Predictive or Shall We Move Towards In Vitro Non-Animal Models?
       date = 2020-07-24
      pages = 
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      words = 6885
  sentences = 369
     flesch = 42
    summary = SIMPLE SUMMARY: This commentary focuses on the methods currently available to test the efficacy and safety of new orally inhaled drugs for the treatment of uncurable respiratory diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis or lung cancer, prior to entering human experimentation. Inhalation is the preferred administration method for treating respiratory diseases [13] , as: (i) it delivers the drug directly at the site of action, resulting in a rapid therapeutic onset with considerably lower drug doses, (ii) it is painless and minimally invasive thus improving patients' compliance, and (iii) it avoids first-pass metabolism, providing optimal pharmacokinetic conditions for drug absorption and reducing systemic side effects [14] [15] [16] . In the context of OID preclinical testing, lung organoids can be used for modeling respiratory diseases and, therefore, as a platform for screening the efficacy of inhalation therapies [115, 116] .
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         id = cord-299911-v95pf3eg
     author = El-Ghiaty, Mahmoud A.
      title = Cytochrome P450-mediated drug interactions in COVID-19 patients: current findings and possible mechanisms
       date = 2020-06-26
      pages = 
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      words = 5319
  sentences = 272
     flesch = 37
    summary = Based on the conclusions drawn from the currently rapidly evolving knowledge about COVID-19, our hypothesis is built on the potential modulation of CYPs activity by the inflammatory environment provoked by SARS-CoV-2 infection, as well as the pathologic involvement of the liver which harbors the majority of the drug metabolizing enzymes (DMEs). Systemic inflammation and immune response represent a substantial element in many acute and chronic diseases which is strongly implicated in altering drug pharmacokinetics through, mainly, modulating the expression and activity of DMEs. As a main contributor to the metabolic biotransformation of most drugs, CYPs are widely involved in such disease-drug interactions [19] . For decades, IL-6 has been recognized as the major inflammatory element that provokes a significant repressive effect on the expression and activity of different CYPs. Human recombinant interleukin 6 (rhIL-6) has shown concentration-dependent blocking of phenobarbital-mediated induction of CYP2B1/2 mRNA and activity in rat hepatocytes [48] .
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         id = cord-308994-4nljzm8a
     author = Tang, Zhongmin
      title = Insights from nanotechnology in COVID-19 treatment
       date = 2020-11-04
      pages = 
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      words = 3239
  sentences = 177
     flesch = 36
    summary = We focus specifically on SARS-CoV-2 and the detailed role that nanotechnology can play in addressing this pandemic, including i) using FDA-approved nanomaterials for drug/vaccine delivery, including further exploration of the inhalation pathway; ii) introducing promising nanomaterials currently in clinical trials for drug/vaccine delivery; iii) designing novel biocompatible nanomaterials to combat the virus via interfering in its life cycle; and iv) promoting the utilization of nanomaterials in pneumonia treatment. To summarize, the advantages of nanotechnology in antiviral research include the following: 1) promotes the delivery of water-insoluble drugs; [39] 2) enhances the circulation time of drugs in vivo; [40] 3) achieves co-delivery of drugs; [40] 4) improves drug utilization efficiency and reduce side effects through targeting antibody modification; [41] 5) protects DNA and mRNA vaccines, overcoming bottlenecks for in vivo applications; [42] and 6) the physicochemical properties of nanomaterials can also be employed directly against viruses.
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         id = cord-326922-bajpr5a2
     author = Watson, C. James
      title = Pharmaceutical Compounding: a History, Regulatory Overview, and Systematic Review of Compounding Errors
       date = 2020-11-02
      pages = 
  extension = .txt
       mime = text/plain
      words = 7095
  sentences = 417
     flesch = 38
    summary = In the modern-day United States (US), medications are by-inlarge manufactured in commercial facilities, and this production is regulated and overseen by the US Food and Drug Administration (FDA). Furthermore, a new form of large-scale compounding has become commonplace, whereby pharmacies produce bulk volumes of medications which are not available commercially, and broadly distribute them to healthcare practices and individual patients. Patient harm caused by compounded medications has been the focus of media, medical, and legislative attention in recent years, especially following a multistate, multi-fatality outbreak of fungal meningitis caused by contaminated steroid injections compounded at a pharmacy in Framingham, MA [2, 3, 5, 6] . We categorized errors under the conceptual framework described by Sarah Sellers, PharmD, MPH, former board member for the FDA's Advisory Committee on Pharmacy Compounding, in testimony to the US Senate Committee on Health, Education, Labor, and Pensions, namely, that "suprapotency," "subpotency," and "contamination" are the primary risks associated with pharmaceutical compounding [59] .
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         id = cord-315918-12rbbe8c
     author = Mukherjee, Pulok K.
      title = Antiviral Evaluation of Herbal Drugs
       date = 2019-06-21
      pages = 
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      words = 12776
  sentences = 660
     flesch = 49
    summary = To test the inhibitory activity of a new antiviral agent, it is first necessary to select the host cell system(s) in which the virus replication can be measured. (d) Assay systems based on the measurement of specialized functions and viral products; a number of viruses do not produce plaques nor do they cause CPE readily, but they may be quantified by certain specialized functions based on their unique properties, for example, hemagglutination and hemadsorption tests used to study the antiviral activity against myxoviruses and ELISA, used to determine the extent of virus replication and, thus, obtain a measure of the inhibitory effect of various antiviral agents on virus replication, etc. On the other hand, the antiviral activity is determined by comparing the virus titers of infected cells, which have been cultured with a maintenance medium containing plant extracts or test substances and a maintenance medium without test material (Colegate and Molyneux, 1993) .
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         id = cord-316792-89f8g0m8
     author = Herzig, Volker
      title = Animal toxins — Nature’s evolutionary-refined toolkit for basic research and drug discovery
       date = 2020-06-12
      pages = 
  extension = .txt
       mime = text/plain
      words = 12747
  sentences = 631
     flesch = 42
    summary = Over the course of evolution, toxins with exceptional specificity and high potency for their intended molecular targets have prevailed, making venoms an invaluable and almost inexhaustible source of bioactive molecules, some of which have found use as pharmacological tools, human therapeutics, and bioinsecticides. Current biomedically-focused research on venoms is directed towards their use in delineating the physiological role of toxin molecular targets such as ion channels and receptors, studying or treating human diseases, targeting vectors of human diseases, and treating microbial and parasitic infections. Since many venoms and toxins exert these biological effects through actions on cell membranes, receptors and ion channels, high-throughput techniques assessing changes in cellular signalling have proven particularly insightful. Spider-venom peptides have been crucial for uncovering the key role of ASICs in stroke-induced brain damage, and validating these channels as a target for neuroprotective drugs [134] [135] [136] [137] .
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         id = cord-316029-z708c3ex
     author = Brunsdon, Priya
      title = Clinical Pharmacology Considerations for Developing Small‐Molecule Treatments for COVID‐19
       date = 2020-07-12
      pages = 
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      words = 4964
  sentences = 264
     flesch = 36
    summary = This review will offer key clinical pharmacology considerations for developing small molecules for the treatment of COVID-19 based on the major disease complications that impact drug absorption, distribution, metabolism, and elimination (ADME). Of major concern is sepsis, defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection." 12 In 1 study, septic shock, which is distinguished by persistent hypotension, elevated serum lactate levels, and increased mortality, was a complication in about 6% of severely ill COVID-19 patients. For water-soluble investigational therapies that are intended for administration in the severely ill COVID-19 population, thought should be given to targeting serum drug concentrations and the drug's exposure-response profile when determining if increased doses would be beneficial for patients receiving intravenous fluids. 21 The clinical impact of these potential changes in free drug fractions on investigational therapies that are highly proteinbound is an important consideration when empirically selecting doses for critically ill COVID-19 patients.
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         id = cord-309871-y17puao2
     author = Scherrmann, JM.
      title = Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy
       date = 2020-06-12
      pages = 
  extension = .txt
       mime = text/plain
      words = 3905
  sentences = 189
     flesch = 33
    summary = title: Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy The first one is related to the inverted influx transport of ABCB1, meaning that the azithromycin molecules, in addition to their passive diffusional uptake, are actively captured and trapped inside the vesicles, even if the vesicular intraluminal pH increases and the percentage of protonic drug molecules decreases enabling the backward diffusion of neutral species to the cytosol (Fig. 1) . To sum up, the intracellular ABCB1 could represent a potent target for enhancing the antiviral and antiinflammatory activities of the aminoquinolines when lysosomotropic ABCB1 substrates like azithromycin or ciprofloxacin are combined. In conclusion, we hypothesize that the intracellular ABCB1 may serve as a possible new target for improving the effects of the aminoquinolines when co-administered with a lysosomotropic drug, such as azithromycin or ciprofloxacin in COVID-19 chemotherapy.
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         id = cord-322885-ob5euspo
     author = Durdagi, Serdar
      title = Near-Physiological-Temperature Serial Femtosecond X-ray Crystallography Reveals Novel Conformations of SARS-CoV-2 Main Protease Active Site for Improved Drug Repurposing
       date = 2020-09-09
      pages = 
  extension = .txt
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      words = 10818
  sentences = 656
     flesch = 54
    summary = One Sentence Summary Radiation-damage-free high-resolution SARS-CoV-2 main protease SFX structures obtained at near-physiological-temperature offer invaluable information for immediate drug-repurposing studies for the treatment of COVID19. Radiation-damage-free SFX method which enables obtaining the novel high-resolution ambient-temperature structures of the binding pocket of Mpro provides an unprecedented opportunity for identification of highly effective inhibitors for drug repurposing by using a hybrid approach that combines structural and in silico methods. We determined two radiation-damage-free SFX crystal structures of SARS-CoV-2 Mpro in two crystal forms at 1.9 Å and 2.1 Å resolutions with the following PDB IDs: 7CWB and 7CWC, respectively (Fig. 1A, B) (Supplementary Table 1&2 The diffraction data collected remotely at the MFX instrument of the LCLS at SLAC National Laboratory, Menlo Park, CA (Sierra et al., They reveal novel active site residue conformations and dynamics at atomic level, revealing several differences compared to the prior ambient-temperature structure of SARS-CoV-2 Mpro that was obtained at a home X-ray source (Fig. 1A, B ).
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         id = cord-311730-189vax2m
     author = Becker, Richard C.
      title = Covid-19 treatment update: follow the scientific evidence
       date = 2020-04-27
      pages = 
  extension = .txt
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      words = 4514
  sentences = 222
     flesch = 40
    summary = The SNS exists under the authority of the United States Department of Health and Human Services (HHS) and accepted 30 million doses of hydroxychloroquine sulfate donated by Sandoz™, the Novartis™ generics and biosimilars division, and one million doses of chloroquine phosphate donated by Bayer Pharmaceuticals™ for potential use in treating patients who were hospitalized with COVID-19 or for use in clinical trials. The adverse effects associated with taking hydroxychloroquine are similar to those observed with chloroquine and include nausea, vomiting, diarrhea, AV conduction defects, a prolonged QTc interval with torsades de pointe ventricular tachycardia, hypokalemia, hypotension and circulatory collapse. Similarly, patients with Covid-19 for whom a clinician believes that either chloroquine or hydroxychloroquine is indicated must receive information, preferably in the form of a fact sheet that clearly summarized the dose, duration of treatment, potential risks, side-effects and drug-drug interactions.
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         id = cord-321741-aq76s37x
     author = Andersen, Petter I.
      title = Discovery and development of safe-in-man broad-spectrum antiviral agents
       date = 2020-04-30
      pages = 
  extension = .txt
       mime = text/plain
      words = 5432
  sentences = 308
     flesch = 41
    summary = Although the concept of BSAAs has been around for almost 50 years, the field received a new impetus with recent outbreaks of Ebola, Zika, Dengue, influenza and other viral infections, the discovery of novel host-directed agents, as well as development of drug repositioning methodology. The discovery of novel activities of BSAAs starts with exposing cells to the candidate antiviral agent at different concentrations and infecting the cells with a virus or mock. Given that emetine also inhibits ZIKV, EBOV, RABV, CMV, HCoV-OC43 and HIV-1 infections (Chaves Valadao et al., 2015; MacGibeny et al., 2018; Mukhopadhyay et al., 2016; Shen et al., 2019; Yang et al., 2018) , and that it is an FDA-approved anti-protozoal drug, it may represent a promising safe-in-man BSAA candidate. Thereby, novel antiviral activities of BSAAs should be further validated in primary human cells using different viral strains (including wild-type viruses), different viral loads, different times of compound addition, different endpoint measurements and compound concentration range.
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         id = cord-325315-m3do6t1j
     author = Rossi, Carlo Maria
      title = A case report of toxic epidermal necrolysis (TEN) in a patient with COVID-19 treated with hydroxychloroquine: are these two partners in crime?
       date = 2020-10-06
      pages = 
  extension = .txt
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      words = 2540
  sentences = 152
     flesch = 45
    summary = Given the activation of the immune system syndrome induced by the virus and the widespread off-label use of this drug, we suggest a careful monitoring of skin and mucous membranes in all COVID-19 positive patients treated with hydroxychloroquine in order to early detect early signs of toxicities. Another salient aspect of the case is the favorable evolution of the patient given that this type of SCAR is typically associated with a bad prognosis [35] [36] [37] , even more so because the patient displayed all the negative typical prognostic factors also for COVID-19 [38] [39] [40] [41] , indeed the calculation of the severity-of-illness score for toxic epidermal necrolysis (SCORTEN) in our patient led to an estimated mortality rate of 58.3% (CI 36,6 -77,59) ( Table 2 ) [42, 43] .
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         id = cord-321657-2s1npse5
     author = Du, Sean Quan
      title = Mathematical modeling of interaction between innate and adaptive immune responses in COVID‐19 and implications for viral pathogenesis
       date = 2020-05-13
      pages = 
  extension = .txt
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      words = 6461
  sentences = 294
     flesch = 59
    summary = 4 In this paper, we used mathematical modeling to investigate the dynamics of the viral infection/replication inside a human host, in particular, the influenza and the SARS-CoV-2 virus, as well as the interactions of target cells with the innate and AIRs. Our model suggests that most of the differences between the two types of infections can potentially be attributed to the timing mismatch between the two immune responses. More specifically, influenza is a very acute infection; all vulnerable cells are completely depleted and viruses are more or less cleared by the innate immune response, before the adaptive immune response (AIR), which has a transient nature, reaches a significant level. We proposed an immune-suppressing treatment based on the leanings of our modeling study, which is to apply immunosuppressive drugs during the early phase of infection to reduce the AIRs to a level low enough not to interfere with the innate immune response.
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         id = cord-304506-6el2ryl8
     author = Watkins, Laura C.
      title = Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics
       date = 2020-09-16
      pages = 
  extension = .txt
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      words = 6140
  sentences = 277
     flesch = 45
    summary = In this work, we examine the hypothesis that these drugs act primarily as mechanism-based inhibitors by comparing hydrated excess proton stabilization during proton transport in M2 with the interactions revealed in the crystal structures, using the Multiscale Reactive Molecular Dynamics (MS-RMD) methodology. Along with an earlier qualitative MD simulation study that guided the design of the spiro-adamantyl amine inhibitors, 44 the crystallographic analysis provided potential insights into the mechanism of inhibition, suggesting that the backbone carbonyls of pore-lining residues act as "physiochemical chameleons", able to engage in both hydrophobic and hydrophilic interactions, and that the drug is tilted off the channel's axis and interacts with waters in the Ala30 layer. Most recently, we further analyzed the MS-RMD simulations to explore the detailed interactions between the hydrated excess proton and the channel and found that the proton dynamically, as a function of its position, alters several properties of the protein and pore waters, including the hydrogen bonding network and the protein structure.
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         id = cord-334170-85x5vmyi
     author = Masoudi-Sobhanzadeh, Yosef
      title = Synthetic repurposing of drugs against hypertension: a datamining method based on association rules and a novel discrete algorithm
       date = 2020-07-16
      pages = 
  extension = .txt
       mime = text/plain
      words = 6507
  sentences = 383
     flesch = 56
    summary = title: Synthetic repurposing of drugs against hypertension: a datamining method based on association rules and a novel discrete algorithm RESULTS: A novel two-step data mining method, which is based on the If-Then association rules as well as a novel discrete optimization algorithm, was introduced and applied to the synthetic repurposing of drugs for HT. CONCLUSION: Since the proposed synthetic method uses medications in small dosages, it might revive some failed drug development projects and put forward a suitable plan for treating different diseases such as COVID-19 and HT. Based on the obtained results, it can be concluded that Trader (the newly introduced algorithm) is more efficient than the other state-of-the-art algorithms and proposes some better synthetic drug lists to treat HT. To discover the hidden applications of the existing drugs, a drug repositioning method, which is based on the newly introduced discrete optimization algorithm (Trader) and If-Then association rules, was proposed.
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         id = cord-324660-w81jgw7p
     author = Guharoy, Roy
      title = Medication Shortages: A Matter of National Security—Time for Action
       date = 2020-08-01
      pages = 
  extension = .txt
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      words = 1105
  sentences = 56
     flesch = 47
    summary = To the Editor: As noted by Choo and Rajkumar 1 in the June 2020 issue of Mayo Clinic Proceedings, the COVID-19 (coronavirus disease 19) pandemic has exposed extreme vulnerabilities in our nation's drug supply chain. d Create a national database for tracking of essential drug supplies and use predictive analytics to identify surge, production problems, and future shortages. 1 As supply chain management leaders at Mayo Clinic, we appreciate the attention these authors draw towards the issue of drug shortages and drug costs. 5 Because of the high use of vasopressin in critically ill COVID-19 patients and the greater than 6000% price increase that has occurred after completing the Unapproved Drugs Initiative process, vasopressin will likely become a top 10 drug expense within the hospital sector by the end of 2020. The FDA Unapproved Drugs Initiative: an observational study of the consequences for drug prices and shortages in the United States
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         id = cord-336554-n8n5ii5k
     author = Singh, Thakur Uttam
      title = Drug repurposing approach to fight COVID-19
       date = 2020-09-05
      pages = 
  extension = .txt
       mime = text/plain
      words = 13032
  sentences = 690
     flesch = 44
    summary = Number of drugs such as remdesivir, favipiravir, ribavirin, lopinavir, ritonavir, darunavir, arbidol, chloroquine, hydroxychloroquine, tocilizumab and interferons have shown inhibitory effects against the SARS-CoV2 in-vitro as well as in clinical conditions. Outbreaks of novel emerging infections such as coronavirus disease 2019 (COVID19) have unique challenges in front of the health professionals to select appropriate therapeutics/pharmacological treatments in the clinical setup with very little time available for the new drug discovery [3] . Currently, with the lack of effective agents against SARS-CoV2 as well as public-health emergency, WHO has identified some therapies which doctors and researchers believe are the most promising, such as a combination of two HIV drugs (lopinavir and ritonavir), anti-malarial drugs (chloroquine and hydroxychloroquine), and an experimental antiviral compound remdesivir. Ribavirin at a dose rate of 500 mg 2-3 times/day in combination with other drugs such as lopinavir/ritonavir or interferon (IFN)-α through intravenous route for not more than 10 days made the SARS-CoV2 infected patients more resistant to respiratory distress syndrome as well as death [41] .
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         id = cord-334881-x9nxxled
     author = Di Lorenzo, Giuseppe
      title = COVID 19 therapies and anti-cancer drugs: A systematic review of recent literature
       date = 2020-05-21
      pages = 
  extension = .txt
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      words = 3248
  sentences = 186
     flesch = 45
    summary = BACKGROUND: It is reasonable to think that cancer patients undergoing chemotherapy, targeted therapy or immunotherapy could have a more aggressive course if positive for Coronavirus disease CoV-2 (COVID19). METHODS: We conducted a literature review on https://www.ncbi.nlm.nih.gov/pubmed/, https://scholar.google.com, www.arxiv.org, www.biorxiv.org, of all articles published using the keywords COVID-19 therapy or treatment and cancer until May 2, 2020. Sarilumab is an interleukin-6 (IL-6) receptor antagonist indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs) (53). AIFA has licensed a randomized phase 2 trial to evaluate the efficacy, safety and tolerability of J o u r n a l P r e -p r o o f baricitinib in addition to the usual treatment in patients with pneumonia in COVID-19 (Barcivid study) (74).
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         id = cord-353524-3w970ycx
     author = Dömling, Alexander
      title = Chemistry and Biology of SARS-CoV-2
       date = 2020-05-22
      pages = 
  extension = .txt
       mime = text/plain
      words = 3942
  sentences = 237
     flesch = 52
    summary = Given that SARS-CoV-2 and SARS-CoV share very high identical sequence in their 3CLpro, these HIV protease inhibitors are currently again repurposed for the treatment of COVID-19 (Chinese Clinical Trial Registry: ChiCTR2000029539). 30, 31 The interplay of the ACE receptor in cardiovascular diseases (with the well-known drug class of ACE inhibitors) and as the docking point for SARS-CoV-2 cellular infection is a current point of intense debate and research. For example, the crystal structure of SARS-CoV-2 N protein RNA-binding domain was just published and will give structural insight as a potential drug target. Potential broad spectrum inhibitors of the coronavirus 3CLpro: A virtual screening and structure-based drug design study Severe acute respiratory syndrome coronavirus papain-like novel protease inhibitors: design, synthesis, protein-ligand X-ray structure and biological evaluation Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites
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         id = cord-354180-6esn3t2b
     author = Tyndall, Mark
      title = Safer opioid distribution in response to the COVID-19 pandemic
       date = 2020-07-27
      pages = 
  extension = .txt
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      words = 4223
  sentences = 221
     flesch = 57
    summary = The arrival of the COVID-19 pandemic comes at time when North America is in the midst of a protracted overdose epidemic caused by a toxic illegal drug supply. Overdose deaths are likely to rise when people are isolated, social support programs are cut back, and the illicit drug supply is further compromised. Safer opioid distribution in response to a toxic street drug supply is a pragmatic and effective way to reduce overdose deaths. Even if emergency housing can be found and mitigation strategies to reduce COVID-19 transmission are put in place, the need to access an illegal drug supply makes staying in place extremely unlikely (Bodkin et al., 2020) . A waning tolerance to opioids means that the first exposure to street drugs can be deadly and it is critical that proper discharge planning and supports are in place (Bukten et al.,2017) Many people who use drugs rely on public services for medical care, harm reduction supplies, street outreach, and food distribution.
      cache = ./cache/cord-354180-6esn3t2b.txt
       txt  = ./txt/cord-354180-6esn3t2b.txt
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         id = cord-348245-pf5mlzrw
     author = Moura-Neto, José A.
      title = Position statement from the Brazilian Society of Nephrology regarding chloroquine and hydroxychloroquine drug dose adjustment according to renal function
       date = 2020-08-26
      pages = 
  extension = .txt
       mime = text/plain
      words = 962
  sentences = 57
     flesch = 47
    summary = On the first day of April 2020, Informative Note nº 6/2020-DAF/SCTIE/MS was published, establishing that the Brazilian Ministry of Health (MS) would make the medications available for use, in confirmed cases and at medical criteria, chloroquine and hydroxychloroquine as adjunctive therapy in the treatment of severe forms in hospitalized patients, without other supportive measures being neglected in their favor 1 . On April 6, the MS published "Guidelines for the diagnosis and treatment of Covid-19", in which it also instructed on the use of chloroquine and hydroxychloroquine as adjuvant therapy in severe forms of the disease, in confirmed cases and upon medical discretion 2 . Given the above and the associated risks, the Brazilian Society of Nephrology advises its associate doctors to prescribe one of these drugs according to the recommendations established by CFM and MS, which recommend a 50% reduction in the recommended dose of chloroquine and hydroxychloroquine in patients with glomerular filtration rate <10 mL/min/1.72 m 2 , in dialysis or conservative treatment.
      cache = ./cache/cord-348245-pf5mlzrw.txt
       txt  = ./txt/cord-348245-pf5mlzrw.txt
=== reduce.pl bib ===
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         id = cord-330380-wnbyy1gk
     author = Liu, Tingting
      title = Applying high-performance computing in drug discovery and molecular simulation
       date = 2016-01-11
      pages = 
  extension = .txt
       mime = text/plain
      words = 8570
  sentences = 411
     flesch = 38
    summary = With the improvement of high-performance technologies, HPC and supercomputers are being applied to an increasing number of emerging fields including deep learning, big data mining, computational finance, and precision medicine, with the expectation that it will accelerate innovation. A series of CDDD approaches based on the 3D structures of biological macromolecules (e.g. proteins and nucleic acids), such as the highthroughput virtual screening method, have greatly improved the efficiency of drug discovery. This review mainly focuses on the application of HPC to the field of drug discovery and molecular simulation at CAS in recent years, including several cases involving virtual screening (molecular docking), MD simulation, and protein folding. Taken together, our study not only demonstrated that the α-helix/β-sheet intermediate structures revealed by the aforementioned simulations could be used as a binding target for inhibitor design, but also provided new insights into the molecular events involved in the conformational transition of Aβ peptides in fibrillogenesis.
      cache = ./cache/cord-330380-wnbyy1gk.txt
       txt  = ./txt/cord-330380-wnbyy1gk.txt
=== reduce.pl bib ===
         id = cord-347579-aqgauumt
     author = Csete, Joanne
      title = United States drug courts and opioid agonist therapy: Missing the target of overdose reduction
       date = 2020-06-09
      pages = 
  extension = .txt
       mime = text/plain
      words = 4141
  sentences = 173
     flesch = 55
    summary = • Drug courts overall have had limited success in improving access to OUD treatment and other health and social services needed to achieve significant reduction in overdose death. • Drug courts overall have had limited success in improving access to OUD treatment and other health and social services needed to achieve significant reduction in overdose death. In the face of such a crisis, it might be supposed that policy-makers would do everything possible to reduce overdose risk, including improving access to the several authorized forms of proven treatment for opioid use disorder (OUD). A 2013 national survey of drug courts found that although virtually all of the courts reported having participants with opioid use disorders, only 47% offered agonist therapy as an option for court-supervised treatment (Matusow, Dickman, Rich, Fong, Dumont, Hardin et al., 2013) .
      cache = ./cache/cord-347579-aqgauumt.txt
       txt  = ./txt/cord-347579-aqgauumt.txt
=== reduce.pl bib ===
=== reduce.pl bib ===
         id = cord-322915-zrjx31ev
     author = Demain, Arnold L
      title = Microbial drug discovery: 80 years of progress
       date = 2009-01-09
      pages = 
  extension = .txt
       mime = text/plain
      words = 11246
  sentences = 688
     flesch = 40
    summary = Evidence of the importance of natural products in the discovery of leads for the development of drugs for the treatment of human diseases is provided by the fact that close to half of the best selling pharmaceuticals in 1991 were either natural products or their derivatives. In addition to the antibiotic-resistance problem, new families of anti-infective compounds are needed to enter the marketplace at regular intervals to tackle the new diseases caused by evolving pathogens. 28 Among the novel class of antimicrobial agents used in treating resistance to Gram-positive infections, we can also mention the cyclic lipopeptide antibiotic daptomycin produced by Streptomyces roseosporus. 44 Other applications include antitumor drugs, enzyme inhibitors, gastrointestinal motor stimulator agents, hypocholesterolemic drugs, ruminant growth stimulants, insecticides, herbicides, coccidiostats, antiparasitics vs coccidia, helminths and other pharmacological activities. Considering that animal health research and the development of new anti-infective product discovery have decreased, the discovery of new antibiotics has decreased over the past 15 years, with few new drug approvals.
      cache = ./cache/cord-322915-zrjx31ev.txt
       txt  = ./txt/cord-322915-zrjx31ev.txt
=== reduce.pl bib ===
         id = cord-329318-eo8auo1f
     author = Gusarov, Sergey
      title = COSMO-RS-Based Descriptors for the Machine Learning-Enabled Screening of Nucleotide Analogue Drugs against SARS-CoV-2
       date = 2020-10-26
      pages = 
  extension = .txt
       mime = text/plain
      words = 3971
  sentences = 217
     flesch = 46
    summary = [Image: see text] Chemical similarity-based approaches employed to repurpose or develop new treatments for emerging diseases, such as COVID-19, correlates molecular structure-based descriptors of drugs with those of a physiological counterpart or clinical phenotype. In this study, we propose a novel set of drug screening descriptors based on COSMO-RS σ-profiles, augmented by dipole moment and induced charge of the phosphorus atom, to evaluate the chemical similarity of the drugs with nucleotides, as RNA replication transcription initiation activators. A novel set of descriptors based on COSMO-RS σ-profiles and chemical thermodynamics is proposed and evaluated using PCA for the initial screening of a series of nucleotides and nucleotide-analog RdRp replication inhibitor drugs to help accelerate the discovery of COVID-19 treatments. The PCA results show that the novel σ-profile-based descriptor set I clearly correlates the leading COVID-19 drugs remdesivir and EIDD-2801 in monophosphate forms and highlights weaker correlations with drugs that have been reported to exhibit anti-SARS-CoV-2 activity.
      cache = ./cache/cord-329318-eo8auo1f.txt
       txt  = ./txt/cord-329318-eo8auo1f.txt
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         id = cord-334511-lx9608vy
     author = Emwas, Abdul-Hamid
      title = NMR as a “Gold Standard” Method in Drug Design and Discovery
       date = 2020-10-09
      pages = 
  extension = .txt
       mime = text/plain
      words = 29224
  sentences = 1507
     flesch = 47
    summary = The nearly ubiquitous use of virtual screening is due to its efficiency in searching massive chemical databases in order to generate lead molecules [313] that inhibit protein-protein interactions [314] , and its ability to help identity ligand (drug) binding sites on the target of interest [310] to lend insight to the mechanisms of action for lead compounds [315, 316] . The nearly ubiquitous use of virtual screening is due to its efficiency in searching massive chemical databases in order to generate lead molecules [313] that inhibit protein-protein interactions [314] , and its ability to help identity ligand (drug) binding sites on the target of interest [310] to lend insight to the mechanisms of action for lead compounds [315, 316] . Clearly, combining virtual screening with NMR-based methods is advantageous in studying how ligands (drugs) bind and interact with targets (proteins) of interest. The interactions between targets (proteins) and ligands (small molecules) can be analyzed independently of the biological systems by using 'cell-based' NMR drug design approaches.
      cache = ./cache/cord-334511-lx9608vy.txt
       txt  = ./txt/cord-334511-lx9608vy.txt
=== reduce.pl bib ===
         id = cord-320172-qw47pf9r
     author = Greaves, Peter
      title = VII Digestive System 1
       date = 2000-12-31
      pages = 
  extension = .txt
       mime = text/plain
      words = 47375
  sentences = 2238
     flesch = 40
    summary = In common with other changes induced in the digestive tract of rats and cynomolgus monkeys by the administration of recombinant human epidermal growth factor, the tongue showed squamous epithelial hyperplasia characterised by a uniform increase in the thickness of the squamous epithelium in both species (Breider et al., 1996; Reindel et al., 1996) . Detailed study of hypertrophy, protein synthesis, and intracellular cAMP activity in the salivary glands of rats treated for 10 days with isoprenaline (isoproterenol), a series of β-adrenergic receptor agonists and the phosphodiesterase inhibitors, theophylline and caffeine, showed that similar effects occurred with all agents although differences in the degree of hypertrophy, the nature of pro-tein and glycoprotein synthesis and Golgi membrane enzyme activity were recorded (Wells and Humphreys-Beher, 1985) . Studies in the rat have shown that diffuse atrophy of the gastric glands characterised by a decrease in the number and size of parietal, chief and mucous cells occurs transiently following truncal vagotomy but histological features return to normal by about 1 month after surgery (Nakamura, 1985) .
      cache = ./cache/cord-320172-qw47pf9r.txt
       txt  = ./txt/cord-320172-qw47pf9r.txt
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         id = cord-353572-b4mdiont
     author = Zhou, Yadi
      title = Network-based Drug Repurposing for Human Coronavirus
       date = 2020-02-05
      pages = 
  extension = .txt
       mime = text/plain
      words = 6871
  sentences = 390
     flesch = 42
    summary = Using network proximity analyses of drug targets and known HCoV-host interactions in the human protein-protein interactome, we computationally identified 135 putative repurposable drugs for the potential prevention and treatment of HCoVs. In addition, we prioritized 16 potential anti-HCoV repurposable drugs (including melatonin, mercaptopurine, and sirolimus) that were further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations toward future clinical trials for HCoVs. Coronaviruses (CoVs) typically affect the respiratory tract of mammals, including humans, and lead to mild to severe respiratory tract infections [1] . These network proximity analyses offer putative repurposable candidates for potential prevention and treatment of HCoVs. To further validate the 135 repurposable drugs against HCoVs, we first performed gene set enrichment analysis (GSEA) using transcriptome data of MERS-CoV and SARS-CoV infected host cells (see Methods).
      cache = ./cache/cord-353572-b4mdiont.txt
       txt  = ./txt/cord-353572-b4mdiont.txt
=== reduce.pl bib ===
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         id = cord-347986-ds5hm731
     author = Lee, Paul J.
      title = Developing Infectious Disease Strategies for the Developing World
       date = 2007-01-26
      pages = 
  extension = .txt
       mime = text/plain
      words = 4102
  sentences = 193
     flesch = 48
    summary = The neuraminidase inhibitors, oseltamivir and zanamivir, have in vitro activities against the human H5N1 isolates; however, recent data suggest that higher doses for longer periods may be required to be effective. Human immunodeficiency virus (HIV), Ebola virus, hantavirus pulmonary syndrome, monkey pox and multidrug-resistant Mycobacterium tuberculosis (MDR-TB), Severe Acute Respiratory Syndrome (SARS) associated coronavirus and avian influenza are examples of emerging infections. Through a discussion of avian influenza and MDR-TB, primarily, we will demonstrate the magnitude of the problems of infectious diseases in the developing world and discuss approaches that can be taken to in an attempt to monitor and contain these new threats as they emerge. In fact, a recent Cochrane review covering appropriate studies to address the problem of treating latent tuberculosis infection in people exposed to MDR-TB found there were no randomized controlled trials in the database that have assessed the effectiveness of treatment [11] .
      cache = ./cache/cord-347986-ds5hm731.txt
       txt  = ./txt/cord-347986-ds5hm731.txt
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         id = cord-355971-99mhacqa
     author = Gougis, Paul
      title = Anticancer drugs and COVID-19 antiviral treatments in cancer patients: what can we safely use?
       date = 2020-06-10
      pages = 
  extension = .txt
       mime = text/plain
      words = 761
  sentences = 63
     flesch = 38
    summary = title: Anticancer drugs and COVID-19 antiviral treatments in cancer patients: what can we safely use? • More safety data is needed to treat COVID-19 symptomatic patients with anticancer drugs known to increase infections. • A ready-to-use table synthetize these pharmacokinetic and pharmacodynamic interactions between antiviral and anticancer drugs. 1 In any of these settings, clinical trials and incoming standard of care could lead to the prescription of antiviral drugs concomitant to non-immunosuppressive anticancer treatments. Favipiravir, an anti-EBOV drug, also a candidate for the COVID-19 treatment, is an inhibitor of CYP2C8, 3 and therefore may increase anticancer drug metabolized through this pathway, such as dabrafenib and enzalutamide. The table (part B) summarizes pharmacokinetic and pharmacodynamics interactions between some currently tested drugs against COVID-19 and anticancer drugs. Orange boxes are for anticancer drugs prolonging QT without known Torsade-de-Pointes risk and moderate risk for renal and liver toxicities.
      cache = ./cache/cord-355971-99mhacqa.txt
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         id = cord-349794-mhviub6e
     author = Le, Brian L.
      title = Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19
       date = 2020-10-23
      pages = 
  extension = .txt
       mime = text/plain
      words = 3810
  sentences = 216
     flesch = 43
    summary = We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available data. By infecting human adenocarcinomic alveolar basal epithelial cells with SARS-CoV-2 and comparing to controls, the authors generated a list of 120 differentially expressed genes. Here, we applied our existing computational drug repositioning pipeline to identify drug profiles with significantly reversed differential gene expression compared to predicted inhibitors (including one tested in Calu-3) were incubated with SARS-CoV-2 infected human embryonic kidney 293T cells overexpressing ACE2 (293T-ACE2) with viral replication determined using an immunofluorescence-based assay. In this study, we applied our drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available RNA-seq data ( Figure 1 ). Here, we used a transcriptomics-based drug repositioning pipeline to predict therapeutic drug hits for three different input SARS-CoV-2 signatures, each of which came from distinct human cell or tissue origins.
      cache = ./cache/cord-349794-mhviub6e.txt
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         id = cord-354445-lnvc7mmf
     author = Lichtenstein, David
      title = 4 Cleaning and Disinfecting Gastrointestinal Endoscopy Equipment
       date = 2019-12-31
      pages = 
  extension = .txt
       mime = text/plain
      words = 13656
  sentences = 833
     flesch = 39
    summary = Abstract Outbreaks of infection transmission due to contaminated flexible endoscopes have focused the attention of health care personnel, senior management, device manufacturers, and regulators on the need to improve the approach used to offer this valuable service. Salmonella is a serious primary pathogen, and Pseudomonas is ubiquitous in many water sources, and although both these pathogens have been associated most frequently with endoscopic transmission, they are both sensitive to multiple agents, including glutaraldehyde, and other HLDs. Transmission of bacterial pathogens from flexible endoscopes has been rare since the adoption of the current 2011 multisociety reprocessing guideline, 45, 160 with the exception of duodenoscope-related infections (discussed later). Society of Gastroenterology Nurses and Associates: Guideline for use of high level disinfectants & sterilants for reprocessing flexible gastrointestinal endoscopes Society of Gastroenterology Nurses and Associates: Guideline for use of high level disinfectants & sterilants for reprocessing flexible gastrointestinal endoscopes
      cache = ./cache/cord-354445-lnvc7mmf.txt
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         id = cord-342756-rgm9ffpk
     author = Senger, Mario Roberto
      title = COVID-19: molecular targets, drug repurposing and new avenues for drug discovery
       date = 2020-10-02
      pages = 
  extension = .txt
       mime = text/plain
      words = 16108
  sentences = 1024
     flesch = 51
    summary = Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. In the following topic, we will review SARS-CoV-2 structure and mechanism of infection in order to discuss molecular targets from the virus or its human host that are being considered for drug repurposing and perhaps future development of new drugs. (128) Its role as a functional receptor of SARS-CoV-2 S protein in host cells makes this protein a potential drug target to treat COVID-19. (138) TMPRSS2 has a major role in SARS-CoV-2 cell entry and replication, and thus represents an interesting therapeutic target since its inhibitors could potentially block virus infection in its initial stages. (199) A robust preclinical drug discovery pipeline comprising in vitro, and in vivo models of SARS-CoV-2 infection is particularly important to identify new antivirals for human COVID-19 treatment.
      cache = ./cache/cord-342756-rgm9ffpk.txt
       txt  = ./txt/cord-342756-rgm9ffpk.txt
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         id = cord-351185-3y3gou6v
     author = Buckles, Thomas C.
      title = Rapid exposure of macrophages to drugs resolves four classes of effects on the leading edge sensory pseudopod: Non-perturbing, adaptive, disruptive, and activating
       date = 2020-05-29
      pages = 
  extension = .txt
       mime = text/plain
      words = 10061
  sentences = 465
     flesch = 45
    summary = However, rapid drug addition to cultured macrophages revealed four distinct classes of effects on the leading edge pseudopod: (i) non-perturbing drug exposures yielded no detectable change in pseudopod morphology (acetylsalicylic acid, diclofenac); (ii) adaptive exposures yielded temporary collapse of the extended pseudopod and its signature PI(3,4,5)P(3) lipid signal followed by slow recovery of extended pseudopod morphology (ibuprofen, acetaminophen); (iii) disruptive exposures yielded long-term pseudopod collapse (Gö6976, wortmannin); and (iv) activating exposures yielded pseudopod expansion (PDGF). In contrast, ibuprofen and acetaminophen are classified as adaptive because rapid addition of either drug to polarized cells yields short-term collapse of the leading edge pseudopod and loss of the PIP 3 signal, followed by slow recovery. In contrast to the four therapeutic adaptive drugs, the two non-clinical control inhibitors wortmannin and Gö6976 are each known to directly inhibit key components of the leading edge positive feedback loop and rapid addition is observed herein to trigger long term collapse of the pseudopod with no detected recovery as previously observed [26, 30, [50] [51] [52] [53] [54] .
      cache = ./cache/cord-351185-3y3gou6v.txt
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         id = cord-350571-6tapkjb6
     author = nan
      title = 45th ESCP-NSF international symposium on clinical pharmacy: clinical pharmacy tackling inequalities and access to health care. Oslo, Norway, 5–7 October 2016
       date = 2017-01-10
      pages = 
  extension = .txt
       mime = text/plain
      words = 106013
  sentences = 6203
     flesch = 48
    summary = Possible solutions might be to use shared communication tools like Internet based communication programs and to introduce the patient as a participant at the IMRs. Please specify your abstract type: Research abstract Background and objective: International good pharmacy practice guidelines describe how pharmacists should counsel the patients about their medicines, offer additional services where needed, and intervene at drug related problems. Please specify your abstract type: Descriptive abstract (for projects) Background and objective: In order to improve the medication reconciliation and to implement training programs for the medical team in an associated to general hospital nursing (ASNH) home we measured the discrepancies between pharmacy registered treatments (PRT) and medical prescriptions (MP), and we analysed potentially inappropriate prescriptions according to ''American Geriatrics Society 2015 Beers Criteria'' and ''STOPP-START 2014 criteria.
      cache = ./cache/cord-350571-6tapkjb6.txt
       txt  = ./txt/cord-350571-6tapkjb6.txt
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Creating transaction
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===== Reducing keywords
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Creating transaction
Updating wrd table
===== Reducing urls
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Creating transaction
Updating url table
===== Reducing named entities
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cord-350571-6tapkjb6
Creating transaction
Updating ent table
===== Reducing parts of speech
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cord-334511-lx9608vy
cord-320172-qw47pf9r
cord-006229-7yoilsho
cord-350571-6tapkjb6
Creating transaction
Updating pos table
Building ./etc/reader.txt
cord-275828-c6d6nk7x
cord-350571-6tapkjb6
cord-284648-yznlgzir
cord-284648-yznlgzir
cord-032561-x3qbqy69
cord-264867-ezsy76mx
                number of items: 196
                   sum of words: 1,184,791
          average size in words: 12,604
      average readability score: 44

                          nouns: drug; patients; drugs; treatment; cells; study; cell; protein; disease; use; effects; virus; results; studies; data; delivery; therapy; activity; cancer; health; infection; time; development; proteins; system; effect; lung; analysis; acid; dose; risk; diseases; cases; type; model; inhibitors; number; target; patient; care; response; structure; years; receptor; compounds; role; research; information; approach; administration
                          verbs: used; shows; based; including; increase; induced; associated; developed; identify; providing; reported; found; bind; followed; treated; targeting; reduced; compared; caused; leads; related; made; improving; require; inhibited; suggests; observed; known; perform; considered; involving; took; resulted; occurring; demonstrated; contains; given; indicated; seen; produced; describes; evaluate; approved; predicting; presenting; obtained; needed; determines; affected; allow
                     adjectives: clinical; high; human; new; different; viral; therapeutic; potential; antiviral; specific; non; anti; many; molecular; several; low; respiratory; important; severe; first; effective; acute; pulmonary; oral; available; small; main; significant; higher; various; novel; active; inflammatory; possible; similar; large; common; adverse; multiple; single; recent; medical; major; chronic; positive; current; immune; structural; resistant; biological
                        adverbs: also; however; well; therefore; often; respectively; significantly; even; recently; highly; currently; furthermore; still; particularly; especially; usually; less; moreover; already; generally; previously; potentially; mainly; now; first; widely; commonly; relatively; frequently; finally; clinically; hence; rapidly; approximately; directly; together; additionally; rather; much; yet; far; alone; specifically; primarily; almost; thereby; least; later; prior; strongly
                       pronouns: it; we; their; its; they; our; them; i; your; he; his; us; itself; she; her; one; you; themselves; my; me; him; himself; ashcs; ns3/4a; mg; ours; em; ∕; yourself; s; p-450; ourselves; myself; mine; oneself; herself; adrb1; 's; y-27632; wether; thy; theirs; s351; pubchem; poly-(ethylene; poly(amidoamine; p63rhogef; osi-027; myriad; mtorc1
                   proper nouns: SARS; CoV-2; COVID-19; Drug; mg; HIV; C; FDA; RNA; Fig; Health; NMR; CoV; CT; HCV; MRI; B; •; II; Table; US; A; MD; Mpro; T; pH; Hospital; China; kcal; ACE2; Coronavirus; MR; Report; MERS; PLA; University; M; Case; kg; NPs; TB; S; Purpose; remdesivir; vivo; J; CQ; Food; Administration; K
                       keywords: drug; sars; covid-19; patient; cell; delivery; treatment; virus; protein; study; fda; effect; target; hiv; dna; rna; disease; clinical; result; nanoparticle; mpro; cov-2; lung; hcv; cancer; antiviral; ace2; new; model; university; resistance; mers; increase; channel; viral; therapy; structure; respiratory; research; receptor; rat; pulmonary; product; peptide; overdose; mouse; method; il-6; human; host

       one topic; one dimension: drug
                        file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771849/
                      titles(s): Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine

    three topics; one dimension: drug; drug; patients
                        file(s): https://api.elsevier.com/content/article/pii/B9780444505149500073, https://doi.org/10.1016/j.addr.2020.08.008, https://www.ncbi.nlm.nih.gov/pubmed/28074393/
                      titles(s): VII Digestive System 1 | Recent trends in protein and peptide-based biomaterials for advanced drug delivery | 45th ESCP-NSF international symposium on clinical pharmacy: clinical pharmacy tackling inequalities and access to health care. Oslo, Norway, 5–7 October 2016

  five topics; three dimensions: drug cells protein; drug patients health; drug drugs based; delivery drug nanoparticles; patients cells drug
                        file(s): https://api.elsevier.com/content/article/pii/B9780128133743000168, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711696/, https://api.elsevier.com/content/article/pii/B9780128018149000052, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504550/, https://api.elsevier.com/content/article/pii/B9780444505149500073
                      titles(s): Antiviral Evaluation of Herbal Drugs | Section II: Poster Sessions | Chapter 5 Network Pharmacology | Stimulus-Responsive Nanomedicines for Disease Diagnosis and Treatment | VII Digestive System 1

      Type: cord
     title: keyword-drug-cord
      date: 2021-05-24
      time: 23:34
  username: emorgan
    patron: Eric Morgan
     email: emorgan@nd.edu
     input: keywords:drug
==== make-pages.sh htm files
==== make-pages.sh complex files
==== make-pages.sh named enities
==== making bibliographics
         id: cord-256118-gxhhwqdd
     author: Abadie, R.
      title: “Caballo”: risk environments, drug sharing and the emergence of a hepatitis C virus epidemic among people who inject drugs in Puerto Rico
       date: 2020-10-23
      words: 7854.0
  sentences: 337.0
      pages: 
     flesch: 54.0
      cache: ./cache/cord-256118-gxhhwqdd.txt
        txt: ./txt/cord-256118-gxhhwqdd.txt
    summary: Based on a study of PWID in Colorado, Koester (2005) suggests that indirect sharing, which happens when powder drugs are diluted in water before been divided up in a cooker with the help of a syringe, is an efficient way of distributing drugs among injection partners. Nested within a study of social networks and HIV/ HCV risk among PWID in rural Puerto Rico, we propose an ethnographically informed approach to "caballo", the joint acquisition and sharing of drugs, as a window into the social production of an HCV epidemic among PWID. While drug sharing arrangements among PWID have been amply documented, an ethnographic study of caballo in Puerto Rico will illuminate the social context behind the joint acquisition and use of drugs and its related epidemiological risk.
   abstract: BACKGROUND: Sharing drug injection equipment has been associated with the transmission of HCV among PWID through blood contained in the cooker and cotton used to prepare and divide up the drug solution. While epidemiologists often subsume this practice under the sharing of “ancillary equipment,” more attention should be paid to the fact that indirect sharing takes place within the process of joint drug acquisition and preparation. METHODS: We employed an ethnographic approach observing active PWID (N = 33) in four rural towns in Puerto Rico in order to document drug sharing arrangements involved in “caballo”, as this practice is locally known. We explored partners’ motivation to engage in drug sharing, as well as its social organization, social roles and existing norms. FINDINGS: Findings suggest that drug sharing, is one of the main drivers of the HCV epidemic in this population. Lack of financial resources, drug packaging, drug of choice and the desire to avoid the painful effects of heroin withdrawal motivates participants’ decision to partner with somebody else, sharing injection equipment—and risk—in the process. Roles are not fixed, changing not only according to caballo partners, but also, power dynamics. CONCLUSION: In order to curb the HCV epidemic, harm reduction policies should recognize the particular sociocultural contexts in which people inject drugs and make decisions about risk. Avoiding sharing of injection equipment within an arrangement between PWID to acquire and use drugs is more complex than assumed by harm reduction interventions. Moving beyond individual risk behaviors, a risk environment approach suggest that poverty, and a strict drug policy that encourage users to carry small amounts of illicit substances, and a lack of HCV treatment among other factors, contribute to HCV transmission.
        url: https://doi.org/10.1186/s12954-020-00421-z
        doi: 10.1186/s12954-020-00421-z

         id: cord-280819-z6ucnwk0
     author: Achilonu, Ikechukwu
      title: Targeting the SARS-CoV-2 main protease using FDA-approved Isavuconazonium, a P2-P3 α-ketoamide derivative and Pentagastrin: an in-silico drug discovery approach
       date: 2020-09-02
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The SARS-CoV-2 main protease (M(pro)) is an attractive target towards discovery of drugs to treat COVID-19 because of its key role in virus replication. The atomic structure of M(pro) in complex with an α-ketoamide inhibitor (Lig13b) is available (PDB ID:6Y2G). Using 6Y2G and the prior knowledge that protease inhibitors could eradicate COVID-19, we designed a computational study aimed at identifying FDA-approved drugs that could interact with M(pro). We searched the DrugBank and PubChem for analogs and built a virtual library containing ∼33000 conformers. Using high-throughput virtual screening and ligand docking, we identified Isavuconazonium, a ketoamide inhibitor (α-KI) and Pentagastrin as the top three molecules (Lig13b as the benchmark) based on docking energy. The ΔG(bind) of Lig13b, Isavuconazonium, α-KI, Pentagastrin was -28.1, -45.7, -44.7, -34.8 kcal/mol, respectively. Molecular dynamics simulation revealed that these ligands are stable within the M(pro) active site. Binding of these ligands is driven by a variety of non-bonded interaction, including polar bonds, H-bonds, van der Waals and salt bridges. The overall conformational dynamics of the complexed-M(pro) was slightly altered relative to apo-M(pro). This study demonstrates that three distinct classes molecules, Isavuconazonium (triazole), α-KI (ketoamide) and Pentagastrin (peptide) could serve as potential drugs to treat patients with COVID-19.
        url: https://doi.org/10.1016/j.jmgm.2020.107730
        doi: 10.1016/j.jmgm.2020.107730

         id: cord-255460-r5p5helx
     author: Aggarwal, Sadhna
      title: Drug repurposing for breast cancer therapy: Old weapon for new battle
       date: 2019-09-21
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Abstract Despite tremendous resources being invested in prevention and treatment, breast cancer remains a leading cause of cancer deaths in women globally. The available treatment modalities are very costly and produces severe side effects. Drug repurposing that relate to new uses for old drugs has emerged as a novel approach for drug development. Repositioning of old, clinically approved, off patent non-cancer drugs with known targets, into newer indication is like using old weapons for new battle. The advances in genomics, proteomics and information computational biology has facilitated the process of drug repurposing. Repositioning approach not only fastens the process of drug development but also offers more effective, cheaper, safer drugs with lesser/known side effects. During the last decade, drugs such as alkylating agents, anthracyclins, antimetabolite, CDK4/6 inhibitor, aromatase inhibitor, mTOR inhibitor and mitotic inhibitors has been repositioned for breast cancer treatment. The repositioned drugs have been successfully used for the treatment of most aggressive triple negative breast cancer. The literature review suggest that serendipity plays a major role in the drug development. This article describes the comprehensive overview of the current scenario of drug repurposing for the breast cancer treatment. The strategies as well as several examples of repurposed drugs are provided. The challenges associated with drug repurposing are discussed.
        url: https://doi.org/10.1016/j.semcancer.2019.09.012
        doi: 10.1016/j.semcancer.2019.09.012

         id: cord-304617-5ozf18lg
     author: Al-Khafaji, Khattab
      title: Using integrated computational approaches to identify safe and rapid treatment for SARS-CoV-2
       date: 2020-05-15
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: SARS-CoV-2 is a new generation of coronavirus, which was first determined in Wuhan, China, in December 2019. So far, however, there no effective treatment has been found to stop this new generation of coronavirus but discovering of the crystal structure of SARS-CoV-2 main protease (SARS-CoV-2 Mpro) may facilitate searching for new therapies for SARS-COV-2. The aim was to assess the effectiveness of available FDA approved drugs which can construct a covalent bond with Cys145 inside binding site SARS-CoV-2 main protease by using covalent docking screening. We conducted the covdock module MMGBSA module in the Schrodinger suite 2020-1, to examine the covalent bonding utilizing. Besides, we submitted the top three drugs to molecular dynamics simulations via Gromacs 2018.1. The covalent docking showed that saquinavir, ritonavir, remdesivir, delavirdine, cefuroxime axetil, oseltamivir and prevacid have the highest binding energies MMGBSA of –72.17, −72.02, −65.19, −57.65, −54.25, −51.8, and −51.14 kcal/mol, respectively. The 50 ns molecular dynamics simulation was conducted for saquinavir, ritonavir and remdesivir to evaluate the stability of these drugs inside the binding pocket of SARS-CoV-2 main protease. The current study provides a powerful in silico results, means for rapid screening of drugs as anti-protease medications and recommend that the above-mentioned drugs can be used in the treatment of SARS-CoV-2 in combined or sole therapy. Communicated by Ramaswamy H. Sarma
        url: https://doi.org/10.1080/07391102.2020.1764392
        doi: 10.1080/07391102.2020.1764392

         id: cord-263840-1t4ykc01
     author: Altay, Ozlem
      title: Current status of COVID-19 therapies and drug repositioning applications
       date: 2020-06-20
      words: 2099.0
  sentences: 140.0
      pages: 
     flesch: 44.0
      cache: ./cache/cord-263840-1t4ykc01.txt
        txt: ./txt/cord-263840-1t4ykc01.txt
    summary: Summary The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for treatment of COVID-19. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. At the genome 60 level, SARS-CoV-2 has 79·5% homology to SARS CoVCoV-2 and other coronaviruses, and its relative ease of sample acquisition and study, it has been widely 75 accepted that drug repositioning is a promising approach to make available an effective, safety-assured 76 treatment in a timely manner. In this review, we summarize diagnosis approaches, risk groups, available 77 treatment options, and drug repositioning studies related to COVID-19. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 525 2019 (COVID-19): The experience of clinical immunologists from China
   abstract: Summary The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in-silico studies of drug development efforts against SARS-CoV-2.
        url: https://api.elsevier.com/content/article/pii/S2589004220304909
        doi: 10.1016/j.isci.2020.101303

         id: cord-283956-zgrtux7i
     author: Amin, Sk. Abdul
      title: Fight against novel coronavirus: A perspective of medicinal chemists
       date: 2020-06-12
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The ongoing novel coronavirus disease (COVID-19) pandemic makes us painfully perceive that our bullet shells are blank so far for fighting against severe human coronavirus (HCoV). In spite of vast research work, it is crystal clear that the evident does not warrant the commercial blossoming of anti-HCoV drugs. In this circumstance, drug repurposing and/or screening of databases are the only fastest option. This study is an initiative to recapitulate the medicinal chemistry of severe acute respiratory syndrome (SARS)-CoV-2 (SARS-CoV-2). The aim is to present an exquisite delineation of the current research from the perspective of a medicinal chemist to allow the rapid development of anti-SARS-CoV-2 agents.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32563814/
        doi: 10.1016/j.ejmech.2020.112559

         id: cord-321741-aq76s37x
     author: Andersen, Petter I.
      title: Discovery and development of safe-in-man broad-spectrum antiviral agents
       date: 2020-04-30
      words: 5432.0
  sentences: 308.0
      pages: 
     flesch: 41.0
      cache: ./cache/cord-321741-aq76s37x.txt
        txt: ./txt/cord-321741-aq76s37x.txt
    summary: Although the concept of BSAAs has been around for almost 50 years, the field received a new impetus with recent outbreaks of Ebola, Zika, Dengue, influenza and other viral infections, the discovery of novel host-directed agents, as well as development of drug repositioning methodology. The discovery of novel activities of BSAAs starts with exposing cells to the candidate antiviral agent at different concentrations and infecting the cells with a virus or mock. Given that emetine also inhibits ZIKV, EBOV, RABV, CMV, HCoV-OC43 and HIV-1 infections (Chaves Valadao et al., 2015; MacGibeny et al., 2018; Mukhopadhyay et al., 2016; Shen et al., 2019; Yang et al., 2018) , and that it is an FDA-approved anti-protozoal drug, it may represent a promising safe-in-man BSAA candidate. Thereby, novel antiviral activities of BSAAs should be further validated in primary human cells using different viral strains (including wild-type viruses), different viral loads, different times of compound addition, different endpoint measurements and compound concentration range.
   abstract: Abstract Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of the general population from emerging and re-emerging viral diseases, reinforcing the arsenal of available antiviral options. Here, we review discovery and development of BSAAs and summarize the information on 120 safe-in-man agents in a freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand the spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.
        url: https://www.sciencedirect.com/science/article/pii/S120197122030076X
        doi: 10.1016/j.ijid.2020.02.018

         id: cord-318048-6nvi63rq
     author: Arshad, Usman
      title: Prioritisation of Anti‐SARS‐Cov‐2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics
       date: 2020-05-21
      words: 5663.0
  sentences: 288.0
      pages: 
     flesch: 46.0
      cache: ./cache/cord-318048-6nvi63rq.txt
        txt: ./txt/cord-318048-6nvi63rq.txt
    summary: An indication of the degree to which candidate drugs are expected to accumulate in lung (a presumed site of primary efficacy and for prevention of SARS-CoV-2 infection) was provided by calculation of unbound Accepted Article lung to plasma tissue partition coefficient (K p U lung ) according to the methodology of Rodgers and Rowland (20-22). All rights reserved Simulated exposure relative to reported anti-SARS-CoV-2 activity in lung and other tissues Lung K p U was simulated for all molecules for which the necessary physicochemical properties and in vitro drug binding information were available. The rank order of lung Cmax/EC 90 ratio was chloroquine > atazanavir (ritonavir boosted) > tipranavir (ritonavir boosted) > hydroxychloroquine > mefloquine > ivermectin > lopinavir (ritonavir boosted) > azithromycin > nitazoxanide > ritonavir > gilteritinib > amodiaquine > imatinib > oxprenolol (data excluded due to this analysis only being possible for 33 of the 56 drugs).
   abstract: There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against SARS‐CoV‐2. However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, EC(90) values recalculated from in vitro anti‐SARS‐CoV‐2 activity data was expressed as a ratio to the achievable maximum plasma concentrations (Cmax) at an approved dose in humans (Cmax/EC(90) ratio). Only 14 of the 56 analysed drugs achieved a Cmax/EC(90) ratio above 1. A more in‐depth assessment demonstrated that only nitazoxanide, nelfinavir, tipranavir (ritonavir‐boosted) and sulfadoxine achieved plasma concentrations above their reported anti‐SARS‐CoV‐2 activity across their entire approved dosing interval. An unbound lung to plasma tissue partition coefficient (K(p)U(lung)) was also simulated to derive a lung Cmax/EC(50) as a better indicator of potential human efficacy. Hydroxychloroquine, chloroquine, mefloquine, atazanavir (ritonavir‐boosted), tipranavir (ritonavir‐boosted), ivermectin, azithromycin and lopinavir (ritonavir‐boosted) were all predicted to achieve lung concentrations over 10‐fold higher than their reported EC(50). Nitazoxanide and sulfadoxine also exceeded their reported EC(50) by 7.8‐ and 1.5‐fold in lung, respectively. This analysis may be used to select potential candidates for further clinical testing, while deprioritising compounds unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC(90) values and discuss findings in the context of achievable exposures in humans, especially within target compartments such as the lung, in order to maximise the potential for success of proposed human clinical trials.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32438446/
        doi: 10.1002/cpt.1909

         id: cord-314827-yqr7110e
     author: Attia, Yasmeen M.
      title: Successful stories of drug repurposing for cancer therapy in hepatocellular carcinoma
       date: 2020-09-04
      words: 6483.0
  sentences: 300.0
      pages: 
     flesch: 28.0
      cache: ./cache/cord-314827-yqr7110e.txt
        txt: ./txt/cord-314827-yqr7110e.txt
    summary: Since HCC almost exclusively develops in patients with chronic liver diseases, injury of liver cells can promote the progression to HCC over a long period of time [11] driven by a number of cytokines and inflammatory mediators along with aberrant activity of several signaling pathways, as shown in Fig. 8 .1 (will be discussed later). Successful stories of drug repurposing for cancer therapy in hepatocellular carcinoma and HBV-and HCV-related proteins induction are among the mechanisms by which the Ras/ Raf/MAPK pathway can be activated toward HCC development [30] . Successful stories of drug repurposing for cancer therapy in hepatocellular carcinoma (genetically induced liver tumors and patientderived xenografts [PDXs]) for HCC to show significant reduction in the tumor growth after oral administration of NEN compared to niclosamide. Successful stories of drug repurposing for cancer therapy in hepatocellular carcinoma phenotypic events starting with induction of cell cycle arrest at G0/G12 phase accompanied with significant reduction in cell growth with elevated levels of KLF6/p21 protein content in HepG-2 cell line.
   abstract: This chapter offers comprehensive overview for successful stories for drug repurposing/repositioning for affiliated molecular targets related to the progression of hepatocellular carcinoma (HCC). There are detailed sections about the etiology, pathogenesis, current therapeutic regimen, and affiliated molecular targets contributing to HCC. Drug repositioning has been an emerging successful tool for the drug discovery process within the last decade to repurpose new clinical indications for already existing drugs with established safety and pharmacokinetics profiles. In this chapter, we focused on correlating the adopted strategies for drug repositioning targeting molecular targets affiliated with HCC along with different drugs preidentified for other clinical indication.
        url: https://www.sciencedirect.com/science/article/pii/B9780128196687000087
        doi: 10.1016/b978-0-12-819668-7.00008-7

         id: cord-297010-imciixde
     author: Babayeva, Mariana
      title: Repurposing Drugs for COVID-19: Pharmacokinetics and Pharmacogenomics of Chloroquine and Hydroxychloroquine
       date: 2020-10-23
      words: 7080.0
  sentences: 519.0
      pages: 
     flesch: 48.0
      cache: ./cache/cord-297010-imciixde.txt
        txt: ./txt/cord-297010-imciixde.txt
    summary: 81 Similar doses of the two drugs produced 11-fold variations in the blood concentrations in patients with rheumatoid arthritis 47, 63, 82, 83 and in healthy volunteers, 52, 64 suggesting different extend of metabolism among individuals. Determination of CYP3A, CYP2C8 and CYP2D6 polymorphism and, therefore, activity is important to establish safe and efficient dosing of chloroquine and hydroxychloroquine for treatment of COVID-19 patients. 125 Overall, the results suggest that CYP2C8, CYP2D6 and CYP3A genetic polymorphisms may influence chloroquine and hydroxychloroquine pharmacokinetics and COVID-19 patients treated with the same dose of CQ or HCQ may exhibit lack of efficacy or adverse reactions. Despite the evidence of the influence of genetic polymorphisms on the pharmacokinetics of chloroquine and hydroxychloroquine, no large pharmacogenomics studies have been conducted to provide guidance on the use, dosing, and duration of the therapy in COVID-19 patients.
   abstract: BACKGROUND: A new coronavirus SARS-CoV-2 has been identified as the etiological agent of the severe acute respiratory syndrome, COVID-19, the source and cause of the 2019–20 coronavirus pandemic. Hydroxychloroquine and chloroquine have gathered extraordinary attention as therapeutic candidates against SARS-CoV-2 infections. While there is growing scientific data on the therapeutic effect, there is also concern for toxicity of the medications. The therapy of COVID-19 by hydroxychloroquine and chloroquine is off-label. Studies to analyze the personalized effect and safety are lacking. METHODS: A review of the literature was performed using Medline/PubMed/Embase database. A variety of keywords were employed in keyword/title/abstract searches. The electronic search was followed by extensive hand searching using reference lists from the identified articles. RESULTS: A total of 126 results were obtained after screening all sources. Mechanisms underlying variability in drug concentrations and therapeutic response with chloroquine and hydroxychloroquine in mediating beneficial and adverse effects of chloroquine and hydroxychloroquine were reviewed and analyzed. Pharmacogenomic studies from various disease states were evaluated to elucidate the role of genetic variation in drug response and toxicity. CONCLUSION: Knowledge of the pharmacokinetics and pharmacogenomics of chloroquine and hydroxychloroquine is necessary for effective and safe dosing and to avoid treatment failure and severe complications.
        url: https://doi.org/10.2147/pgpm.s275964
        doi: 10.2147/pgpm.s275964

         id: cord-332271-slouuryl
     author: Baker, Jeremy D.
      title: A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV-2 main protease
       date: 2020-08-27
      words: nan
  sentences: nan
      pages: 
     flesch: nan
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    summary: 
   abstract: The SARS coronavirus type 2 (SARS-CoV-2) emerged in late 2019 as a zoonotic virus highly transmissible between humans that has caused the COVID-19 pandemic 1,2. This pandemic has the potential to disrupt healthcare globally and has already caused high levels of mortality, especially amongst the elderly. The overall case fatality rate for COVID-19 is estimated to be ∼2.3% overall 3 and 32.3% in hospitalized patients age 70-79 years 4. Therapeutic options for treating the underlying viremia in COVID-19 are presently limited by a lack of effective SARS-CoV-2 antiviral drugs, although steroidal anti-inflammatory treatment can be helpful. A variety of potential antiviral targets for SARS-CoV-2 have been considered including the spike protein and replicase. Based upon previous successful antiviral drug development for HIV-1 and hepatitis C, the SARS-CoV-2 main protease (Mpro) appears an attractive target for drug development. Here we show the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of ∼6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro. In our primary screen we found ∼50 compounds with activity against Mpro (overall hit rate <0.75%). Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 ≤ 50 μM. Hits from our screen are enriched with hepatitis C NS3/4A protease targeting drugs including Boceprevir (IC50=0.95 μM), Ciluprevir (20.77μM). Narlaprevir (IC50=1.10μM), and Telaprevir (15.25μM). These results demonstrate that some existing approved drugs can inhibit SARS-CoV-2 Mpro and that screen saturation of all approved drugs is both feasible and warranted. Taken together this work suggests previous large-scale commercial drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some previous lead compounds may be more potent against SARS-CoV-2 Mpro than Boceprevir and suitable for rapid repurposing.
        url: https://doi.org/10.1101/2020.07.10.197889
        doi: 10.1101/2020.07.10.197889

         id: cord-345059-t6hojshj
     author: Bayoumy, A. B.
      title: Unrealized potential of drug repositioning in europe during COVID-19 and beyond: a physcian’s perspective
       date: 2020-07-17
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Drug repositioning is the scientific strategy of investigating existing drugs for additional clinical indications. The advantages of drug repositioning are that it benefits patients and that it adds new indications to existing drugs for lower costs compared to de novo drug development. Clinical research groups recognizing efficacy of these “old” drugs for a new indications often face an uphill struggle due to a lack of funding and support because of poor structural and regulatory support for clinical drug development. The current framework for drug repositioning allows “venture capital” companies to abuse loopholes in the legislation to gain long-term market authorization among with excessive high pricing. A new regulatory framework is needed to prevent abuse of the legislation and promote clinical investigator-driven drug repositioning. The COVID-19 pandemic has boosted funding and regulatory support for drug repositioning. The lessons learned from the COVID-19 pandemic should be implemented in a new clear blueprint for drug repositioning. This blueprint should guide clinicians through legislation for drug repositioning in the EU. This review summarizes the routes for registration and discusses the current state of drug repositioning in Europe.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32695427/
        doi: 10.1186/s40545-020-00249-9

         id: cord-311730-189vax2m
     author: Becker, Richard C.
      title: Covid-19 treatment update: follow the scientific evidence
       date: 2020-04-27
      words: 4514.0
  sentences: 222.0
      pages: 
     flesch: 40.0
      cache: ./cache/cord-311730-189vax2m.txt
        txt: ./txt/cord-311730-189vax2m.txt
    summary: The SNS exists under the authority of the United States Department of Health and Human Services (HHS) and accepted 30 million doses of hydroxychloroquine sulfate donated by Sandoz™, the Novartis™ generics and biosimilars division, and one million doses of chloroquine phosphate donated by Bayer Pharmaceuticals™ for potential use in treating patients who were hospitalized with COVID-19 or for use in clinical trials. The adverse effects associated with taking hydroxychloroquine are similar to those observed with chloroquine and include nausea, vomiting, diarrhea, AV conduction defects, a prolonged QTc interval with torsades de pointe ventricular tachycardia, hypokalemia, hypotension and circulatory collapse. Similarly, patients with Covid-19 for whom a clinician believes that either chloroquine or hydroxychloroquine is indicated must receive information, preferably in the form of a fact sheet that clearly summarized the dose, duration of treatment, potential risks, side-effects and drug-drug interactions.
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pubmed/32338320/
        doi: 10.1007/s11239-020-02120-9

         id: cord-016460-39yniw0t
     author: Ben-Chetrit, Eldad
      title: Colchicine
       date: 2018-07-31
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Colchicine is an alkaloid which was originally extracted from bulbs of a plant called Colchicum autumnale (meadow saffron). Its active pharmacological component was isolated in 1820 and in 1833 the active ingredient was purified and named colchicine. It consists of three hexameric rings termed A, B, and C. It was first recommended for the treatment of gout by Alexander of Tralles in the sixth century AD. Later it has been employed for suggested and approved indications including primary biliary cirrhosis (PBC), alcohol induced hepatitis, psoriasis, Behçet disease, Sweet syndrome, scleroderma, sarcoidosis and amyloidosis. Perhaps the most effective results have been obtained in the prophylaxis of familial Mediterranean fever (FMF). Colchicine is absorbed in the jejunum and ileum and is trapped in the body tissues. It is metabolized in the liver and the intestine by cytochrome P (CYP) 450 3A4 and P-glycoprotein (PGY) 1. Colchicine is excreted mainly by the biliary system, intestines and the kidneys. It has a narrow therapeutic range, but with normal liver and kidney functions is relatively safe and can be used during pregnancy, nursing and in infants. The main mechanism of action of colchicine is probably through interaction with microtubules affecting leukocyte chemotaxis, thereby suppressing inflammation. The blood level of colchicine may be affected by concomitant drug administration and therefore, caution should be exercised when such medications are added.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120738/
        doi: 10.1007/978-3-319-98605-0_40

         id: cord-325019-hznnoxw6
     author: Benavides-Cordoba, Vicente
      title: Drug Repositioning for COVID-19
       date: 2020-06-30
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Drug repositioning is a strategy that identifies new uses of approved drugs to treat conditions different from their original purpose. With the advance of COVID-19 and the pandemic declaration; It has become the closest alternative to reduce the advance of the virus. Antimalarial, antiviral drugs, antibiotics, glucocorticoids, monoclonal antibodies, among others, are being studied; their findings, although preliminary, could establish a starting point in the search for a solution. In this review, we present a selection of drugs, of different classes and with potential activity against COVID-19, whose trials are ongoing; and as proofs of concept, double blind, add-on event-driven, would allow proposing research that generates results in less time and preserving quality criteria for drug development and approval by regulatory agencies.
        url: https://doi.org/10.25100/cm.v51i2.4279
        doi: 10.25100/cm.v51i2.4279

         id: cord-333122-xw8o189s
     author: Blasiak, A.
      title: IDentif.AI: Artificial Intelligence Pinpoints Remdesivir in Combination with Ritonavir and Lopinavir as an Optimal Regimen Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
       date: 2020-05-08
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) has led to the rapid initiation of urgently needed clinical trials of repurposed drug combinations and monotherapies. These regimens were primarily relying on mechanism-of-action based selection of drugs, many of which have yielded positive in vitro but largely negative clinical outcomes. To overcome this challenge, we report the use of IDentif.AI, a platform that rapidly optimizes infectious disease (ID) combination therapy design using artificial intelligence (AI). In this study, IDentif.AI was implemented on a 12-drug candidate therapy search set representing over 530,000 possible drug combinations. IDentif.AI demonstrated that the optimal combination therapy against SARS-CoV-2 was comprised of remdesivir, ritonavir, and lopinavir, which mediated a 6.5-fold improvement in efficacy over remdesivir alone. Additionally, IDentif.AI showed hydroxychloroquine and azithromycin to be relatively ineffective. The identification of a clinically actionable optimal drug combination was completed within two weeks, with a 3-order of magnitude reduction in the number of tests typically needed. IDentif.AI analysis was also able to independently confirm clinical trial outcomes to date without requiring any data from these trials. The robustness of the IDentif.AI platform suggests that it may be applicable towards rapid development of optimal drug regimens to address current and future outbreaks.
        url: https://doi.org/10.1101/2020.05.04.20088104
        doi: 10.1101/2020.05.04.20088104

         id: cord-303089-fbxtj8ij
     author: Boccaletti, Valeria
      title: Acute generalized exanthematous pustulosis following paracetamol ingestion in a child
       date: 2015-05-24
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pubmed/25845401/
        doi: 10.1111/pai.12386

         id: cord-274307-kl0uvrbw
     author: Bordet, Régis
      title: Is the drug a scientific, social or political object?
       date: 2020-05-23
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: nan
        url: https://api.elsevier.com/content/article/pii/S0040595720301025
        doi: 10.1016/j.therap.2020.05.012

         id: cord-316029-z708c3ex
     author: Brunsdon, Priya
      title: Clinical Pharmacology Considerations for Developing Small‐Molecule Treatments for COVID‐19
       date: 2020-07-12
      words: 4964.0
  sentences: 264.0
      pages: 
     flesch: 36.0
      cache: ./cache/cord-316029-z708c3ex.txt
        txt: ./txt/cord-316029-z708c3ex.txt
    summary: This review will offer key clinical pharmacology considerations for developing small molecules for the treatment of COVID-19 based on the major disease complications that impact drug absorption, distribution, metabolism, and elimination (ADME). Of major concern is sepsis, defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection." 12 In 1 study, septic shock, which is distinguished by persistent hypotension, elevated serum lactate levels, and increased mortality, was a complication in about 6% of severely ill COVID-19 patients. For water-soluble investigational therapies that are intended for administration in the severely ill COVID-19 population, thought should be given to targeting serum drug concentrations and the drug''s exposure-response profile when determining if increased doses would be beneficial for patients receiving intravenous fluids. 21 The clinical impact of these potential changes in free drug fractions on investigational therapies that are highly proteinbound is an important consideration when empirically selecting doses for critically ill COVID-19 patients.
   abstract: Numerous drugs are being investigated for the treatment of COVID‐19, including antivirals and therapies targeting complications related to COVID‐19. The clinical presentation of COVID‐19 varies from mild fever, cough, and dyspnea in the early stages of disease to severe complications such as acute respiratory distress syndrome, systemic hyperinflammation, and sepsis. A thorough understanding of the disease pathogenesis and the disease complications is essential to developing effective therapies to treat this potentially life‐threatening disease. This review offers key clinical pharmacology considerations involved in the development of small molecules for the treatment of COVID‐19. They are based on the major observed disease complications that impact drug absorption, distribution, metabolism, and elimination. We also address considerations regarding potential drug interactions, alternative routes and methods of administration, and dosing in patients on hemodialysis.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32579707/
        doi: 10.1002/jcph.1697

         id: cord-351185-3y3gou6v
     author: Buckles, Thomas C.
      title: Rapid exposure of macrophages to drugs resolves four classes of effects on the leading edge sensory pseudopod: Non-perturbing, adaptive, disruptive, and activating
       date: 2020-05-29
      words: 10061.0
  sentences: 465.0
      pages: 
     flesch: 45.0
      cache: ./cache/cord-351185-3y3gou6v.txt
        txt: ./txt/cord-351185-3y3gou6v.txt
    summary: However, rapid drug addition to cultured macrophages revealed four distinct classes of effects on the leading edge pseudopod: (i) non-perturbing drug exposures yielded no detectable change in pseudopod morphology (acetylsalicylic acid, diclofenac); (ii) adaptive exposures yielded temporary collapse of the extended pseudopod and its signature PI(3,4,5)P(3) lipid signal followed by slow recovery of extended pseudopod morphology (ibuprofen, acetaminophen); (iii) disruptive exposures yielded long-term pseudopod collapse (Gö6976, wortmannin); and (iv) activating exposures yielded pseudopod expansion (PDGF). In contrast, ibuprofen and acetaminophen are classified as adaptive because rapid addition of either drug to polarized cells yields short-term collapse of the leading edge pseudopod and loss of the PIP 3 signal, followed by slow recovery. In contrast to the four therapeutic adaptive drugs, the two non-clinical control inhibitors wortmannin and Gö6976 are each known to directly inhibit key components of the leading edge positive feedback loop and rapid addition is observed herein to trigger long term collapse of the pseudopod with no detected recovery as previously observed [26, 30, [50] [51] [52] [53] [54] .
   abstract: Leukocyte migration is controlled by a membrane-based chemosensory pathway on the leading edge pseudopod that guides cell movement up attractant gradients during the innate immune and inflammatory responses. This study employed single cell and population imaging to investigate drug-induced perturbations of leading edge pseudopod morphology in cultured, polarized RAW macrophages. The drugs tested included representative therapeutics (acetylsalicylic acid, diclofenac, ibuprofen, acetaminophen) as well as control drugs (PDGF, Gö6976, wortmannin). Notably, slow addition of any of the four therapeutics to cultured macrophages, mimicking the slowly increasing plasma concentration reported for standard oral dosage in patients, yielded no detectable change in pseudopod morphology. This finding is consistent with the well established clinical safety of these drugs. However, rapid drug addition to cultured macrophages revealed four distinct classes of effects on the leading edge pseudopod: (i) non-perturbing drug exposures yielded no detectable change in pseudopod morphology (acetylsalicylic acid, diclofenac); (ii) adaptive exposures yielded temporary collapse of the extended pseudopod and its signature PI(3,4,5)P(3) lipid signal followed by slow recovery of extended pseudopod morphology (ibuprofen, acetaminophen); (iii) disruptive exposures yielded long-term pseudopod collapse (Gö6976, wortmannin); and (iv) activating exposures yielded pseudopod expansion (PDGF). The novel observation of adaptive exposures leads us to hypothesize that rapid addition of an adaptive drug overwhelms an intrinsic or extrinsic adaptation system yielding temporary collapse followed by adaptive recovery, while slow addition enables gradual adaptation to counteract the drug perturbation in real time. Overall, the results illustrate an approach that may help identify therapeutic drugs that temporarily inhibit the leading edge pseudopod during extreme inflammation events, and toxic drugs that yield long term inhibition of the pseudopod with negative consequences for innate immunity. Future studies are needed to elucidate the mechanisms of drug-induced pseudopod collapse, as well as the mechanisms of adaptation and recovery following some inhibitory drug exposures.
        url: https://doi.org/10.1371/journal.pone.0233012
        doi: 10.1371/journal.pone.0233012

         id: cord-016309-6mw8okmt
     author: Bule, Mohammed
      title: Antivirals: Past, Present and Future
       date: 2019-06-06
      words: 8200.0
  sentences: 405.0
      pages: 
     flesch: 36.0
      cache: ./cache/cord-016309-6mw8okmt.txt
        txt: ./txt/cord-016309-6mw8okmt.txt
    summary: Those included usage restricted to a single virus and specific animal species, problems with high spectrum activity and low cytotoxicity, high costs of development of new chemical compounds and absence of rapid diagnostic techniques allowing prompt use of a specific antiviral agent in the course of an acute infection (Rollinson 1992a, b) . Nevertheless, several licensed human antiviral agents are being used with cascade principle for treatment of animal diseases (e.g. acyclovir, idoxuridine and trifluridine against feline herpesvirus-1 ocular infection in cats) (Thiry et al. The discovery of PAA (Fig. 22.4) as an antiviral drug gave rise to intense research on its biological activities, which demonstrated PAA and its derivatives'' ability to inhibit the replication of a number of viruses such as immunodeficiency, hepatitis and herpes viruses. To conclude with, equine herpesvirus type 1 (EHV-1) infection causes outbreak of respiratory and various neurological diseases in horses, against which acyclovir and valacyclovir are the most common drugs, but also IFN targeting IFNGR complex as a key mediator of virus-specific cellular immunity (Poelaert et al.
   abstract: The uses of antiviral agents are increasing in the new era along with the development of vaccines for the effective control of viral diseases. The main aims of antiviral agents are to minimize harm to the host system and eradicate deadly viral diseases. However, the replications of viruses in host system represent a massive therapeutic challenge than bacteria and fungi. Antiviral drugs not just penetrate to disrupt the virus’ cellular divisions but also have a negative impact on normal physiological pathways in the host. Due to these issues, antiviral agents have a narrow therapeutic index than antibacterial drugs. Nephrotoxicity is the main adverse reaction of antiviral drugs in human and animals. In this chapter, we summarize the antiviral agents’ past, present and future perspectives with the main focus on the brief history of antiviral in animals, miscellaneous drugs, natural products, herbal and repurposing drugs.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120554/
        doi: 10.1007/978-981-13-9073-9_22

         id: cord-342588-berrojmq
     author: Burri, Christian
      title: Sleeping Sickness at the Crossroads
       date: 2020-04-08
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Human African trypanosomiasis (HAT; sleeping sickness) is a disease with truly historic dimensions [...].
        url: https://www.ncbi.nlm.nih.gov/pubmed/32276514/
        doi: 10.3390/tropicalmed5020057

         id: cord-273656-xo82zyi6
     author: Burry, Lisa D.
      title: It Takes a Village… Contending with Drug Shortages During Disasters
       date: 2020-08-14
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: nan
        url: https://doi.org/10.1016/j.chest.2020.08.015
        doi: 10.1016/j.chest.2020.08.015

         id: cord-015684-q10sx1dm
     author: Cacabelos, Ramón
      title: Pharmacogenomic Biomarkers in Neuropsychiatry: The Path to Personalized Medicine in Mental Disorders
       date: 2009
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Neuropsychiatric disorders and dementia represent a major cause of disability and high cost in developed societies. Most disorders of the central nervous system (CNS) share some common features, such as a genomic background in which hundreds of genes might be involved, genome-environment interactions, complex pathogenic pathways, poor therapeutic outcomes, and chronic disability. Recent advances in genomic medicine can contribute to accelerate our understanding on the pathogenesis of CNS disorders, improve diagnostic accuracy with the introduction of novel biomarkers, and personalize therapeutics with the incorporation of pharmacogenetic and pharmacogenomic procedures to drug development and clinical practice. The pharmacological treatment of CNS disorders, in general, accounts for 10–20% of direct costs, and less than 30–40% of the patients are moderate responders to conventional drugs, some of which may cause important adverse drugs reactions (ADRs). Pharmacogenetic and pharmacogenomic factors may account for 60–90% of drug variability in drug disposition and pharmacodynamics. Approximately 60–80% of CNS drugs are metabolized via enzymes of the CYP gene superfamily; 18% of neuroleptics are major substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4; 24% of antidepressants are major substrates of CYP1A2 enzymes, 5% of CYP2B6, 38% of CYP2C19, 85% of CYP2D6, and 38% of CYP3A4; 7% of benzodiazepines are major substrates of CYP2C19 enzymes, 20% of CYP2D6, and 95% of CYP3A4. About 10–20% of Caucasians are carriers of defective CYP2D6 polymorphic variants that alter the metabolism of many psychotropic agents. Other 100 genes participate in the efficacy and safety of psychotropic drugs. The incorporation of pharmacogenetic/ pharmacogenomic protocols to CNS research and clinical practice can foster therapeutics optimization by helping to develop cost-effective pharmaceuticals and improving drug efficacy and safety. To achieve this goal several measures have to be taken, including: (a) educate physicians and the public on the use of genetic/ genomic screening in the daily clinical practice; (b) standardize genetic testing for major categories of drugs; (c) validate pharmacogenetic and pharmacogenomic procedures according to drug category and pathology; (d) regulate ethical, social, and economic issues; and (e) incorporate pharmacogenetic and pharmacogenomic procedures to both drugs in development and drugs in the market to optimize therapeutics.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115027/
        doi: 10.1007/978-90-481-2298-1_1

         id: cord-323940-ubazgvov
     author: Cafiero, Concetta
      title: Pharmacogenomics and Pharmacogenetics: In Silico Prediction of Drug Effects in Treatments for Novel Coronavirus SARS-CoV2 Disease
       date: 2020-10-13
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The latest developments in precision medicine allow the modulation of therapeutic approaches in different pathologies on the basis of the specific molecular characterization of the patient. This review of the literature coupled with in silico analysis was to provide a selected screening of interactions between single-nucleotide polymorphisms (SNPs) and drugs (repurposed, investigational, and biological agents) showing efficacy and toxicityin counteracting Covid-19 infection. In silico analysis of genetic variants related to each drug was performed on such databases as PharmGKB, Ensembl Genome Browser, www.drugs.com, and SNPedia, with an extensive literature review of papers (to May 10, 2020) on Covid-19 treatments using Medline, Embase, International Pharmaceutical Abstracts, PharmGKB, and Google Scholar. The clinical relevance of SNPs, known as both drug targets and markers, considering genetic variations with known drug responses, and the therapeutic consequences are discussed. In the context of clinical treatment of Covid-19, including infection prevention, control measures, and supportive care, this review highlights the importance of a personalized approach in the final selection of therapy, which is probably essential in the management of the Covid-19 pandemic.
        url: https://doi.org/10.2147/pgpm.s270069
        doi: 10.2147/pgpm.s270069

         id: cord-203232-1nnqx1g9
     author: Canturk, Semih
      title: Machine-Learning Driven Drug Repurposing for COVID-19
       date: 2020-06-25
      words: 5023.0
  sentences: 257.0
      pages: 
     flesch: 52.0
      cache: ./cache/cord-203232-1nnqx1g9.txt
        txt: ./txt/cord-203232-1nnqx1g9.txt
    summary: Using the National Center for Biotechnology Information virus protein database and the DrugVirus database, which provides a comprehensive report of broad-spectrum antiviral agents (BSAAs) and viruses they inhibit, we trained ANN models with virus protein sequences as inputs and antiviral agents deemed safe-in-humans as outputs. Using sequences for SARS-CoV-2 (the coronavirus that causes COVID-19) as inputs to the trained models produces outputs of tentative safe-in-human antiviral candidates for treating COVID-19. For Experiment II, we split the data on virus species, meaning the models were forced to predict drugs for a species that it was not trained on, and have to detect peptide substructures in the amino-acid sequences to suggest drugs. In post-processing, we applied a threshold to the sigmoid function outputs of the neural network, where we assigned each drug a probability of being a potential antiviral for a given amino acid sequence.
   abstract: The integration of machine learning methods into bioinformatics provides particular benefits in identifying how therapeutics effective in one context might have utility in an unknown clinical context or against a novel pathology. We aim to discover the underlying associations between viral proteins and antiviral therapeutics that are effective against them by employing neural network models. Using the National Center for Biotechnology Information virus protein database and the DrugVirus database, which provides a comprehensive report of broad-spectrum antiviral agents (BSAAs) and viruses they inhibit, we trained ANN models with virus protein sequences as inputs and antiviral agents deemed safe-in-humans as outputs. Model training excluded SARS-CoV-2 proteins and included only Phases II, III, IV and Approved level drugs. Using sequences for SARS-CoV-2 (the coronavirus that causes COVID-19) as inputs to the trained models produces outputs of tentative safe-in-human antiviral candidates for treating COVID-19. Our results suggest multiple drug candidates, some of which complement recent findings from noteworthy clinical studies. Our in-silico approach to drug repurposing has promise in identifying new drug candidates and treatments for other viruses.
        url: https://arxiv.org/pdf/2006.14707v1.pdf
        doi: nan

         id: cord-302018-3rlya16w
     author: Castells, Mariana C.
      title: Drug allergy labeling and delabeling in the coronavirus disease 2019 era: What is important and what do we need to know
       date: 2020-05-22
      words: 1939.0
  sentences: 97.0
      pages: 
     flesch: 38.0
      cache: ./cache/cord-302018-3rlya16w.txt
        txt: ./txt/cord-302018-3rlya16w.txt
    summary: The topics covered in this issue provide the necessary and updated knowledge for all allergists involved in labeling and delabeling procedures, aiming to broaden drug choices and treatment options for patients in this unknown world of COVID-19 pandemic and other disease states. Target populations for receiving a drug allergy label include the following: (1) children with approximately 70,000 visits to the emergency department reported annually for adverse drug events with penicillins, cephalosporins, and sulfamethoxazole-trimethoprim as the most frequent medications; and (2) hospitalized patients with cancer, of whom 23% have a label of antibiotic allergy. The authors concluded that current and future efforts should focus on preventing penicillin allergy labels that can carry over into adulthood, providing education and decision support in the electronic medical record, and testing low-risk drug administration strategies in low-risk patients. As more mechanisms of drug allergy are uncovered and new biomarkers become available, they can be incorporated into this flexible classification, guiding clinicians toward an optimal approach for patient labeling or delabeling, treatment, and management.
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pubmed/32448437/
        doi: 10.1016/j.anai.2020.04.012

         id: cord-285121-3cjr1rol
     author: Chan, Marion M.
      title: Targeting cancer stem cells with dietary phytochemical - Repositioned drug combinations
       date: 2018-10-01
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The tumor microenvironment is complex with the cancer stem cell (CSC) as a member within its community. This population possesses the capacity to self-renew and to cause cellular heterogeneity of the tumor. CSCs are resistant to conventional anti-proliferative drugs. In order to be curative, it is imperative that CSCs must be eliminated by cancer therapy. A variety of dietary phytochemicals and repositioned drugs can act synergistically with conventional anti-cancer agents. In this review, we advocate the development of a novel approach, namely combination therapy by incorporating both phytochemicals and repositioned drugs to target CSCs. We cover select dietary phytochemicals (curcumin, resveratrol, EGCG, genistein) and repurposed drugs (metformin, niclosamide, thioridazine, chloroquine). Five of the eight (curcumin, resveratrol, EGCG, genistein, metformin) are listed in “The Halifax Project”, that explores “the concept of a low-toxicity ‘broad-spectrum’ therapeutic approach that could simultaneously target many key pathways and mechanisms” [1]. For these compounds, we discuss their mechanisms of action, in which models their anti-CSC activities were identified, as well as advantages, challenges and potentials of combination therapy.
        url: https://www.ncbi.nlm.nih.gov/pubmed/29960048/
        doi: 10.1016/j.canlet.2018.06.034

         id: cord-273941-gu6nnv9d
     author: Chandran, Uma
      title: Chapter 5 Network Pharmacology
       date: 2017-12-31
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Abstract The one-drug/one-target/one-disease approach to drug discovery is presently facing many challenges of safety, efficacy, and sustainability. Network biology and polypharmacology approaches gained appreciation recently as methods for omics data integration and multitarget drug development, respectively. The combination of these two approaches created a novel paradigm called network pharmacology (NP) that looks at the effect of drugs on both the interactome and the diseasome level. Ayurveda, the traditional system of Indian medicine, uses intelligent formulations containing multiple ingredients and multiple bioactive compounds; however, the scientific rationale and mechanisms remain largely unexplored. NP approaches can serve as a valuable tool for evidence-based Ayurveda to understand the medicines’ putative actions, indications, and mechanisms. This chapter discusses NP and its potential to explore traditional medicine systems to overcome the drug discovery impasse.
        url: https://api.elsevier.com/content/article/pii/B9780128018149000052
        doi: 10.1016/b978-0-12-801814-9.00005-2

         id: cord-267608-0odu8lus
     author: Chen, Daohong
      title: Innovative highlights of clinical drug trial design
       date: 2020-06-03
      words: 4164.0
  sentences: 155.0
      pages: 
     flesch: 28.0
      cache: ./cache/cord-267608-0odu8lus.txt
        txt: ./txt/cord-267608-0odu8lus.txt
    summary: Accordingly taking the advantage of interim analysis based on novel biomarker approach for detecting the pathogenesis-specific molecular alteration(s), an adaptive clinical study can select the drug-sensitive sub-population from patients with initially targeted disease or an alternative indication, to continue the investigation for an optimized therapeutic efficacy [7] . While human bioequivalence study is increasingly contributing to evaluation of emerging formulation and bio-similar agents besides chemical generics [4] , several adaptive trial designs have been capable of translating the scientific breakthroughs into novel therapeutic benefits with shorter processing time and lower financial costs, to address the unmet clinical needs [3, 19] . Of note, to preserve the strength of clear defining efficacy and safety of tested drugs, the innovative designs of clinical study are substantially overlapped with classic trial protocols of three phases which still serve as the mainstream approach of clinical investigation [3, 7] .
   abstract: Clinical trials serve as the gold standard to evaluate the efficacy and safety of tested drugs prior to marketing authorization. Nevertheless, there have been a few challenging issues well noted in traditional clinical trials such as tedious processing duration and escalating high costs among others. To improve the efficiency of clinical studies, a spectrum of expedited clinical trial modes has been designed, and selectively implemented in contemporary drug developing landscape. Herein this article presents an update on the innovated human trial designs that are corroborated through coming up with approval of notable therapeutic compounds for clinical utilization including delivery of several blockbuster products. It is intended to inspire clinical investigators and pharmaceutical development not only timely communicating with the regulatory agencies, but also insightful translating from cutting-edge scientific discoveries.
        url: https://doi.org/10.1016/j.trsl.2020.05.007
        doi: 10.1016/j.trsl.2020.05.007

         id: cord-004501-guiy89x8
     author: Cojocaru, Florina-Daniela
      title: Nanomaterials Designed for Antiviral Drug Delivery Transport across Biological Barriers
       date: 2020-02-18
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Viral infections are a major global health problem, representing a significant cause of mortality with an unfavorable continuously amplified socio-economic impact. The increased drug resistance and constant viral replication have been the trigger for important studies regarding the use of nanotechnology in antiviral therapies. Nanomaterials offer unique physico-chemical properties that have linked benefits for drug delivery as ideal tools for viral treatment. Currently, different types of nanomaterials namely nanoparticles, liposomes, nanospheres, nanogels, nanosuspensions and nanoemulsions were studied either in vitro or in vivo for drug delivery of antiviral agents with prospects to be translated in clinical practice. This review highlights the drug delivery nanosystems incorporating the major antiviral classes and their transport across specific barriers at cellular and intracellular level. Important reflections on nanomedicines currently approved or undergoing investigations for the treatment of viral infections are also discussed. Finally, the authors present an overview on the requirements for the design of antiviral nanotherapeutics.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076512/
        doi: 10.3390/pharmaceutics12020171

         id: cord-023509-tvqpv6fp
     author: Corrin, Bryan
      title: Occupational, environmental and iatrogenic lung disease
       date: 2011-03-02
      words: 42576.0
  sentences: 2457.0
      pages: 
     flesch: 45.0
      cache: ./cache/cord-023509-tvqpv6fp.txt
        txt: ./txt/cord-023509-tvqpv6fp.txt
    summary: As a general rule, exposure to silica dust extends over many years, often 20 or more, before the symptoms of silicosis first appear: by the time the disease becomes overt clinically, much irreparable damage has been inflicted on the lungs. Confusingly, the term ''acute silicosis'' has since been applied to a further effect of heavy dust exposure in tunnellers, sand blasters and silica flour workers, namely pulmonary alveolar lipoproteinosis (see below), 71, 72 whilst the terms ''accelerated silicosis'' or ''cellular phase silicosis'' have been substituted for ''acute silicosis'' in referring to the rapid development of early cellular lesions. Asbestosis is defined as diffuse interstitial fibrosis of the lung caused by exposure to asbestos dust. The finely divided fume of several metals is highly toxic to the lungs and capable of producing severe acute and chronic damage to both the conductive airways and the alveoli, resulting in acute tracheobronchitis and bronchiolitis, diffuse alveolar damage, obliterative bronchiolitis and pulmonary fibrosis.
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170212/
        doi: 10.1016/b978-0-7020-3369-8.00007-0

         id: cord-018714-i291z2ju
     author: Criado, Paulo Ricardo
      title: Adverse Drug Reactions
       date: 2016-12-31
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Adverse events and adverse drug reactions are common in clinical practice. Side effects range from the common to the rare and may be confused with other mucocutaneous manifestations resulting from several medications to treat infections, other medical conditions, and in the clinical setting of oncologic treatment. The objective of this chapter to review current data on adverse drug reactions, here classified as (i) severe adverse drug reactions, (ii) uncomplicated cutaneous adverse drug reactions, and (iii) adverse drug reactions caused by chemotherapy drugs, particularly those cases whereby the dermatologist is requested to issue a report and asked to comment on the safety and viability of readministration of a specific drug. We describe aspects associated with these events, presenting a detailed analysis of each of them.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123670/
        doi: 10.1007/978-3-319-33919-1_26

         id: cord-347579-aqgauumt
     author: Csete, Joanne
      title: United States drug courts and opioid agonist therapy: Missing the target of overdose reduction
       date: 2020-06-09
      words: 4141.0
  sentences: 173.0
      pages: 
     flesch: 55.0
      cache: ./cache/cord-347579-aqgauumt.txt
        txt: ./txt/cord-347579-aqgauumt.txt
    summary: • Drug courts overall have had limited success in improving access to OUD treatment and other health and social services needed to achieve significant reduction in overdose death. • Drug courts overall have had limited success in improving access to OUD treatment and other health and social services needed to achieve significant reduction in overdose death. In the face of such a crisis, it might be supposed that policy-makers would do everything possible to reduce overdose risk, including improving access to the several authorized forms of proven treatment for opioid use disorder (OUD). A 2013 national survey of drug courts found that although virtually all of the courts reported having participants with opioid use disorders, only 47% offered agonist therapy as an option for court-supervised treatment (Matusow, Dickman, Rich, Fong, Dumont, Hardin et al., 2013) .
   abstract: • The United States (US) has witnessed dramatic increases in opioid-overdose mortality since 1999. The need for ready access to scientifically sound treatment for opioid use disorder (OUD) is urgent, but gold-standard agonist therapy is often inaccessible. • Drug courts should help to reduce barriers to OUD therapy by offering court-supervised treatment as an alternative to criminal prosecution for certain categories of drug offenses. • Many drug courts, however, reject including the opioid agonist methadone and partial agonist buprenorphine as treatment options, often because these medicines are seen as “another form of addiction”. • Many US drug courts have steered participants to extended-release naltrexone (XR-NTX), an opioid antagonist, sometimes offering only XR-NTX and no agonist therapies. XR-NTX is very expensive in the US market and also requires a period of abstinence before it can be initiated. • Drug courts overall have had limited success in improving access to OUD treatment and other health and social services needed to achieve significant reduction in overdose death.
        url: https://api.elsevier.com/content/article/pii/S2666353820300175
        doi: 10.1016/j.fsiml.2020.100024

         id: cord-343620-64i1balq
     author: Darvishi, Behrad
      title: Preparation and Antibacterial Activity Evaluation of 18-β-glycyrrhetinic Acid Loaded PLGA Nanoparticles
       date: 2015
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The aim of the present study was to formulate poly (lactide-co-glycolide) (PLGA) nanoparticles loaded with 18-β-glycyrrhetinic acid (GLA) with appropriate physicochemical properties and antimicrobial activity. GLA loaded PLGA nanoparticles were prepared with different drug to polymer ratios, acetone contents and sonication times and the antibacterial activity of the developed nanoparticles was examined against different gram-negative and gram-positive bacteria. The antibacterial effect was studied using serial dilution technique to determine the minimum inhibitory concentration of nanoparticles. Results demonstrated that physicochemical properties of nanoparticles were affected by the above mentioned parameters where nanoscale size particles ranging from 175 to 212 nm were achieved. The highest encapsulation efficiency (53.2 ± 2.4%) was obtained when the ratio of drug to polymer was 1:4. Zeta potential of the developed nanoparticles was fairly negative (-11±1.5). In-vitro release profile of nanoparticles showed two phases: an initial phase of burst release for 10 h followed by a slow release pattern up to the end. The antimicrobial results revealed that the nanoparticles were more effective than pure GLA against P. aeuroginosa, S. aureus and S. epidermidis. This improvement in antibacterial activity of GLA loaded nanoparticles when compared to pure GLA may be related to higher nanoparticles penetration into infected cells and a higher amount of GLA delivery in its site of action. Herein, it was shown that GLA loaded PLGA nanoparticles displayed appropriate physicochemical properties as well as an improved antimicrobial effect.
        url: https://www.ncbi.nlm.nih.gov/pubmed/25901144/
        doi: nan

         id: cord-301026-spgidqh3
     author: Das, Shaoli
      title: In silico Drug Repurposing to combat COVID-19 based on Pharmacogenomics of Patient Transcriptomic Data
       date: 2020-06-30
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The ongoing global pandemic of coronavirus disease 2019 (COVID-19) continues to affect a growing number of populations in different parts of the world. In the current situation, drug repurposing is a viable strategy to combat COVID-19. The drugs targeting the host receptors that interact with SARS-CoV-2 are possible candidates. However, assessment of their effectiveness in COVID-19 patients is necessary before prioritizing them for further study. We attempted to shortlist the candidate drugs using an in-silico approach. First, we analysed two published transcriptomic data sets of COVID-19- and SARS-infected patients compared to healthy individuals to find the key pathways altered after infection. Then, using publicly available drug perturbational data sets in human cell lines from the Broad Institute Connectivity Map (CMAP), we assessed the effects of the approved drugs on the altered pathways. We also used the available pharmacogenomic data sets from the Genomics of Drug Sensitivity in Cancer (GDSC) portal to assess the effects of the altered pathways on resistance or sensitivity to the drugs in human cell lines. Our analysis identified many candidate drugs, some of which are already being investigated for treatment of COVID-19 and can serve as a basis for prioritizing additional viable candidate drugs for COVID-19.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32702730/
        doi: 10.21203/rs.3.rs-39128/v1

         id: cord-321267-ihd30qi0
     author: Daughton, Christian G.
      title: Natural experiment concept to accelerate the Re-purposing of existing therapeutics for Covid-19
       date: 2020-05-15
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: One of the many questions with respect to controlling the novel coronavirus pandemic is whether existing drugs can be re-purposed (re-positioned) for the prevention or treatment of Covid-19 - or for any future epidemic. The usefulness of existing approaches for re-purposing range from computational modeling to clinical trials. These are often time-consuming, resource intensive, and prone to failure. Proposed here is a new but simple concept that would capitalize on the opportunity presented by the on-going natural experiment involving the collection of data from epidemiological surveillance screening and diagnostic testing for clinical treatment. The objective would be to also collect for each Covid-19 case the patient's prior usage of existing therapeutic drugs. These drug usage data would be collected for several major test groups - those who test positive for active SARS-CoV-2 infection (using molecular methods) and those who test negative for current infection but also test positive for past infection (using serologic antibody tests). Patients from each of these groups would also be categorized with respect to where they resided on the spectrum of morbidities (from no or mild symptomology to severe). By comparing the distribution of normalized usage data for each drug within each group, drugs that are more associated with particular test groups could be revealed as having potential prophylactic, therapeutic, or contraindicated effects with respect to disease progression. These drugs could then be selected as candidates for further evaluation in fighting Covid-19. Also summarized are some of the numerous attributes, advantages, and limitations of the proposed concept, all pointing to the need for further discussion and evaluation.
        url: https://www.sciencedirect.com/science/article/pii/S2590113320300109?v=s5
        doi: 10.1016/j.gloepi.2020.100026

         id: cord-288026-vcp8o5xn
     author: DeStefano, Vincent
      title: Applications of PLA in Modern Medicine
       date: 2020-09-06
      words: 8592.0
  sentences: 612.0
      pages: 
     flesch: 43.0
      cache: ./cache/cord-288026-vcp8o5xn.txt
        txt: ./txt/cord-288026-vcp8o5xn.txt
    summary: PLA has shown promise as a biomaterial in a plethora of healthcare applications such as tissue engineering or regenerative medicine, cardiovascular implants, dental niches, drug carriers, orthopedic interventions, cancer therapy, skin and tendon healing, and lastly medical tools / equipment. Blending with PLA-based stereocomplexed polymers, such as PLLA and PLDA, has demonstrated improved thermal stability and decelerated degradation rate. Manufacturing techniques may take advantage of the strong interactions between PDLA and PLLA blocks, which result from the formation of stereocomplex crystallization as well as improved mechanical properties and thermal stability. Degradation rate is dependent upon a number of factors: polymer composition, pH, device geometry, molecular weight, crystallinity, addition of drugs and/or additives, sterilization, mechanical stress, and fabrication processing. This is likely due to the controlled drug release and enhanced anti-tumor effects seen in doxorubicin-loaded PLA-based scaffolds, such as the one described by Niu et al. Effect of molecular weight and crystallinity on poly(lactic acid) mechanical properties
   abstract: Polylactic acid (PLA) is a versatile biopolymer. PLA is synthesized with ease from abundant renewable resources and is biodegradable. PLA has shown promise as a biomaterial in a plethora of healthcare applications such as tissue engineering or regenerative medicine, cardiovascular implants, dental niches, drug carriers, orthopedic interventions, cancer therapy, skin and tendon healing, and lastly medical tools / equipment. PLA has demonstrated instrumental importance as a three-dimensionally (3D) printable biopolymer, which has further been bolstered by its role during the Coronavirus Disease of 2019 (Covid-19) global pandemic. As an abundant filament, PLA has created desperately needed personal protective equipment (PPE) and ventilator modifications. As polymer chemistry continues to advance, so too will the applications and continued efficacy of PLA-based modalities.
        url: https://api.elsevier.com/content/article/pii/S2666138120300098
        doi: 10.1016/j.engreg.2020.08.002

         id: cord-322915-zrjx31ev
     author: Demain, Arnold L
      title: Microbial drug discovery: 80 years of progress
       date: 2009-01-09
      words: 11246.0
  sentences: 688.0
      pages: 
     flesch: 40.0
      cache: ./cache/cord-322915-zrjx31ev.txt
        txt: ./txt/cord-322915-zrjx31ev.txt
    summary: Evidence of the importance of natural products in the discovery of leads for the development of drugs for the treatment of human diseases is provided by the fact that close to half of the best selling pharmaceuticals in 1991 were either natural products or their derivatives. In addition to the antibiotic-resistance problem, new families of anti-infective compounds are needed to enter the marketplace at regular intervals to tackle the new diseases caused by evolving pathogens. 28 Among the novel class of antimicrobial agents used in treating resistance to Gram-positive infections, we can also mention the cyclic lipopeptide antibiotic daptomycin produced by Streptomyces roseosporus. 44 Other applications include antitumor drugs, enzyme inhibitors, gastrointestinal motor stimulator agents, hypocholesterolemic drugs, ruminant growth stimulants, insecticides, herbicides, coccidiostats, antiparasitics vs coccidia, helminths and other pharmacological activities. Considering that animal health research and the development of new anti-infective product discovery have decreased, the discovery of new antibiotics has decreased over the past 15 years, with few new drug approvals.
   abstract: Microbes have made a phenomenal contribution to the health and well-being of people throughout the world. In addition to producing many primary metabolites, such as amino acids, vitamins and nucleotides, they are capable of making secondary metabolites, which constitute half of the pharmaceuticals on the market today and provide agriculture with many essential products. This review centers on these beneficial secondary metabolites, the discovery of which goes back 80 years to the time when penicillin was discovered by Alexander Fleming.
        url: https://doi.org/10.1038/ja.2008.16
        doi: 10.1038/ja.2008.16

         id: cord-303555-mwu72q7w
     author: Dent, Paul
      title: Cell Signaling and Translational Developmental Therapeutics
       date: 2020-10-06
      words: 8877.0
  sentences: 556.0
      pages: 
     flesch: 49.0
      cache: ./cache/cord-303555-mwu72q7w.txt
        txt: ./txt/cord-303555-mwu72q7w.txt
    summary: Thus, by the mid-to late-1980s a large body of literature existed which argued that signal transduction pathways consisted of a receptor linked to a large GTP-binding protein which in turn regulated an enzyme that generated "second messengers;" the second messengers would then diffuse throughout the cytosol activating cellular processes, predominantly for metabolism. For the EGFR and other subsequently discovered membrane associated tyrosine kinases, e.g. the non-receptor SCR family and the fibroblast growth factor receptor (FGFR) family, understanding how these enzymes signaled into the cell again initially rested on studies using traditional biochemical methods. [71] [72] [73] [74] [75] [76] Contemporaneously with these studies, researchers were determining how receptor tyrosine kinases regulated RAS family small GTP binding proteins, and other groups determining how RAS proteins signaled downstream off the plasma membrane and into the cytosol.
   abstract: The relationships between drug pharmacodynamics and subsequent changes in cellular signaling processes are complex. Many in vitro cell signaling studies often use drug concentrations above physiologically safe drug levels achievable in a patient's plasma. Drug companies develop agents to inhibit or modify the activities of specific target enzymes, often without a full consideration that their compounds have additional unknown targets. These two negative sequelae, when published together, become impediments against successful developmental therapeutics and translation because this data distorts our understanding of signaling mechanisms and reduces the probability of successfully translating drug-based concepts from the bench to the bedside. This article will discuss cellular signaling in isolation and as it relates to extant single and combined therapeutic drug interventions. This will lead to a hypothetical series standardized sequential approaches describing a rigorous concept to drug development and clinical translation.
        url: https://www.sciencedirect.com/science/article/pii/B9780128204726000025
        doi: 10.1016/b978-0-12-820472-6.00002-5

         id: cord-017583-72mbsib7
     author: Devarajan, Padma V.
      title: Infectious Diseases: Need for Targeted Drug Delivery
       date: 2014-09-01
      words: 8877.0
  sentences: 531.0
      pages: 
     flesch: 32.0
      cache: ./cache/cord-017583-72mbsib7.txt
        txt: ./txt/cord-017583-72mbsib7.txt
    summary: The adaptive mechanisms of Mycobacterium tuberculosis to survive inside the macrophages are prevention of fusion of the phagosome with lysosomes by producing tryptophan-aspartate-containing coat protein (TACO). In case of Mycobacterium tuberculosis infection, alveolar macrophages (dust cells), along with dendritic cells engulf bacteria and exhibit innate as well as an adaptive immune response. Infection of macrophages leads to changes in the expression pattern of the concerned receptors, which can be exploited for targeted drug delivery employing nanocarriers. Table 3 .6 is a summary of the important receptors on macrophages and illustrative examples of ligands for the same that could play a role in designing targeted nanocarriers for infectious disease therapy. Targeted drug delivery to enhance effi cacy and shorten treatment duration in disseminated Mycobacterium avium infection in mi host factors infl uencing the preferential localization of sterically stabilized liposomes in klebsiella pneumoniae-infected rat lung tissue Targeted intracellular delivery of antituberculosis drugs to mycobacterium tuberculosis-infected macrophages via functionalized mesoporous silica nanoparticles
   abstract: Infectious diseases are a leading cause of death worldwide, with the constant fear of global epidemics. It is indeed an irony that the reticuloendothelial system (RES), the body’s major defence system, is the primary site for intracellular infections which are more difficult to treat. Pro-inflammatory M1 macrophages play an important role in defence. However, ingenious pathogen survival mechanisms including phagolysosome destruction enable their persistence. Microbial biofilms present additional challenges. Low intracellular drug concentrations, drug efflux by efflux pumps and/or enzymatic degradation, emergence of multi-drug resistance (MDR), are serious limitations of conventional therapy. Targeted delivery using nanocarriers, and passive and active targeting strategies could provide quantum increase in intracellular drug concentration. Receptor mediated endocytosis using appropriate ligands is a viable approach. Liposomes and polymeric/lipidic nanoparticles, dendrimers micelles and micro/nanoemulsions could all be relied upon. Specialised targeting approaches are demonstrated for important diseases like tuberculosis, HIV and Malaria. Application of targeted delivery in the treatment of veterinary infections is exemplified and future possibilities indicated. The chapter thus provides an overview on important aspects of infectious diseases and the challenges therein, while stressing on the promise of targeted drug delivery in augmenting therapy of infectious diseases.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122176/
        doi: 10.1007/978-3-319-11355-5_3

         id: cord-260215-gsnjlhjd
     author: Dhanani, Jayesh
      title: Fundamentals of aerosol therapy in critical care
       date: 2016-10-07
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Drug dosing in critically ill patients is challenging due to the altered drug pharmacokinetics–pharmacodynamics associated with systemic therapies. For many drug therapies, there is potential to use the respiratory system as an alternative route for drug delivery. Aerosol drug delivery can provide many advantages over conventional therapy. Given that respiratory diseases are the commonest causes of critical illness, use of aerosol therapy to provide high local drug concentrations with minimal systemic side effects makes this route an attractive option. To date, limited evidence has restricted its wider application. The efficacy of aerosol drug therapy depends on drug-related factors (particle size, molecular weight), device factors, patient-related factors (airway anatomy, inhalation patterns) and mechanical ventilation-related factors (humidification, airway). This review identifies the relevant factors which require attention for optimization of aerosol drug delivery that can achieve better drug concentrations at the target sites and potentially improve clinical outcomes.
        url: https://www.ncbi.nlm.nih.gov/pubmed/27716346/
        doi: 10.1186/s13054-016-1448-5

         id: cord-334881-x9nxxled
     author: Di Lorenzo, Giuseppe
      title: COVID 19 therapies and anti-cancer drugs: A systematic review of recent literature
       date: 2020-05-21
      words: 3248.0
  sentences: 186.0
      pages: 
     flesch: 45.0
      cache: ./cache/cord-334881-x9nxxled.txt
        txt: ./txt/cord-334881-x9nxxled.txt
    summary: BACKGROUND: It is reasonable to think that cancer patients undergoing chemotherapy, targeted therapy or immunotherapy could have a more aggressive course if positive for Coronavirus disease CoV-2 (COVID19). METHODS: We conducted a literature review on https://www.ncbi.nlm.nih.gov/pubmed/, https://scholar.google.com, www.arxiv.org, www.biorxiv.org, of all articles published using the keywords COVID-19 therapy or treatment and cancer until May 2, 2020. Sarilumab is an interleukin-6 (IL-6) receptor antagonist indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs) (53). AIFA has licensed a randomized phase 2 trial to evaluate the efficacy, safety and tolerability of J o u r n a l P r e -p r o o f baricitinib in addition to the usual treatment in patients with pneumonia in COVID-19 (Barcivid study) (74).
   abstract: BACKGROUND: It is reasonable to think that cancer patients undergoing chemotherapy, targeted therapy or immunotherapy could have a more aggressive course if positive for Coronavirus disease CoV-2 (COVID- 19). METHODS: We conducted a literature review on https://www.ncbi.nlm.nih.gov/pubmed/, https://scholar.google.com, www.arxiv.org, www.biorxiv.org, of all articles published using the keywords COVID-19 therapy or treatment and cancer until May 2, 2020. A total of 205 articles were identified and 53 were included in this review. RESULTS: We describe the ongoing COVID-19 therapies that should be known by oncologists and highlight the potential interactions with antineoplastic drugs, commonly used in clinical practice. The main drug interactions were found with tocilizumab, ruxolitinib and colchicine. Conclusions. The literature provides an inconclusive picture on potential preferred treatments for COVID-19 and their interactions with antineoplastic agents. Future clinical trials are needed to better understand the interactions between different drugs in the context of COVID-19 pandemic.
        url: https://doi.org/10.1016/j.critrevonc.2020.102991
        doi: 10.1016/j.critrevonc.2020.102991

         id: cord-018595-x3tleomb
     author: Dodiuk-Gad, Roni P.
      title: Adverse Medication Reactions
       date: 2017-04-25
      words: 16304.0
  sentences: 910.0
      pages: 
     flesch: 39.0
      cache: ./cache/cord-018595-x3tleomb.txt
        txt: ./txt/cord-018595-x3tleomb.txt
    summary: 2. Delayed-type drug hypersensitivity: Delayed-type drug hypersensitivity reactions usually take several days to weeks following drug exposure, with variable clinical presentations that may include Maculopapular Eruption (MPE), Fixed Drug Eruption (FDE), Acute Generalized Exanthematous Pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Examples of strong associations of HLA alleles with specific drug-induced hypersensitivity reactions include abacavir, nevirapine, carbamazepine, and allopurinol (Table 25. [61] , who reported the weak associations of HLA-A29, B12, and MPE maculopapular drug eruption, DRESS drug reaction with eosinophilia and systemic symptoms, SJS/TEN Stevens-Johnson syndrome/toxic epidermal necrolysis DR7 in sulfonamide-related TEN, and HLA-A2, B12 in oxicam-related TEN in Europeans [61] . Drug specific cytotoxic T-cells in the skin lesions of a patient with toxic epidermal necrolysis
   abstract: Cutaneous adverse drug reactions (ADRs) are among the most frequent adverse reactions in patients receiving drug therapy. They have a broad spectrum of clinical manifestations, are caused by various drugs, and result from different pathophysiological mechanisms. Hence, their diagnosis and management is challenging. Severe cutaneous ADRs comprise a group of diseases with major morbidity and mortality, reaching 30 % mortality rate in cases of Toxic Epidermal Necrolysis. This chapter covers the terminology, epidemiology, pathogenesis and classification of cutaneous ADR, describes the severe cutaneous ADRs and the clinical and laboratory approach to the patient with cutaneous ADR and presents the translation of laboratory-based discoveries on the genetic predisposition and pathogenesis of cutaneous ADRs to clinical management guidelines.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123512/
        doi: 10.1007/978-3-319-29785-9_25

         id: cord-298033-kzdp9edn
     author: Domingo, Esteban
      title: Quasispecies dynamics in disease prevention and control
       date: 2019-11-08
      words: 16346.0
  sentences: 735.0
      pages: 
     flesch: 37.0
      cache: ./cache/cord-298033-kzdp9edn.txt
        txt: ./txt/cord-298033-kzdp9edn.txt
    summary: Quasispecies dynamics in disease prevention and control following statement will be obvious to the reader: "If a single mutation is able to confer resistance to an antiviral agent, and the mutation does not cause a significant selective disadvantage to the virus (fitness decrease) in the considered environment, a drug-resistant virus mutant will be present in most, if not all, virus populations" (Domingo, 1989) . The phenotypic barrier to drug resistance is equivalent to the fitness cost inflicted upon the virus by the mutations and corresponding amino acid substitution(s) required for resistance [Fitness cost is treated in Chapter 4 (Section 4.6) and in Chapter 7 (Section 7.4.2) in connection with the frequency of monoclonal antibody-or cytotoxic T-cell-escape mutants in viral populations]. For viruses that replicate in cell culture, it is possible to estimate the minimal viral population size needed to select a drug-resistant mutant which is generally positively correlated with the genetic barrier ( Fig. 8.5 ).
   abstract: Medical interventions to prevent and treat viral disease constitute evolutionary forces that may modify the genetic composition of viral populations that replicate in an infected host and influence the genomic composition of those viruses that are transmitted and progress at the epidemiological level. Given the adaptive potential of viruses in general and the RNA viruses in particular, the selection of viral mutants that display some degree of resistance to inhibitors or vaccines is a tangible challenge. Mutant selection may jeopardize control of the viral disease. Strategies intended to minimize vaccination and treatment failures are proposed and justified based on fundamental features of viral dynamics explained in the preceding chapters. The recommended use of complex, multiepitopic vaccines, and combination therapies as early as possible after initiation of infection falls under the general concept that complexity cannot be combated with simplicity. It also follows that sociopolitical action to interrupt virus replication and spread as soon as possible is as important as scientifically sound treatment designs to control viral disease on a global scale.
        url: https://www.sciencedirect.com/science/article/pii/B9780128163313000088
        doi: 10.1016/b978-0-12-816331-3.00008-8

         id: cord-252147-bvtchcbt
     author: Domingo-Espín, Joan
      title: Engineered Biological Entities for Drug Delivery and Gene Therapy: Protein Nanoparticles
       date: 2011-11-15
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The development of genetic engineering techniques has speeded up the growth of the biotechnological industry, resulting in a significant increase in the number of recombinant protein products on the market. The deep knowledge of protein function, structure, biological interactions, and the possibility to design new polypeptides with desired biological activities have been the main factors involved in the increase of intensive research and preclinical and clinical approaches. Consequently, new biological entities with added value for innovative medicines such as increased stability, improved targeting, and reduced toxicity, among others have been obtained. Proteins are complex nanoparticles with sizes ranging from a few nanometers to a few hundred nanometers when complex supramolecular interactions occur, as for example, in viral capsids. However, even though protein production is a delicate process that imposes the use of sophisticated analytical methods and negative secondary effects have been detected in some cases as immune and inflammatory reactions, the great potential of biodegradable and tunable protein nanoparticles indicates that protein-based biotechnological products are expected to increase in the years to come.
        url: https://doi.org/10.1016/b978-0-12-416020-0.00006-1
        doi: 10.1016/b978-0-12-416020-0.00006-1

         id: cord-321657-2s1npse5
     author: Du, Sean Quan
      title: Mathematical modeling of interaction between innate and adaptive immune responses in COVID‐19 and implications for viral pathogenesis
       date: 2020-05-13
      words: 6461.0
  sentences: 294.0
      pages: 
     flesch: 59.0
      cache: ./cache/cord-321657-2s1npse5.txt
        txt: ./txt/cord-321657-2s1npse5.txt
    summary: 4 In this paper, we used mathematical modeling to investigate the dynamics of the viral infection/replication inside a human host, in particular, the influenza and the SARS-CoV-2 virus, as well as the interactions of target cells with the innate and AIRs. Our model suggests that most of the differences between the two types of infections can potentially be attributed to the timing mismatch between the two immune responses. More specifically, influenza is a very acute infection; all vulnerable cells are completely depleted and viruses are more or less cleared by the innate immune response, before the adaptive immune response (AIR), which has a transient nature, reaches a significant level. We proposed an immune-suppressing treatment based on the leanings of our modeling study, which is to apply immunosuppressive drugs during the early phase of infection to reduce the AIRs to a level low enough not to interfere with the innate immune response.
   abstract: We have applied mathematical modeling to investigate the infections of the ongoing coronavirus disease‐2019 (COVID‐19) pandemic caused by SARS‐CoV‐2 virus. We first validated our model using the well‐studied influenza viruses and then compared the pathogenesis processes between the two viruses. The interaction between host innate and adaptive immune responses was found to be a potential cause for the higher severity and mortality in COVID‐19 patients. Specifically, the timing mismatch between the two immune responses has a major impact on disease progression. The adaptive immune response of the COVID‐19 patients is more likely to come before the peak of viral load, while the opposite is true for influenza patients. This difference in timing causes delayed depletion of vulnerable epithelial cells in the lungs in COVID‐19 patients while enhancing viral clearance in influenza patients. Stronger adaptive immunity in COVID‐19 patients can potentially lead to longer recovery time and more severe secondary complications. Based on our analysis, delaying the onset of adaptive immune responses during the early phase of infections may be a potential treatment option for high‐risk COVID‐19 patients. Suppressing the adaptive immune response temporarily and avoiding its interference with the innate immune response may allow the innate immunity to more efficiently clear the virus.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32356908/
        doi: 10.1002/jmv.25866

         id: cord-322885-ob5euspo
     author: Durdagi, Serdar
      title: Near-Physiological-Temperature Serial Femtosecond X-ray Crystallography Reveals Novel Conformations of SARS-CoV-2 Main Protease Active Site for Improved Drug Repurposing
       date: 2020-09-09
      words: 10818.0
  sentences: 656.0
      pages: 
     flesch: 54.0
      cache: ./cache/cord-322885-ob5euspo.txt
        txt: ./txt/cord-322885-ob5euspo.txt
    summary: One Sentence Summary Radiation-damage-free high-resolution SARS-CoV-2 main protease SFX structures obtained at near-physiological-temperature offer invaluable information for immediate drug-repurposing studies for the treatment of COVID19. Radiation-damage-free SFX method which enables obtaining the novel high-resolution ambient-temperature structures of the binding pocket of Mpro provides an unprecedented opportunity for identification of highly effective inhibitors for drug repurposing by using a hybrid approach that combines structural and in silico methods. We determined two radiation-damage-free SFX crystal structures of SARS-CoV-2 Mpro in two crystal forms at 1.9 Å and 2.1 Å resolutions with the following PDB IDs: 7CWB and 7CWC, respectively (Fig. 1A, B) (Supplementary Table 1&2 The diffraction data collected remotely at the MFX instrument of the LCLS at SLAC National Laboratory, Menlo Park, CA (Sierra et al., They reveal novel active site residue conformations and dynamics at atomic level, revealing several differences compared to the prior ambient-temperature structure of SARS-CoV-2 Mpro that was obtained at a home X-ray source (Fig. 1A, B ).
   abstract: The COVID19 pandemic has resulted in 25+ million reported infections and nearly 850.000 deaths. Research to identify effective therapies for COVID19 includes: i) designing a vaccine as future protection; ii) structure-based drug design; and iii) identifying existing drugs to repurpose them as effective and immediate treatments. To assist in drug repurposing and design, we determined two apo structures of Severe Acute Respiratory Syndrome CoronaVirus-2 main protease at ambienttemperature by Serial Femtosecond X-ray crystallography. We employed detailed molecular simulations of selected known main protease inhibitors with the structures and compared binding modes and energies. The combined structural biology and molecular modeling studies not only reveal the dynamics of small molecules targeting main protease but will also provide invaluable opportunities for drug repurposing and structure-based drug design studies against SARS-CoV-2. One Sentence Summary Radiation-damage-free high-resolution SARS-CoV-2 main protease SFX structures obtained at near-physiological-temperature offer invaluable information for immediate drug-repurposing studies for the treatment of COVID19.
        url: https://doi.org/10.1101/2020.09.09.287987
        doi: 10.1101/2020.09.09.287987

         id: cord-353524-3w970ycx
     author: Dömling, Alexander
      title: Chemistry and Biology of SARS-CoV-2
       date: 2020-05-22
      words: 3942.0
  sentences: 237.0
      pages: 
     flesch: 52.0
      cache: ./cache/cord-353524-3w970ycx.txt
        txt: ./txt/cord-353524-3w970ycx.txt
    summary: Given that SARS-CoV-2 and SARS-CoV share very high identical sequence in their 3CLpro, these HIV protease inhibitors are currently again repurposed for the treatment of COVID-19 (Chinese Clinical Trial Registry: ChiCTR2000029539). 30, 31 The interplay of the ACE receptor in cardiovascular diseases (with the well-known drug class of ACE inhibitors) and as the docking point for SARS-CoV-2 cellular infection is a current point of intense debate and research. For example, the crystal structure of SARS-CoV-2 N protein RNA-binding domain was just published and will give structural insight as a potential drug target. Potential broad spectrum inhibitors of the coronavirus 3CLpro: A virtual screening and structure-based drug design study Severe acute respiratory syndrome coronavirus papain-like novel protease inhibitors: design, synthesis, protein-ligand X-ray structure and biological evaluation Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites
   abstract: SARS-CoV-2 (previously 2019-nCoV or Wuhan coronavirus) caused an unprecedented fast-spreading worldwide pandemic. Although currently with a rather low mortality rate, the virus spread rapidly over the world using the modern world’s traffic highways. The coronavirus (CoV) family members were responsible for several deadly outbreaks and epidemics during the last decade. Not only governments but also the scientific community reacted promptly to the outbreak, and information is shared quickly. For example, the genetic fingerprint was shared, and the 3D structure of key proteins was rapidly solved, which can be used for the discovery of potential treatments. An overview is given on the current knowledge of the spread, disease course, and molecular biology of SARS-CoV-2. We discuss potential treatment developments in the context of recent outbreaks, drug repurposing, and development timelines.
        url: https://www.sciencedirect.com/science/article/pii/S2451929420301959
        doi: 10.1016/j.chempr.2020.04.023

         id: cord-252166-qah877pk
     author: Ekins, S
      title: In silico pharmacology for drug discovery: applications to targets and beyond
       date: 2007-09-01
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Computational (in silico) methods have been developed and widely applied to pharmacology hypothesis development and testing. These in silico methods include databases, quantitative structure-activity relationships, similarity searching, pharmacophores, homology models and other molecular modeling, machine learning, data mining, network analysis tools and data analysis tools that use a computer. Such methods have seen frequent use in the discovery and optimization of novel molecules with affinity to a target, the clarification of absorption, distribution, metabolism, excretion and toxicity properties as well as physicochemical characterization. The first part of this review discussed the methods that have been used for virtual ligand and target-based screening and profiling to predict biological activity. The aim of this second part of the review is to illustrate some of the varied applications of in silico methods for pharmacology in terms of the targets addressed. We will also discuss some of the advantages and disadvantages of in silico methods with respect to in vitro and in vivo methods for pharmacology research. Our conclusion is that the in silico pharmacology paradigm is ongoing and presents a rich array of opportunities that will assist in expediating the discovery of new targets, and ultimately lead to compounds with predicted biological activity for these novel targets.
        url: https://www.ncbi.nlm.nih.gov/pubmed/17549046/
        doi: 10.1038/sj.bjp.0707306

         id: cord-299911-v95pf3eg
     author: El-Ghiaty, Mahmoud A.
      title: Cytochrome P450-mediated drug interactions in COVID-19 patients: current findings and possible mechanisms
       date: 2020-06-26
      words: 5319.0
  sentences: 272.0
      pages: 
     flesch: 37.0
      cache: ./cache/cord-299911-v95pf3eg.txt
        txt: ./txt/cord-299911-v95pf3eg.txt
    summary: Based on the conclusions drawn from the currently rapidly evolving knowledge about COVID-19, our hypothesis is built on the potential modulation of CYPs activity by the inflammatory environment provoked by SARS-CoV-2 infection, as well as the pathologic involvement of the liver which harbors the majority of the drug metabolizing enzymes (DMEs). Systemic inflammation and immune response represent a substantial element in many acute and chronic diseases which is strongly implicated in altering drug pharmacokinetics through, mainly, modulating the expression and activity of DMEs. As a main contributor to the metabolic biotransformation of most drugs, CYPs are widely involved in such disease-drug interactions [19] . For decades, IL-6 has been recognized as the major inflammatory element that provokes a significant repressive effect on the expression and activity of different CYPs. Human recombinant interleukin 6 (rhIL-6) has shown concentration-dependent blocking of phenobarbital-mediated induction of CYP2B1/2 mRNA and activity in rat hepatocytes [48] .
   abstract: At the end of 2019, the entire world has witnessed the birth of a new member of coronavirus family in Wuhan, China. Ever since, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has swiftly invaded every corner on the planet. By the end of April 2020, almost 3.5 million cases have been reported worldwide, with a death toll of about 250000 deaths. It is currently well-recognized that patient’s immune response plays a pivotal role in the pathogenesis of Coronavirus Disease 2019 (COVID-19). This inflammatory element was evidenced by its elevated mediators that, in severe cases, reach their peak in a cytokine storm. Together with the reported markers of liver injury, such hyperinflammatory state may trigger significant derangements in hepatic cytochrome P450 metabolic machinery, and subsequent modulation of drug clearance that may result in unexpected therapeutic/toxic response. We hypothesize that COVID-19 patients are potentially vulnerable to a significant disease-drug interaction, and therefore, suitable dosing guidelines with therapeutic drug monitoring should be implemented to assure optimal clinical outcomes.
        url: https://www.sciencedirect.com/science/article/pii/S0306987720311750?v=s5
        doi: 10.1016/j.mehy.2020.110033

         id: cord-334511-lx9608vy
     author: Emwas, Abdul-Hamid
      title: NMR as a “Gold Standard” Method in Drug Design and Discovery
       date: 2020-10-09
      words: 29224.0
  sentences: 1507.0
      pages: 
     flesch: 47.0
      cache: ./cache/cord-334511-lx9608vy.txt
        txt: ./txt/cord-334511-lx9608vy.txt
    summary: The nearly ubiquitous use of virtual screening is due to its efficiency in searching massive chemical databases in order to generate lead molecules [313] that inhibit protein-protein interactions [314] , and its ability to help identity ligand (drug) binding sites on the target of interest [310] to lend insight to the mechanisms of action for lead compounds [315, 316] . The nearly ubiquitous use of virtual screening is due to its efficiency in searching massive chemical databases in order to generate lead molecules [313] that inhibit protein-protein interactions [314] , and its ability to help identity ligand (drug) binding sites on the target of interest [310] to lend insight to the mechanisms of action for lead compounds [315, 316] . Clearly, combining virtual screening with NMR-based methods is advantageous in studying how ligands (drugs) bind and interact with targets (proteins) of interest. The interactions between targets (proteins) and ligands (small molecules) can be analyzed independently of the biological systems by using ''cell-based'' NMR drug design approaches.
   abstract: Studying disease models at the molecular level is vital for drug development in order to improve treatment and prevent a wide range of human pathologies. Microbial infections are still a major challenge because pathogens rapidly and continually evolve developing drug resistance. Cancer cells also change genetically, and current therapeutic techniques may be (or may become) ineffective in many cases. The pathology of many neurological diseases remains an enigma, and the exact etiology and underlying mechanisms are still largely unknown. Viral infections spread and develop much more quickly than does the corresponding research needed to prevent and combat these infections; the present and most relevant outbreak of SARS-CoV-2, which originated in Wuhan, China, illustrates the critical and immediate need to improve drug design and development techniques. Modern day drug discovery is a time-consuming, expensive process. Each new drug takes in excess of 10 years to develop and costs on average more than a billion US dollars. This demonstrates the need of a complete redesign or novel strategies. Nuclear Magnetic Resonance (NMR) has played a critical role in drug discovery ever since its introduction several decades ago. In just three decades, NMR has become a “gold standard” platform technology in medical and pharmacology studies. In this review, we present the major applications of NMR spectroscopy in medical drug discovery and development. The basic concepts, theories, and applications of the most commonly used NMR techniques are presented. We also summarize the advantages and limitations of the primary NMR methods in drug development.
        url: https://doi.org/10.3390/molecules25204597
        doi: 10.3390/molecules25204597

         id: cord-001244-qdld7hdc
     author: Fan, Yue-Nong
      title: iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking
       date: 2014-03-19
      words: 6502.0
  sentences: 339.0
      pages: 
     flesch: 46.0
      cache: ./cache/cord-001244-qdld7hdc.txt
        txt: ./txt/cord-001244-qdld7hdc.txt
    summary: In the predictor, the drug compound concerned was formulated by a 256-D (dimensional) vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine) algorithm. [59] did not provide a publicly accessible web-server for their method, and hence its practical application value is quite limited, particularly for the broad experimental scientists; (b) The prediction quality can be further enhanced by incorporating some key features into the formulation of NR-drug (nuclear receptor and drug) samples via the general form of pseudo amino acid composition [60] . Prediction of G-protein-coupled receptor classes based on the concept of Chou''s pseudo amino acid composition: An approach from discrete wavelet transform
   abstract: Nuclear receptors (NRs) are closely associated with various major diseases such as cancer, diabetes, inflammatory disease, and osteoporosis. Therefore, NRs have become a frequent target for drug development. During the process of developing drugs against these diseases by targeting NRs, we are often facing a problem: Given a NR and chemical compound, can we identify whether they are really in interaction with each other in a cell? To address this problem, a predictor called “iNR-Drug” was developed. In the predictor, the drug compound concerned was formulated by a 256-D (dimensional) vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine) algorithm. Compared with the existing prediction methods in this area, iNR-Drug not only can yield a higher success rate, but is also featured by a user-friendly web-server established at http://www.jci-bioinfo.cn/iNR-Drug/, which is particularly useful for most experimental scientists to obtain their desired data in a timely manner. It is anticipated that the iNR-Drug server may become a useful high throughput tool for both basic research and drug development, and that the current approach may be easily extended to study the interactions of drug with other targets as well.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975431/
        doi: 10.3390/ijms15034915

         id: cord-283287-073r80s7
     author: Farhoudian, Ali
      title: COVID-19 and Substance Use Disorders: Recommendations to a Comprehensive Healthcare Response. An International Society of Addiction Medicine Practice and Policy Interest Group Position Paper
       date: 2020-04-12
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Coronavirus Disease 2019 (COVID-19) is escalating all over the world and has higher morbidities and mortalities in certain vulnerable populations. People Who Use Drugs (PWUD) are a marginalized and stigmatized group with weaker immunity responses, vulnerability to stress, poor health conditions, high-risk behaviors, and lower access to health care services. These conditions put them at a higher risk of COVID-19 infection and its complications. In this paper, an international group of experts on addiction medicine, infectious diseases, and disaster psychiatry explore the possible raised concerns in this issue and provide recommendations to manage the comorbidity of COVID-19 and Substance Use Disorder (SUD).
        url: https://doi.org/10.32598/bcn.11.covid19.1
        doi: 10.32598/bcn.11.covid19.1

         id: cord-351517-npcuo1ld
     author: Gale, Robert Peter
      title: Liaisons Dangereuses? new drugs, physicians and the drug industry
       date: 2020-07-01
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pubmed/32612254/
        doi: 10.1038/s41409-020-0988-0

         id: cord-261170-arnwk287
     author: Gallimore, W.
      title: Chapter 18 Marine Metabolites Oceans of Opportunity
       date: 2017-12-31
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Abstract The marine environment provides an array of compounds often with unique molecular architectures boasting an equally wide array of bioactivities including anticancer, antiinflammatory, and antimicrobial activity. Typically without the benefit of folklore therapeutic knowledge, marine organisms are collected, extracted, and fractionated to afford compounds that undergo evaluation with in vivo and in vitro assays en route to clinical applications. The pharmaceutical industry has benefited from research into marine metabolites with the development of marine-derived drugs including cytarabine, vidarabine, and ziconotide along with the more recently developed formulation Carragelose, an antiviral spray. Cosmetic applications incorporating marine extracts include Abyssine and RefirMAR. Research with macroinvertebrates, macroalgae, and microorganisms continue in the hope that drugs of the future will be culled from the oceans of the world. While obtaining a consistent and adequate supply of the bioactive compounds remains a challenge to be overcome, synthetic methods are being employed along with the application of biotechnological techniques to ensure that the drugs, when developed, will be in sufficient quantities for distribution to those who are in need.
        url: https://api.elsevier.com/content/article/pii/B9780128021040000184
        doi: 10.1016/b978-0-12-802104-0.00018-4

         id: cord-017702-v46ye328
     author: Ganguly, Nirmal Kumar
      title: Pharmacogenomics and Personalized Medicine for Infectious Diseases
       date: 2013-06-11
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Humans have been plagued by the scourge of invasion by pathogens leading to infectious diseases from the time in memoriam and are still the cause of morbidity and mortality among millions of individuals. Trying to understand the disease mechanisms and finding the remedial measures have been the quest of humankind. The susceptibility to disease of an individual in a given population is determined by ones genetic buildup. Response to treatment and the disease prognosis also depends upon individual’s genetic predisposition. The environmental stress induces mutations and is leading to the emergence of ever-increasing more dreaded infectious pathogens, and now we are in the era of increasing antibiotic resistance that has thrown up a challenge to find new treatment regimes. Discoveries in the science of high-throughput sequencing and array technologies have shown new hope and are bringing a revolution in human health. The information gained from sequencing of both human and pathogen genomes is a way forward in deciphering host-pathogen interactions. Deciphering the pathogen virulence factors, host susceptibility genes, and the molecular programs involved in the pathogenesis of disease has paved the way for discovery of new molecular targets for drugs, diagnostic markers, and vaccines. The genomic diversity in the human population leads to differences in host responses to drugs and vaccines and is the cause of poor response to treatment as well as adverse reactions. The study of pharmacogenomics of infectious diseases is still at an early stage of development, and many intricacies of the host-pathogen interaction are yet to be understood in full measure. However, progress has been made over the decades of research in some of the important infectious diseases revealing how the host genetic polymorphisms of drug-metabolizing enzymes and transporters affect the bioavailability of the drugs which further determine the efficacy and toxicology of the drugs used for treatment. Further, the field of structural biology and chemistry has intertwined to give rise to medical structural genomics leading the way to the discovery of new drug targets against infectious diseases. This chapter explores how the advent of “omics” technologies is making a beginning in bringing about a change in the prevention, diagnosis, and treatments of the infectious diseases and hence paving way for personalized medicine.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122342/
        doi: 10.1007/978-81-322-1184-6_27

         id: cord-329881-9vnz5zzg
     author: Garcia, Sònia
      title: Pandemics and Traditional Plant-Based Remedies. A Historical-Botanical Review in the Era of COVID19
       date: 2020-08-28
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Pandemics are as old as humanity and since ancient times we have turned to plants to find solutions to health-related problems. Traditional medicines based mostly on plants are still the only therapeutic possibility in many developing countries, but even in the richest ones, herbal formulation currently receives increased attention. Plants are natural laboratories whose complex secondary metabolism produces a wealth of chemical compounds, leading to drug discovery – 25% of widespread use drugs are indeed of plant origin. Their therapeutic potential is even bigger: although many plant-based compounds show inhibitory effects against a myriad of pathogens, few reach the stage of clinical trials. Their mechanism of action is often unknown, yet traditional plant-based remedies have the advantage of a long-term experience in their use, usually of hundreds to thousands of years, and thus a precious experience on their safety and effects. Here I am providing a non-systematic historical-botanical review of some of the most devastating pandemics that humanity has faced, with a focus on plant therapeutic uses. I will revisit the Middle Ages black death, in which a plant-based lotion (the four thieves vinegar) showed some effectiveness; the smallpox, a viral disease that lead to the discovery of vaccination but for which the native Americans had a plant ally, an interesting carnivorous plant species; tuberculosis and the use of garlic; the Spanish flu and the widespread recommendation of eating onions, among other plant-based treatments; and malaria, whose first effective treatment, quinine, came from the bark of a Peruvian tree, properties already known by the Quechua people. Synthetic analogues of quinine such as chloroquine or hydroxychloroquine are now being revisited for the treatment of COVID19 symptoms, as they are artemisinin and derivatives, other plant-based compounds effective against malaria. Finally, I will give some hints on another facet of plants to aid us in the prevention of infectious diseases: the production of biotechnological plant-based vaccines. Altogether, my aim is to stress the significant role of plants in global health (past, present and future) and the need of enhancing and protecting the botanical knowledge, from systematics to conservation, from ecology to ethnobotany.
        url: https://doi.org/10.3389/fpls.2020.571042
        doi: 10.3389/fpls.2020.571042

         id: cord-284479-75zgljet
     author: García-Serradilla, Moisés
      title: Drug repurposing for new, efficient, broad spectrum antivirals
       date: 2019-04-15
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Emerging viruses are a major threat to human health. Recent outbreaks have emphasized the urgent need for new antiviral treatments. For several pathogenic viruses, considerable efforts have focused on vaccine development. However, during epidemics infected individuals need to be treated urgently. High-throughput screening of clinically tested compounds provides a rapid means to identify undiscovered, antiviral functions for well-characterized therapeutics. Repurposed drugs can bypass part of the early cost and time needed for validation and authorization. In this review we describe recent efforts to find broad spectrum antivirals through drug repurposing. We have chosen several candidates and propose strategies to understand their mechanism of action and to determine how resistance to antivirals develops in infected cells.
        url: https://doi.org/10.1016/j.virusres.2019.02.011
        doi: 10.1016/j.virusres.2019.02.011

         id: cord-325473-hrdanbn1
     author: Ghahremanpour, Mohammad M.
      title: Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2
       date: 2020-08-28
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: A consensus virtual screening protocol has been applied to ca. 2000 approved drugs to seek inhibitors of the main protease (Mpro) of SARS-CoV-2, the virus responsible for COVID-19. 42 drugs emerged as top candidates, and after visual analyses of the predicted structures of their complexes with Mpro, 17 were chosen for evaluation in a kinetic assay for Mpro inhibition. Remarkably 14 of the compounds at 100-μM concentration were found to reduce the enzymatic activity and 5 provided IC50 values below 40 μM: manidipine (4.8 μM), boceprevir (5.4 μM), lercanidipine (16.2 μM), bedaquiline (18.7 μM), and efonidipine (38.5 μM). Structural analyses reveal a common cloverleaf pattern for the binding of the active compounds to the P1, P1’, and P2 pockets of Mpro. Further study of the most active compounds in the context of COVID-19 therapy is warranted, while all of the active compounds may provide a foundation for lead optimization to deliver valuable chemotherapeutics to combat the pandemic.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32869018/
        doi: 10.1101/2020.08.28.271957

         id: cord-257344-d13at1y5
     author: Ghasemiyeh, Parisa
      title: COVID-19 Outbreak: Challenges in Pharmacotherapy Based on Pharmacokinetic and Pharmacodynamic Aspects of Drug Therapy in Patients with Moderate to Severe Infection
       date: 2020-09-18
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: The new coronavirus (COVID-19) was first detected in Wuhan city of China in December 2019. Most patients infected with COVID-19 had clinical presentations of dry cough, fever, dyspnea, chest pain, fatigue and malaise, pneumonia, and bilateral infiltration in chest CT. Soon COVID-19 was spread around the world and became a pandemic. Now many patients around the world are suffering from this disease. Patients with predisposing diseases are highly prone to COVID-19 and manifesting severe infection especially with organ function damage such as acute respiratory distress syndrome, acute kidney injury, septic shock, ventilator-associated pneumonia, and death. Till now many drugs have been considered in the treatment of COVID-19 pneumonia, but pharmacotherapy in elderly patients and patients with pre-existing comorbidities is highly challenging. In this review, different potential drugs which have been considered in COVID-19 treatment have been discussed in detail. Also, challenges in the pharmacotherapy of COVID-19 pneumonia in patients with the underlying disease have been considered based on pharmacokinetic and pharmacodynamic aspects of these drugs.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32980626/
        doi: 10.1016/j.hrtlng.2020.08.025

         id: cord-303865-vd3qr32o
     author: Gianturco, Stephanie L.
      title: Outsourcing facilities and their place in the U.S. drug supply chain
       date: 2020-08-28
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: OBJECTIVE: The purpose of this commentary is to describe the ideal role of 503B outsourcing facilities in the U.S. drug supply chain. We also address the challenges that 503B outsourcing facilities are facing that limit their utilization and offer possible solutions. SUMMARY: Section 503B outsourcing facilities are emerging contributors in compounding owing to their ability to compound large quantities of medication without requiring patient-specific prescriptions. As such, they play a valuable role in the U.S. drug supply chain. The use of outsourcing facilities to compound ready-to-use drug products is gaining traction in hospitals and other health care systems. Outsourcing facilities help hospitals that are facing time and cost constraints owing to the evolving regulatory landscape around compounding. Although outsourcing facilities are assets to the drug supply chain, there are several challenges to their use. The lack of a finalized 503B Bulks List has led to outsourcing facilities being overly cautious in compounding products using bulk drug substances. In addition, the time between Food and Drug Administration (FDA) inspections is undefined, and a lack of follow-up information regarding concerns identified during an inspection may result in uncertainties about the current state of the outsourcing facility. CONCLUSIONS: Health care providers, outsourcing facilities, and FDA need to work together to ensure that patients are provided the drugs they need in a safe and effective way.
        url: https://doi.org/10.1016/j.japh.2020.07.021
        doi: 10.1016/j.japh.2020.07.021

         id: cord-007511-5d5authn
     author: Gil, JP
      title: CYP2C8 and antimalaria drug efficacy
       date: 2007-02-07
      words: 6628.0
  sentences: 363.0
      pages: 
     flesch: 47.0
      cache: ./cache/cord-007511-5d5authn.txt
        txt: ./txt/cord-007511-5d5authn.txt
    summary: By combining it with published in vitro pharmacodynamic and drug metabolism information, we review and predict the possible relevance, or lack of, of CYP2C8 polymorphisms in the present and future efficacy of amodiaquine. By combining it with published in vitro pharmacodynamic and drug metabolism information, we review and predict the possible relevance, or lack of, of CYP2C8 polymorphisms in the present and future efficacy of amodiaquine. This leaves drug therapy as the main tool for the global treatment and control of the disease, presently in the successful shape of the highly effective combination of artemisinine (ART) derivatives with longer half-life partners [4] .
   abstract: Malaria is a major infectious disease. In the last 10 years it has killed more than 20 million people, mainly small children in Africa. The highly efficacious artemisinine combination therapy is being launched globally, constituting the main hope for fighting the disease. Amodiaquine is a main partner in these combinations. Amodiaquine is almost entirely metabolized by the polymorphic cytochrome P450 (CYP) isoform 2C8 to the pharmacologically active desethylamodiaquine. The question remains whether the efficacy of amodiaquine is affected by the gene polymorphism. Genotype-inferred low metabolizers are found in 1–4% of African populations, which corresponds to millions of expected exposures to the drug. In vivo pharmacokinetic data on amodiaquine is limited. By combining it with published in vitro pharmacodynamic and drug metabolism information, we review and predict the possible relevance, or lack of, of CYP2C8 polymorphisms in the present and future efficacy of amodiaquine. Chloroquine and dapsone, both substrates of CYP2C8, are also discussed in the same context.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117598/
        doi: 10.2217/14622416.8.2.187

         id: cord-257144-3q0un5rl
     author: Giri, Allan
      title: Mutagenic, Genotoxic and Immunomodulatory effects of Hydroxychloroquine and Chloroquine: a review to evaluate its potential to use as a prophylactic drug against COVID-19
       date: 2020-09-02
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Hydroxychloroquine (HCQ) and Chloroquine (CQ) are two anti-malarial drugs that are now being extensively used by front-line healthcare workers and other common people as a prophylactic drug against the Corona Virus Disease − 19 (COVID-19) in India and as well as in many parts of the world. While only a few in vitro studies have pointed to some efficacy of these drugs as a prophylactic against COVID-19, to date, there are no clinical studies that have established any clinical efficacy of these drugs as a prophylactic. These drugs are commonly used for the treatment of Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) because of its immunomodulatory effects. Previously, we have evaluated the genetic toxicology of different drugs and chemicals including antimalarial drug CQ both in vitro and in vivo. Thus, we recognize the need to critically review the mutagenic, genotoxic, and immunomodulatory effects of these drugs, to find out whether it is safe to use as a prophylactic drug against COVID-19. Existing literature suggests that CQ can induce mutagenic and genotoxic effects in multiple test systems and both the drugs have immunomodulatory effects. There was no data available to evaluate the mutagenicity and genotoxicity for HCQ. However, during metabolism about 60% of both the drugs remain unchanged and about 40% of the drugs are metabolized into two metabolites, desethylchloroquine and bisdesethylchloroquine by the action of the cytochrome P450 (CYP) enzymes in the liver. Both HCQ and CQ are immunomodulatory drugs and have the potential to suppress normal immune system activation. In this review, we have elucidated the mechanism of immunomodulation by both HCQ and CQ and highlighted the mutagenic and genotoxic effects from the available literature. This article is written with the sole objective that the reader will be able to recognize the adverse effects of these drugs when consumed by healthy individuals as a prophylactic. Current literature indicates that healthy individuals should refrain from the use of these drugs until further investigation.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32884603/
        doi: 10.1186/s41021-020-00164-0

         id: cord-355971-99mhacqa
     author: Gougis, Paul
      title: Anticancer drugs and COVID-19 antiviral treatments in cancer patients: what can we safely use?
       date: 2020-06-10
      words: 761.0
  sentences: 63.0
      pages: 
     flesch: 38.0
      cache: ./cache/cord-355971-99mhacqa.txt
        txt: ./txt/cord-355971-99mhacqa.txt
    summary: title: Anticancer drugs and COVID-19 antiviral treatments in cancer patients: what can we safely use? • More safety data is needed to treat COVID-19 symptomatic patients with anticancer drugs known to increase infections. • A ready-to-use table synthetize these pharmacokinetic and pharmacodynamic interactions between antiviral and anticancer drugs. 1 In any of these settings, clinical trials and incoming standard of care could lead to the prescription of antiviral drugs concomitant to non-immunosuppressive anticancer treatments. Favipiravir, an anti-EBOV drug, also a candidate for the COVID-19 treatment, is an inhibitor of CYP2C8, 3 and therefore may increase anticancer drug metabolized through this pathway, such as dabrafenib and enzalutamide. The table (part B) summarizes pharmacokinetic and pharmacodynamics interactions between some currently tested drugs against COVID-19 and anticancer drugs. Orange boxes are for anticancer drugs prolonging QT without known Torsade-de-Pointes risk and moderate risk for renal and liver toxicities.
   abstract: • More safety data is needed to treat COVID-19 symptomatic patients with anticancer drugs known to increase infections. • We summarized immunosuppressing anticancer drugs; other drugs were studied for drug-drug interactions with antiviral medicines. • A ready-to-use table synthetize these pharmacokinetic and pharmacodynamic interactions between antiviral and anticancer drugs.
        url: https://doi.org/10.1016/j.ejca.2020.05.027
        doi: 10.1016/j.ejca.2020.05.027

         id: cord-022082-1dq623oe
     author: Greaves, Peter
      title: Respiratory Tract
       date: 2007-09-28
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The chapter describes different aspects of the respiratory tract. In preclinical safety studies, pathologies of the respiratory system can be a result of an intercurrent disease or can be induced by systemically administered drugs. Intranasal or inhalation modes of therapy pose particular challenges in terms of the formulations and technologies required to administer a drug. A complex technology is developed to support the assessment of adverse effects of inhaled substances in rodent and nonrodent species, and the extrapolation of experimental findings to humans. The nasal chambers are the structures that are first to be subjected to the effects of inhaled substances, whether microorganisms or chemical substances. In rodents, the relatively small size of the nose and nasal sinuses facilitates a histological examination. Findings show that infectious agents cause inflammation in the nose and nasal sinuses, and this may be associated with inflammation in the conjunctiva, the middle ear, and the oral cavity. It has been observed that a particular response of the rodent nasal mucosa to some irritant substances, including pharmaceutical agents, is the formation of rounded eosinophilic inclusions in the cytoplasm of sustentacular cells of the olfactory epithelium, and to a lesser extent in respiratory and glandular epithelial cells.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152448/
        doi: 10.1016/b978-044452771-4/50007-9

         id: cord-320172-qw47pf9r
     author: Greaves, Peter
      title: VII Digestive System 1
       date: 2000-12-31
      words: 47375.0
  sentences: 2238.0
      pages: 
     flesch: 40.0
      cache: ./cache/cord-320172-qw47pf9r.txt
        txt: ./txt/cord-320172-qw47pf9r.txt
    summary: In common with other changes induced in the digestive tract of rats and cynomolgus monkeys by the administration of recombinant human epidermal growth factor, the tongue showed squamous epithelial hyperplasia characterised by a uniform increase in the thickness of the squamous epithelium in both species (Breider et al., 1996; Reindel et al., 1996) . Detailed study of hypertrophy, protein synthesis, and intracellular cAMP activity in the salivary glands of rats treated for 10 days with isoprenaline (isoproterenol), a series of β-adrenergic receptor agonists and the phosphodiesterase inhibitors, theophylline and caffeine, showed that similar effects occurred with all agents although differences in the degree of hypertrophy, the nature of pro-tein and glycoprotein synthesis and Golgi membrane enzyme activity were recorded (Wells and Humphreys-Beher, 1985) . Studies in the rat have shown that diffuse atrophy of the gastric glands characterised by a decrease in the number and size of parietal, chief and mucous cells occurs transiently following truncal vagotomy but histological features return to normal by about 1 month after surgery (Nakamura, 1985) .
   abstract: Publisher Summary This chapter deals with the digestive system. The major and minor salivary glands and their secretions also represent and integral part of the protective mechanism of the oral cavity, and derangement of saliva production may lead to loss of integrity of the oral mucosa. Drug-induced abnormalities of taste sensation are also well-described phenomena occurring in man although human studies are necessary for the detection of these effects. Inflammation of the oral cavity may involve the buccal mucosa, the gingiva (gingivitis), the tongue (glossitis), and the peridontal tissues (peridontitis). Therapeutic agents can induce inflammatory lesions in the tongue. Moreover, a protective layer of mucus, a visco-elastic material containing high molecular weight glycoproteins produced by the major and minor salivary glands, covers the stratified squamous mucosa of the oral cavity. Salivary secretions also possess digestive enzyme activity although in herbivores and carnivores, it is usually low in contrast to high digestive enzyme activity in omnivorous species.
        url: https://api.elsevier.com/content/article/pii/B9780444505149500073
        doi: 10.1016/b978-044450514-9/50007-3

         id: cord-299225-exbdg3x9
     author: Guarnieri, Michael
      title: A Long-Term Study of a Lipid-Buprenorphine Implant in Rats
       date: 2018-07-09
      words: 2662.0
  sentences: 159.0
      pages: 
     flesch: 50.0
      cache: ./cache/cord-299225-exbdg3x9.txt
        txt: ./txt/cord-299225-exbdg3x9.txt
    summary: These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery in laboratory animals and suggest that this model may be used to study long-term effects of opiate therapy. We examined the safety of cholesterol-triglyceride suspensions of buprenorphine in mice and rats using US Food and Drug Administration (FDA) Target Animal Safety (TAS) drug-development protocols. Histopathology examinations were performed on mice and rats treated with up to tenfold excess of the intended dose of drug and control animals following 4-and 12-day drug trials [19] [20] [21] . The label dose of 0.65 mg/kg of buprenorphine, which provides 2-3 days of clinically significant blood levels of drug, was established in bioequivalence trials and efficacy studies using male and female rats [21] . The objective of this study was to evaluate the long-term safety of a lipid suspension of buprenorphine for delivery of an opiate analgesic in female F344 rats.
   abstract: Animal models to study opiates are of growing interest. We have examined the short-term safety of buprenorphine implants in Fischer F344/NTac rats treated with excess doses of a cholesterol-triglyceride suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of analgesia for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Here we report the results of a long-term follow-up study of female rats injected with 0.65 and 1.3 mg/kg. The 14-month evaluation showed no abnormal findings that could be attributed to the drug or lipid suspension. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery in laboratory animals and suggest that this model may be used to study long-term effects of opiate therapy.
        url: https://www.ncbi.nlm.nih.gov/pubmed/30112418/
        doi: 10.1155/2018/2616152

         id: cord-324660-w81jgw7p
     author: Guharoy, Roy
      title: Medication Shortages: A Matter of National Security—Time for Action
       date: 2020-08-01
      words: 1105.0
  sentences: 56.0
      pages: 
     flesch: 47.0
      cache: ./cache/cord-324660-w81jgw7p.txt
        txt: ./txt/cord-324660-w81jgw7p.txt
    summary: To the Editor: As noted by Choo and Rajkumar 1 in the June 2020 issue of Mayo Clinic Proceedings, the COVID-19 (coronavirus disease 19) pandemic has exposed extreme vulnerabilities in our nation''s drug supply chain. d Create a national database for tracking of essential drug supplies and use predictive analytics to identify surge, production problems, and future shortages. 1 As supply chain management leaders at Mayo Clinic, we appreciate the attention these authors draw towards the issue of drug shortages and drug costs. 5 Because of the high use of vasopressin in critically ill COVID-19 patients and the greater than 6000% price increase that has occurred after completing the Unapproved Drugs Initiative process, vasopressin will likely become a top 10 drug expense within the hospital sector by the end of 2020. The FDA Unapproved Drugs Initiative: an observational study of the consequences for drug prices and shortages in the United States
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pubmed/32753158/
        doi: 10.1016/j.mayocp.2020.06.025

         id: cord-203191-7ftg6bfx
     author: Guo, Kai
      title: Identification of Repurposal Drugs and Adverse Drug Reactions for Various Courses of Coronavirus Disease 2019 (COVID-19) Based on Single-cell RNA Sequencing Data
       date: 2020-05-16
      words: 3729.0
  sentences: 184.0
      pages: 
     flesch: 43.0
      cache: ./cache/cord-203191-7ftg6bfx.txt
        txt: ./txt/cord-203191-7ftg6bfx.txt
    summary: title: Identification of Repurposal Drugs and Adverse Drug Reactions for Various Courses of Coronavirus Disease 2019 (COVID-19) Based on Single-cell RNA Sequencing Data To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.S. FDA approved drugs and pre-clinical small-molecule compounds by integrating the gene expression perturbation data by chemicals from the Library of Integrated Network-Based Cellular Signatures (LINCS) project with publically available single-cell RNA sequencing dataset from mild and severe COVID-19 patients. We also collected a list of differentially expressed genes (DEGs) in SARS-CoV-2-infected lung BALF using a bulk RNA-Seq analysis to compare against the single-cell-based data. Repurposing analysis in severe COVID-19 patients 60 potent drugs were also selected in severe cases compared to controls (severe vs healthy group) according to their average CS between the replicates, and 25 of them involved in more than one cell subtype ( Figure 2B , Supplementary Tables S8 & S9) .
   abstract: With more than 3.8 million people infected Coronavirus Disease 2019 (COVID-19), caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a critical threat to human health. There is no proven vaccine or specific drug to date, which highlights the urgent need for rapid development of therapeutics for COVID-19. To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.S. FDA approved drugs and pre-clinical small-molecule compounds by integrating the gene expression perturbation data by chemicals from the Library of Integrated Network-Based Cellular Signatures (LINCS) project with publically available single-cell RNA sequencing dataset from mild and severe COVID-19 patients. We identified 281 FDA approved drugs that have the potential to be effective against SARS-CoV-2 infection, 10 of which are currently undergoing clinical trials to evaluate their efficacy against COVID-19. In conclusion, we have identified a list of repurposable anti-SARS- CoV-2 drugs using a systems biology approach.
        url: https://arxiv.org/pdf/2005.07856v1.pdf
        doi: nan

         id: cord-329318-eo8auo1f
     author: Gusarov, Sergey
      title: COSMO-RS-Based Descriptors for the Machine Learning-Enabled Screening of Nucleotide Analogue Drugs against SARS-CoV-2
       date: 2020-10-26
      words: 3971.0
  sentences: 217.0
      pages: 
     flesch: 46.0
      cache: ./cache/cord-329318-eo8auo1f.txt
        txt: ./txt/cord-329318-eo8auo1f.txt
    summary: [Image: see text] Chemical similarity-based approaches employed to repurpose or develop new treatments for emerging diseases, such as COVID-19, correlates molecular structure-based descriptors of drugs with those of a physiological counterpart or clinical phenotype. In this study, we propose a novel set of drug screening descriptors based on COSMO-RS σ-profiles, augmented by dipole moment and induced charge of the phosphorus atom, to evaluate the chemical similarity of the drugs with nucleotides, as RNA replication transcription initiation activators. A novel set of descriptors based on COSMO-RS σ-profiles and chemical thermodynamics is proposed and evaluated using PCA for the initial screening of a series of nucleotides and nucleotide-analog RdRp replication inhibitor drugs to help accelerate the discovery of COVID-19 treatments. The PCA results show that the novel σ-profile-based descriptor set I clearly correlates the leading COVID-19 drugs remdesivir and EIDD-2801 in monophosphate forms and highlights weaker correlations with drugs that have been reported to exhibit anti-SARS-CoV-2 activity.
   abstract: [Image: see text] Chemical similarity-based approaches employed to repurpose or develop new treatments for emerging diseases, such as COVID-19, correlates molecular structure-based descriptors of drugs with those of a physiological counterpart or clinical phenotype. We propose novel descriptors based on a COSMO-RS (short for conductor-like screening model for real solvents) σ-profiles for enhanced drug screening enabled by machine learning (ML). The descriptors’ performance is hereby illustrated for nucleotide analogue drugs that inhibit the ribonucleic acid-dependent ribonucleic acid polymerase, key to viral transcription and genome replication. The COSMO-RS-based descriptors account for both chemical reactivity and structure, and are more effective for ML-based screening than fingerprints based on molecular structure and simple physical/chemical properties. The descriptors are evaluated using principal component analysis, an unsupervised ML technique. Our results correlate with the active monophosphate forms of the leading drug remdesivir and the prospective drug EIDD-2801 with nucleotides, followed by other promising drugs, and are superior to those from molecular structure-based descriptors and molecular docking. The COSMO-RS-based descriptors could help accelerate drug discovery for the treatment of emerging diseases.
        url: https://doi.org/10.1021/acs.jpclett.0c02836
        doi: 10.1021/acs.jpclett.0c02836

         id: cord-255895-6at9gelt
     author: Han, Namshik
      title: Identification of SARS-CoV-2 induced pathways reveal drug repurposing strategies
       date: 2020-08-25
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The global outbreak of SARS-CoV-2 necessitates the rapid development of new therapies against COVID-19 infection. Here, we present the identification of 200 approved drugs, appropriate for repurposing against COVID-19. We constructed a SARS-CoV-2-induced protein (SIP) network, based on disease signatures defined by COVID-19 multi-omic datasets(Bojkova et al., 2020; Gordon et al., 2020), and cross-examined these pathways against approved drugs. This analysis identified 200 drugs predicted to target SARS-CoV-2-induced pathways, 40 of which are already in COVID-19 clinical trials(Clinicaltrials.gov, 2020) testifying to the validity of the approach. Using artificial neural network analysis we classified these 200 drugs into 9 distinct pathways, within two overarching mechanisms of action (MoAs): viral replication (130) and immune response (70). A subset of drugs implicated in viral replication were tested in cellular assays and two (proguanil and sulfasalazine) were shown to inhibit replication. This unbiased and validated analysis opens new avenues for the rapid repurposing of approved drugs into clinical trials.
        url: https://doi.org/10.1101/2020.08.24.265496
        doi: 10.1101/2020.08.24.265496

         id: cord-016283-b6yywn9f
     author: Hasan, Ashfaq
      title: Clinical Aspects and Principles of Management of Tuberculosis
       date: 2019-08-07
      words: 6930.0
  sentences: 347.0
      pages: 
     flesch: 46.0
      cache: ./cache/cord-016283-b6yywn9f.txt
        txt: ./txt/cord-016283-b6yywn9f.txt
    summary: Notwithstanding the advances in modern science, clinical diagnosis sometimes remains elusive, owing principally to the frequent paucibacillary occurrence of the disease and the slow doubling time of the organism; empiric treatment is often fraught with risks in the era of increasing drug resistance. The line probe assays (LPA) can permit rapid identification of specific gene markers associated with rifampicin resistance alone or in combination with isoniazid, and provide clinically relevant information about the level of INH resistance (low level associated with the INH-A gene; versus high level associated with the kat-G gene) (WHO treatment guidance for drug resistant tuberculosis 2016). Anti-tubercular drugs require to be supplemented with carefully monitored steroid therapy in two circumstances: tubercular meningitis (a short course of dexamethasone or prednisolone is typically given, tapered over 6 to 8 weeks) and tuberculous pericarditis (Guidelines for treatment of drug-susceptible tuberculosis and patient care 2017).
   abstract: Tuberculosis over the ages, has killed more people than any other infection has. Notwithstanding the advances in modern science, clinical diagnosis sometimes remains elusive, owing principally to the frequent paucibacillary occurrence of the disease and the slow doubling time of the organism; empiric treatment is often fraught with risks in the era of increasing drug resistance. This chapter attempts to provide an overview of the disease, beginning with the pathogenesis and its protean clinical presentations. It also discusses the recent evolution of molecular methods that have lately provided an impetus to early diagnosis with a clear opportunity to unmask drug resistance before initiating “blind”, potentially ineffective, and sometimes harmful treatment with standard therapy. The chapter also provides insight into tuberculosis in special situations, and discusses briefly the treatments in uncomplicated cases as well as in special situations, and in instances of drug resistance. Preventive methods including current and upcoming vaccines are mentioned. Finally, a short discussion of the sequelae of tuberculosis—which have the potential to be confused with active disease—is presented.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120521/
        doi: 10.1007/978-981-32-9413-4_20

         id: cord-000182-ni6iyzdn
     author: He, Zhisong
      title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features
       date: 2010-03-11
      words: 6037.0
  sentences: 305.0
      pages: 
     flesch: 46.0
      cache: ./cache/cord-000182-ni6iyzdn.txt
        txt: ./txt/cord-000182-ni6iyzdn.txt
    summary: title: Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features Many researchers have made lots of efforts to develop useful algorithms and softwares to investigate various drug-related biological problems, such as HIV protease cleavage site prediction [18, 19] , identification of GPCR (G protein-coupled receptors) type [20, 21] , protein signal peptide prediction [22] , protein subcellular location prediction [23, 24, 25] , analysis of specificity of GalNAc-transferase protein [26] , identification of protease type [27, 28] , membrane protein type prediction [29, 30, 31, 32] , and a series of relevant webserver predictors as summarized in a recent review [33] . The drug-target benchmark datasets thus obtained for enzymes, ion-channels, GPCRs, and nuclear receptors are given in Online Supporting Information S1, S2, S3, and S4, respectively. Prediction of G-protein-coupled receptor classes based on the concept of Chou''s pseudo amino acid composition: an approach from discrete wavelet transform
   abstract: BACKGROUND: Study of drug-target interaction networks is an important topic for drug development. It is both time-consuming and costly to determine compound-protein interactions or potential drug-target interactions by experiments alone. As a complement, the in silico prediction methods can provide us with very useful information in a timely manner. METHODS/PRINCIPAL FINDINGS: To realize this, drug compounds are encoded with functional groups and proteins encoded by biological features including biochemical and physicochemical properties. The optimal feature selection procedures are adopted by means of the mRMR (Maximum Relevance Minimum Redundancy) method. Instead of classifying the proteins as a whole family, target proteins are divided into four groups: enzymes, ion channels, G-protein- coupled receptors and nuclear receptors. Thus, four independent predictors are established using the Nearest Neighbor algorithm as their operation engine, with each to predict the interactions between drugs and one of the four protein groups. As a result, the overall success rates by the jackknife cross-validation tests achieved with the four predictors are 85.48%, 80.78%, 78.49%, and 85.66%, respectively. CONCLUSION/SIGNIFICANCE: Our results indicate that the network prediction system thus established is quite promising and encouraging.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836373/
        doi: 10.1371/journal.pone.0009603

         id: cord-316792-89f8g0m8
     author: Herzig, Volker
      title: Animal toxins — Nature’s evolutionary-refined toolkit for basic research and drug discovery
       date: 2020-06-12
      words: 12747.0
  sentences: 631.0
      pages: 
     flesch: 42.0
      cache: ./cache/cord-316792-89f8g0m8.txt
        txt: ./txt/cord-316792-89f8g0m8.txt
    summary: Over the course of evolution, toxins with exceptional specificity and high potency for their intended molecular targets have prevailed, making venoms an invaluable and almost inexhaustible source of bioactive molecules, some of which have found use as pharmacological tools, human therapeutics, and bioinsecticides. Current biomedically-focused research on venoms is directed towards their use in delineating the physiological role of toxin molecular targets such as ion channels and receptors, studying or treating human diseases, targeting vectors of human diseases, and treating microbial and parasitic infections. Since many venoms and toxins exert these biological effects through actions on cell membranes, receptors and ion channels, high-throughput techniques assessing changes in cellular signalling have proven particularly insightful. Spider-venom peptides have been crucial for uncovering the key role of ASICs in stroke-induced brain damage, and validating these channels as a target for neuroprotective drugs [134] [135] [136] [137] .
   abstract: Venomous animals have evolved toxins that interfere with specific components of their victim’s core physiological systems, thereby causing biological dysfunction that aids in prey capture, defense against predators, or other roles such as intraspecific competition. Many animal lineages evolved venom systems independently, highlighting the success of this strategy. Over the course of evolution, toxins with exceptional specificity and high potency for their intended molecular targets have prevailed, making venoms an invaluable and almost inexhaustible source of bioactive molecules, some of which have found use as pharmacological tools, human therapeutics, and bioinsecticides. Current biomedically-focused research on venoms is directed towards their use in delineating the physiological role of toxin molecular targets such as ion channels and receptors, studying or treating human diseases, targeting vectors of human diseases, and treating microbial and parasitic infections. We provide examples of each of these areas of venom research, highlighting the potential that venom molecules hold for basic research and drug development.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32535105/
        doi: 10.1016/j.bcp.2020.114096

         id: cord-257496-mirh80gn
     author: Hickey, Anthony J.
      title: Emerging trends in inhaled drug delivery
       date: 2020-07-12
      words: 4689.0
  sentences: 258.0
      pages: 
     flesch: 42.0
      cache: ./cache/cord-257496-mirh80gn.txt
        txt: ./txt/cord-257496-mirh80gn.txt
    summary: These product variables in combination with patient variables, including co-ordination skill during inhaler use, intrinsic lung biology, disease and consequent pulmonary function, contribute to drug safety and efficacy outcomes. Figure 1 summarizes the requirements of matching the therapeutic agent to the desired treatment outcome while considering the overall host system barriers (deposition and clearance mechanisms) and target (receptor or pathogen) biology guiding selection or development of a suitable drug delivery technology. However, recently the use of liposomes to aid in drug preparation and delivery and to aid in targeting of macrophages has advanced formulation options [28, 29] .The use of ethanol in the solutions delivered from the Respimat™ soft mist inhaler, e.g. tiotropium (Spiriva®, Boehringer Ingelheim) enhances the solubilization properties of the medium and facilitates a hand held aqueous based system with accurate and reproducible performance in delivering very low doses (<10 µg) on a single breath analogous to a metered dose inhaler [30, 31] . The addition of low-density lipid particles to HFA as a dispersant for micronized drug has allowed for a range of new metered dose inhaler products to come to market [40] .
   abstract: Ideally, inhaled therapy is driven by the needs of specific disease management. Lung biology interfaces with inhaler performance to allow optimal delivery of therapeutic agent for disease treatment. Inhalation aerosol products consist of the therapeutic agent, formulation, and device. The manufacturing specifications on each of the components, and their combination, allow accurate and reproducible control of measures of quality and in-vitro performance. These product variables in combination with patient variables, including co-ordination skill during inhaler use, intrinsic lung biology, disease and consequent pulmonary function, contribute to drug safety and efficacy outcomes. Due to the complexity of pulmonary drug delivery, predicting biological outcomes from first principles has been challenging. Ongoing research appears to offer new insights that may allow accurate prediction of drug behavior in the lungs. Disruptive innovations were characteristic of research and development in inhaled drug delivery at the end of the last century. Although there were relatively few new inhaled products launched in the first decade of the new millennium it was evident that the earlier years of exploration resulted in maturation of commercially successful technologies. A significant increase in new and generic products has occurred in the last decade and technical, regulatory and disease management trends are emerging. Some of these developments can trace their origins to earlier periods of creativity in the field while others are a reflection of advances in other areas of basic and computer sciences and engineering. Select biological and technical advances are highlighted with reflections on the potential to impact future clinical and regulatory considerations.
        url: https://api.elsevier.com/content/article/pii/S0169409X2030082X
        doi: 10.1016/j.addr.2020.07.006

         id: cord-294582-flkjekyo
     author: Hijikata, Atsushi
      title: Knowledge‐based structural models of SARS‐CoV‐2 proteins and their complexes with potential drugs
       date: 2020-05-25
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID‐19) caused by the novel coronavirus SARS‐CoV‐2 a pandemic. There is, however, no confirmed anti‐COVID‐19 therapeutic currently. In order to assist structure‐based discovery efforts for repurposing drugs against this disease, we constructed knowledge‐based models of SARS‐CoV‐2 proteins and compared the ligand molecules in the template structures with approved/experimental drugs and components of natural medicines. Our theoretical models suggest several drugs, such as carfilzomib, sinefungin, tecadenoson, and trabodenoson, that could be further investigated for their potential for treating COVID‐19.
        url: https://doi.org/10.1002/1873-3468.13806
        doi: 10.1002/1873-3468.13806

         id: cord-104431-3rblzyry
     author: Hill, Andrew
      title: Minimum costs to manufacture new treatments for COVID-19
       date: 2020-04-30
      words: 5494.0
  sentences: 336.0
      pages: 
     flesch: 56.0
      cache: ./cache/cord-104431-3rblzyry.txt
        txt: ./txt/cord-104431-3rblzyry.txt
    summary: RESULTS: Minimum estimated costs of production were US $0.93/day for remdesivir, $1.45/day for favipiravir, $0.08/day for hydroxychloroquine, $0.02/day for chloroquine, $0.10/day for azithromycin, $0.28/day for lopinavir/ritonavir, $0.39/day for sofosbuvir/daclatasvir and $1.09/day for pirfenidone. large donor organisations such as the global Fund for aiDs, TB and Malaria (gFaTM) and the President''s emergency Plan for aiDs relief (PePFar) order drugs to treat >20 million people with hiV, at prices close to the cost of production [20, 21] . We used all available costing data for each drug aPi found on Panjiva, excluding shipments <1kg in size, alongside the lowest and highest 15% of results based on prices per kg. Minimum costs to manufacture new treatments for cOViD-19 67 Different dosing protocols are being used for hydroxychloroquine, including 600 mg daily in the small, open-label, non-randomised French study by gautret et al.
   abstract: INTRODUCTION: ‘Repurposing’ existing drugs to treat COVID-19 is vital to reducing mortality and controlling the pandemic. Several promising drugs have been identified and are in various stages of clinical trials globally. If efficacy of these drugs is demonstrated, rapid, mass availability at an affordable cost would be essential to ensuring equity and access especially amongst low- and middle-income economies. METHODS: Minimum costs of production were estimated from the costs of active pharmaceutical ingredients using established methodology, which had good predictive accuracy for medicines for hepatitis C and HIV amongst others. Data were extracted from global export shipment records or analysis of the route of chemical synthesis. The estimated costs were compared with list prices from a range of countries where pricing data were available. RESULTS: Minimum estimated costs of production were US $0.93/day for remdesivir, $1.45/day for favipiravir, $0.08/day for hydroxychloroquine, $0.02/day for chloroquine, $0.10/day for azithromycin, $0.28/day for lopinavir/ritonavir, $0.39/day for sofosbuvir/daclatasvir and $1.09/day for pirfenidone. Costs of production ranged between $0.30 and $31 per treatment course (10–28 days). Current prices of these drugs were far higher than the costs of production, particularly in the US. CONCLUSIONS: Should repurposed drugs demonstrate efficacy against COVID-19, they could be manufactured profitably at very low costs, for much less than current list prices. Estimations for the minimum production costs can strengthen price negotiations and help ensure affordable access to vital treatment for COVID-19 at low prices globally.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213074/
        doi: nan

         id: cord-280158-3fhhuzg5
     author: Hoffman, Paul S.
      title: Antibacterial Discovery: 21st Century Challenges
       date: 2020-04-28
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: It has been nearly 50 years since the golden age of antibiotic discovery (1945–1975) ended; yet, we still struggle to identify novel drug targets and to deliver new chemical classes of antibiotics to replace those rendered obsolete by drug resistance. Despite herculean efforts utilizing a wide range of antibiotic discovery platform strategies, including genomics, bioinformatics, systems biology and postgenomic approaches, success has been at best incremental. Obviously, finding new classes of antibiotics is really hard, so repeating the old strategies, while expecting different outcomes, seems to boarder on insanity. The key questions dealt with in this review include: (1) If mutation based drug resistance is the major challenge to any new antibiotic, is it possible to find drug targets and new chemical entities that can escape this outcome; (2) Is the number of novel chemical classes of antibacterials limited by the number of broad spectrum drug targets; and (3) If true, then should we focus efforts on subgroups of pathogens like Gram negative or positive bacteria only, anaerobic bacteria or other group where the range of common essential genes is likely greater?. This review also provides some examples of existing drug targets that appear to escape the specter of mutation based drug resistance, and provides examples of some intermediate spectrum strategies as well as modern molecular and genomic approaches likely to improve the odds of delivering 21st century medicines to combat multidrug resistant pathogens.
        url: https://doi.org/10.3390/antibiotics9050213
        doi: 10.3390/antibiotics9050213

         id: cord-001072-pjv3wy80
     author: Hong, Xiaoyun
      title: Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine
       date: 2013-09-04
      words: 4118.0
  sentences: 196.0
      pages: 
     flesch: 41.0
      cache: ./cache/cord-001072-pjv3wy80.txt
        txt: ./txt/cord-001072-pjv3wy80.txt
    summary: Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. 13, 14 Microneedles are mostly applied for the transdermal delivery of drugs and vaccines that may require long exposure, among which the dissolving and biodegradable microneedle technologies are most commonly seen. Microneedle technologies for sustained drug delivery has long been recognized as a highly immune reactive tissue containing an abundance of antigen-presenting cells and immunocompetent cells, especially within the epidermal and dermal skin layers. 36 DeMuth et al 37 reported an approach for rapid implantation of vaccine-loaded polymer films carrying DNA, immune-stimulatory RNA, and biodegradable polycations using microneedles coated with releasable polyelectrolyte multilayers that promoted local transfection and controlled the persistence of DNA and adjuvants in the skin from days to weeks, with kinetics determined by the film composition. 29, 35 Altogether, dissolving and biodegradable microneedle technologies have a bright future for transdermal sustained delivery of drug and vaccine, and require further studies.
   abstract: Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771849/
        doi: 10.2147/dddt.s44401

         id: cord-274401-pjyvg53w
     author: Hrkach, Jeff
      title: From micro to nano: evolution and impact of drug delivery in treating disease
       date: 2020-05-08
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Over the past 50 years, drug delivery breakthroughs have enabled the approval of several important medicines. Often, this path starts with innovation from academic collaborations amongst biologists, chemists, and engineers, followed by the formation of a start-up company driving clinical translation and approval. An early wave featured injectable (i.e., intramuscular, subcutaneous) biodegradable polymeric microspheres to control drug release profiles for peptides and small molecules (e.g., Lupron Depot®, Risperdal Consta®). With these early successes for microspheres, research shifted to exploring systemic delivery by intravenous injection, which required smaller particle sizes and modified surface properties (e.g., PEGylation) to enable long circulation times. These new innovations resulted in the nanoparticle medicines Doxil® and Abraxane®, designed to improve the therapeutic index of cytotoxic cancer agents by decreasing systemic exposure and delivering more drug to tumors. Very recently, the first siRNA lipid nanoparticle medicine, Patisiran (Onpattro®), was approved for treating hereditary transthyretin-mediated amyloidosis. In this inspirational note, we will highlight the technological evolution of drug delivery from micro- to nano-, citing some of the approved medicines demonstrating the significant impact of the drug delivery field in treating many diseases.
        url: https://doi.org/10.1007/s13346-020-00769-6
        doi: 10.1007/s13346-020-00769-6

         id: cord-268283-eja8fkwv
     author: Iftikhar, Hafsa
      title: Identification of potential inhibitors of three key enzymes of SARS-CoV2 using computational approach
       date: 2020-06-09
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: The recent outbreak of coronavirus disease-19 (COVID-19) continues to drastically affect healthcare throughout the world. To date, no approved treatment regimen or vaccine is available to effectively attenuate or prevent the infection. Therefore, collective and multidisciplinary efforts are needed to identify new therapeutics or to explore effectiveness of existing drugs and drug-like small molecules against SARS-CoV-2 for lead identification and repurposing prospects. This study addresses the identification of small molecules that specifically bind to any of the three essential proteins (RdRp, 3CL-protease and helicase) of SARS-CoV-2. By applying computational approaches we screened a library of 4574 compounds also containing FDA-approved drugs against these viral proteins. Shortlisted hits from initial screening were subjected to iterative docking with the respective proteins. Ranking score on the basis of binding energy, clustering score, shape complementarity and functional significance of the binding pocket was applied to identify the binding compounds. Finally, to minimize chances of false positives, we performed docking of the identified molecules with 100 irrelevant proteins of diverse classes thereby ruling out the non-specific binding. Three FDA-approved drugs showed binding to 3CL-protease either at the catalytic pocket or at an allosteric site related to functionally important dimer formation. A drug-like molecule showed binding to RdRp in its catalytic pocket blocking the key catalytic residues. Two other drug-like molecules showed specific interactions with helicase at a key domain involved in catalysis. This study provides lead drugs or drug-like molecules for further in vitro and clinical investigation for drug repurposing and new drug development prospects.
        url: https://www.sciencedirect.com/science/article/pii/S0010482520302079
        doi: 10.1016/j.compbiomed.2020.103848

         id: cord-257318-jejgkcql
     author: Jain, K.K.
      title: Synthetic Biology and Personalized Medicine
       date: 2012-08-16
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Synthetic biology, application of synthetic chemistry to biology, is a broad term that covers the engineering of biological systems with structures and functions not found in nature to process information, manipulate chemicals, produce energy, maintain cell environment and enhance human health. Synthetic biology devices contribute not only to improve our understanding of disease mechanisms, but also provide novel diagnostic tools. Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs. The potential of synthetic genome, using an expanded genetic code that is designed for specific drug synthesis as well as delivery and activation of the drug in vivo by a pathological signal, was already pointed out during a lecture delivered at Kuwait University in 2005. Of two approaches to synthetic biology, top-down and bottom-up, the latter is more relevant to the development of personalized medicines as it provides more flexibility in constructing a partially synthetic cell from basic building blocks for a desired task.
        url: https://doi.org/10.1159/000341794
        doi: 10.1159/000341794

         id: cord-275772-pmf6stua
     author: Jourdan, Jean‐Pierre
      title: Drug repositioning: a brief overview
       date: 2020-04-17
      words: 3239.0
  sentences: 160.0
      pages: 
     flesch: 43.0
      cache: ./cache/cord-275772-pmf6stua.txt
        txt: ./txt/cord-275772-pmf6stua.txt
    summary: Drug repositioning lies in repurposing an active pharmaceutical ingredient that is already on the market for a new indication. This original definition of drug repositioning has since been extended to include active substances that failed the clinical phase of their development on account of their toxicity or insufficient efficacy, as well as drugs withdrawn from the market because of safety concerns. Instead, repositioning makes use in a new indication of either the biological properties for which the drug has already been approved (possibly according to a different formulation, at a new dose or via a new route of administration), or the side properties of a drug that are responsible for its adverse effects. This example illustrates how even drugs with an exceptionally poor toxicity profile can be repositioned if the new indication is a rare disease (the estimated incidence of leprosy is 250 000 cases per year according to http://www.orpha.net, accessed November, 21th 2019). Drug repositioning: identifying and developing new uses for existing drugs
   abstract: OBJECTIVES: Drug repositioning, that is, the use of a drug in an indication other than the one for which it was initially marketed, is a growing trend. Its origins lie mainly in the attrition experienced in recent years in the field of new drug discovery. KEY FINDINGS: Despite some regulatory and economic challenges, drug repositioning offers many advantages, and a number of recent successes have confirmed both its public health benefits and its commercial value. The first examples of successful drug repositioning mainly came about through serendipity like acetylsalicylic acid, thalidomide, sildenafil or dimethylfumarate. CONCLUSION: The history of great‐repositioned drugs has given some solutions to various pathologies. Serendipity is not yet useful to find repositioning drugs. Drug repositioning is of growing interest. Nowadays, a more rational approach to the identification of drug candidates for repositioning is possible, especially using data mining.
        url: https://doi.org/10.1111/jphp.13273
        doi: 10.1111/jphp.13273

         id: cord-035236-7rfc73qb
     author: Karabasz, Alicja
      title: Biomedical Applications of Multifunctional Polymeric Nanocarriers: A Review of Current Literature
       date: 2020-11-06
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Polymeric nanomaterials have become a prominent area of research in the field of drug delivery. Their application in nanomedicine can improve bioavailability, pharmacokinetics, and, therefore, the effectiveness of various therapeutics or contrast agents. There are many studies for developing new polymeric nanocarriers; however, their clinical application is somewhat limited. In this review, we present new complex and multifunctional polymeric nanocarriers as promising and innovative diagnostic or therapeutic systems. Their multifunctionality, resulting from the unique chemical and biological properties of the polymers used, ensures better delivery, and a controlled, sequential release of many different therapeutics to the diseased tissue. We present a brief introduction of the classical formulation techniques and describe examples of multifunctional nanocarriers, whose biological assessment has been carried out at least in vitro. Most of them, however, also underwent evaluation in vivo on animal models. Selected polymeric nanocarriers were grouped depending on their medical application: anti-cancer drug nanocarriers, nanomaterials delivering compounds for cancer immunotherapy or regenerative medicine, components of vaccines nanomaterials used for topical application, and lifestyle diseases, ie, diabetes.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654520/
        doi: 10.2147/ijn.s231477

         id: cord-104493-yqf7tyo4
     author: Keshmiri Neghab, Hoda
      title: Nanoformulation-Based Antiviral Combination Therapy for Treatment of COVID-19
       date: 2020
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502165/
        doi: nan

         id: cord-278362-pwi48i20
     author: Khan, Abbas
      title: Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro)
       date: 2020-06-18
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The current coronavirus (SARS-COV-2) pandemic and phenomenal spread to every nook and cranny of the world has raised major apprehensions about the modern public health care system. So far as a result of this epidemic, 4,434,653 confirmed cases and 302,169 deaths are reported. The growing infection rate and death toll demand the use of all possible approaches to design novel drugs and vaccines to curb this disease. In this study, we combined drugs repurposing and virtual drug screening strategies to target 3CLpro, which has an essential role in viral maturation and replication. A total of 31 FDA approved anti-HIV drugs, and Traditional Chinese medicines (TCM) database were screened to find potential inhibitors. As a result, Saquinavir, and five drugs (TCM5280805, TCM5280445, TCM5280343, TCM5280863, and TCM5458190) from the TCM database were found as promising hits. Furthermore, results from molecular dynamics simulation and total binding free energy revealed that Saquinavir and TCM5280805 target the catalytic dyad (His41 and Cys145) and possess stable dynamics behavior. Thus, we suggest that these compounds should be tested experimentally against the SARS-COV-2 as Saquinavir has been reported to inhibit HIV protease experimentally. Considering the intensity of coronavirus dissemination, the present research is in line with the idea of discovering the latest inhibitors against the coronavirus essential pathways to accelerate the drug development cycle. Communicated by Ramaswamy H. Sarma.
        url: https://doi.org/10.1080/07391102.2020.1779128
        doi: 10.1080/07391102.2020.1779128

         id: cord-263874-q0egnzwf
     author: Khan, Md. Arif
      title: Comparative molecular investigation of the potential inhibitors against SARS-CoV-2 main protease: a molecular docking study
       date: 2020-07-22
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Recent outbreak of novel coronavirus and its rapid pandemic escalation in all over the world has drawn the attention to urgent need for effective drug development. However, due to prolonged vaccine and drug development procedure against a newly emerged devastating SARS-CoV-2 virus pathogen, repurposing of existing potential pertinent drug molecules would be preferable strategy to reduce mortality immediately and further development of new drugs to combat overall global Covid-19 crisis in all over the world. Herein, we have filtered 23 prospective drug candidates through literature review. Assessing evidences from molecular docking studies, it was clearly seen that, Epirubicin, Vapreotida, and Saquinavir exhibited better binding affinity against SARS-CoV-2 Main Protease than other drug molecules among the 23 potential inhibitors. However, 50 ns molecular dynamics simulation indicated the less mobile nature of the docked complex maintaining structural integrity. Our overall prediction findings indicate that Epirubicin, Vapreotida, and Saquinavir may inhibit COVID-19 by synergistic interactions in the active cavity and those results can pave the way in drug discovery although it has to be further validated by in-vitro and in-vivo investigations. Communicated by Ramaswamy H. Sarma
        url: https://www.ncbi.nlm.nih.gov/pubmed/32696718/
        doi: 10.1080/07391102.2020.1796813

         id: cord-273716-vv3pyft4
     author: Khosravi-Darani, Kianoush
      title: The role of high-resolution imaging in the evaluation of nanosystems for bioactive encapsulation and targeted nanotherapy
       date: 2007-07-03
      words: 10230.0
  sentences: 514.0
      pages: 
     flesch: 34.0
      cache: ./cache/cord-273716-vv3pyft4.txt
        txt: ./txt/cord-273716-vv3pyft4.txt
    summary: This review will focus on nanoscale bioactive delivery and targeting mechanisms and the role of high-resolution imaging techniques in the evaluation and development of nanocarriers. Applications of nanotechnology in medicine are particularly promising and areas such as molecular imaging, disease diagnosis, bioactive encapsulation and targeted delivery at specific sites in the body are being intensively investigated and some products undergoing clinical trials (Moghimi et al., 2005; Shaffer, 2005; Wilkinson, 2003) . Usefulness of high-resolution scanning probe imaging in the study of lipidic gene transfer vectors and the interaction between liposomes and DNA molecules have recently been reviewed by Mozafari et al. Modern nanocarrier systems such as nanoliposomes, niosomes, solid lipid nanoparticles (Saupe and Rades, 2006) , as well as silicon-, carbon-and polymer-based nanocarriers play an important role in controlled delivery of the bioactive agents to the desired site of action, limiting the side effects at nontarget sites (Ruozi et al., 2007) .
   abstract: Nanotechnology has already started to significantly impact many industries and scientific fields including biotechnology, pharmaceutics, food technology and semiconductors. Nanotechnology-based tools and devices, including high-resolution imaging techniques, enable characterization and manipulation of materials at the nanolevel and further elucidate nanoscale phenomena and equip us with the ability to fabricate novel materials and structures. One of the most promising impacts of nanotechnology is in the area of nanotherapy. Employing nanosystems such as dendrimers, nanoliposomes, niosomes, nanotubes, emulsions and quantum dots, nanotherapy leads toward the concept of personalized medicine and the potential for early diagnoses coupled with efficient targeted therapy. The development of smart targeted nanocarriers that can deliver bioactives at a controlled rate directly to the designated cells and tissues will provide better efficacy and reduced side effects. Nanocarriers improve the solubility of bioactives and allow for the delivery of not only small-molecule drugs but also the delivery of nucleic acids and proteins. This review will focus on nanoscale bioactive delivery and targeting mechanisms and the role of high-resolution imaging techniques in the evaluation and development of nanocarriers.
        url: https://api.elsevier.com/content/article/pii/S0968432807001023
        doi: 10.1016/j.micron.2007.06.009

         id: cord-302947-flgwxc57
     author: Kipshidze, Nicholas
      title: Targeted, Site-Specific, Delivery Vehicles of Therapeutics for COVID-19 Patients. Brief Review
       date: 2020-09-16
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Definitive pharmacological therapies for COVID-19 have yet to be identified. Several hundred trials are ongoing globally in the hope of a solution. However, nearly all treatments rely on systemic delivery but COVID-19 damages the lungs preferentially. The use of a targeted delivery approach is reviewed where engineered products are able to reach damaged lung tissue directly, which includes catheter-based and aerosol-based approaches. In this review we have outlined various target directed approaches which include microbubbles, extracellular vesicles including exosomes, adenosine nanoparticles, novel bio-objects, direct aerosol targeted pulmonary delivery and catheter-based drug delivery with reference to their relative effectiveness for the specific lesions. Currently several trials are ongoing to determine the effectiveness of such delivery systems alone and in conjunction with systemic therapies. Such approaches may prove to be very effective in the controlled and localized COVID-19 viral lesions in the lungs and potential sites. Moreover, localized delivery offered a safer delivery mode for such drugs which may have systemic adverse effects.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32936689/
        doi: 10.1177/1076029620954911

         id: cord-266294-ua22udlc
     author: Koch, Oliver
      title: 29 Antiviral drugs
       date: 2010-12-31
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Publisher Summary This chapter discusses the adverse effects of antiviral drugs used against cytomegalovirus, herpesviruses, hepatitis viruses, against HIV, and against influenza viruses. The cidofovir, drug active against cytomegalovirus, has been associated with bronchiolitis obliterans. Aciclovir and valaciclovir has been reported with renal insufficiency. Adefovir , a drug active against hepatitis viruses, is associated with the fall in creatinine clearance in patients with lamivudine-resistant HBe antigen (HBeAg)negative disease. Drugs active against HIV are comprehensively reviewed as in combination, nucleoside analogue reverse transcriptase inhibitors, nucleoside analogue reverse transcriptase inhibitors, and protease inhibitors. In a randomized controlled trial of indinavir, saquinavir and lopinavir in combination with low-dose ritonavir in 656 patients, median total cholesterol increased by 0.5 mmol/l in the patients with the highest minimum drug plasma concentrations. In patients with AIDS-associated AIDS dementia complex taking optimal stable background antiretroviral therapy including either abacavir or placebo, there was significantly more nausea in those who took abacavir.
        url: https://www.sciencedirect.com/science/article/pii/S0378608010320290
        doi: 10.1016/s0378-6080(10)32029-0

         id: cord-001151-mdej7nhj
     author: Kumar De, Amit
      title: Application of an Amine Functionalized Biopolymer in the Colonic Delivery of Glycyrrhizin: A Design and In Vivo Efficacy Study
       date: 2013-05-18
      words: 5109.0
  sentences: 271.0
      pages: 
     flesch: 51.0
      cache: ./cache/cord-001151-mdej7nhj.txt
        txt: ./txt/cord-001151-mdej7nhj.txt
    summary: The entrapment efficiency and in vitro drug release were studied in simulated gastric, intestinal, and colonic fluids containing rat cecal contents. The in vitro drug release study was carried out in simulated gastric fluid of pH 1.2, simulated intestinal fluid of pH 6.8, and simulated colonic fluid of pH 7.4 containing rat cecal contents under anaerobic conditions. The drug release studies from the microparticles were carried out in the simulated gastric fluid of pH 1.2, simulated intestinal fluid of pH 6.8, and simulated colonic fluid of pH 7.4 containing rat cecal contents [34, 35] . In the simulated colonic fluid containing rat cecal contents, the drug release was a bit more augmented with an initial burst release common for each of the designed The results predict the drug-polymer ratio to be the key factor for controlling the release.
   abstract: In our current study, a newer amine functionalized guar gum derivative was studied for its efficacy in colonic drug delivery. Glycyrrhizic acid mono-ammonium salt was used as the model drug. Drug-loaded microparticles were formulated by ionic crosslinking using sodium tripolyphosphate. The Scanning Electron Microscopic study revealed spherical particles of sizes from 4.9 ± 3.8 μm to 6.9 ± 3.9 μm. The FT-IR studies presented a possible interaction between the drug and the polymer. The drug was encapsulated in amorphous form as observed from the powder X-Ray Diffraction studies. A cumulative drug release study was carried out in simulated gastric, intestinal, and colonic fluids. The cumulative drug release studies presented a burst release followed by a sustained release of the drug in simulated colonic fluid containing rat cecal contents. The drug-polymer ratio was optimised using a 3(2) factorial design by taking the amounts of glycyrrhizic acid (X(1)) and guar gum alkyl amine (X(2)) as the independant variables. The percent cumulative drug release at 240 mins (Q(240)), 720 mins (Q(720)), and at 1,440 mins (Q(1440)) were considered as the dependant variables. The efficacy of the optimized formulation was studied in a 2,4,6-trinitrobenzene sulfonic acid-induced rat colitis model. The tissue’s nitric oxide, malondialdehyde, and myeloperoxidase activities were found to be much lower in the microparticle-treated group compared to free drug-treated group. The histology of the colonic tissue from the treated group of animals revealed almost no infiltration of inflammatory cells in the tissue for the microparticle-treated group of animals. The synthesized amine derivative of guar gum was found to be better in vitro with a better in vivo efficacy in the colonic delivery of glycyrrhizic acid monoammonium salt and can be considered as a newer modified biopolymer for colonic drug delivery.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867243/
        doi: 10.3797/scipharm.1301-14

         id: cord-324166-6ydn2bvy
     author: Kumar, Neeraj
      title: Antitussive noscapine and antiviral drug conjugates as arsenal against COVID-19: a comprehensive chemoinformatics analysis
       date: 2020-08-20
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Coronavirus pandemic has caused a vast number of deaths worldwide. Thus creating an urgent need to develop effective counteragents against novel coronavirus disease (COVID-19). Many antiviral drugs have been repurposed for treatment but implicated minimal recovery, which further advanced the need for clearer insights and innovation to derive effective therapeutics. Strategically, Noscapine, an approved antitussive drug with positive effects on lung linings may show favorable outcomes synergistically with antiviral drugs in trials. Hence, we have theoretically examined the combinatorial drug therapy by culminating the existing experimental results with in silico analyses. We employed the antitussive noscapine in conjugation with antiviral drugs (Chloroquine, Umifenovir, Hydroxychloroquine, Favlplravir and Galidesivir). We found that Noscapine-Hydroxychloroquine (Nos-Hcq) conjugate has strong binding affinity for the main protease (Mpro) of SARS-CoV-2, which performs key biological function in virus infection and progression. Nos-Hcq was analyzed through molecular dynamics simulation. The MD simulation for 100 ns affirmed the stable binding of conjugation unprecedentedly through RMSD and radius of gyration plots along with critical reaction coordinate binding free energy profile. Also, dynamical residue cross-correlation map with principal component analysis depicted the stable binding of Nos-Hcq conjugate to Mpro domains with optimal secondary structure statistics of complex dynamics. Also, we reveal the drugs with stable binding to major domains of Mpro can significantly improve the work profile of reaction coordinates, drug accession and inhibitory regulation of Mpro. The designed combinatorial therapy paves way for further prioritized in vitro and in vivo investigations for drug with robust binding against Mpro of SARS-CoV-2.
        url: https://doi.org/10.1080/07391102.2020.1808072
        doi: 10.1080/07391102.2020.1808072

         id: cord-275827-r86ygqmy
     author: Lapeyre-Mestre, Maryse
      title: Addictovigilance contribution during COVID-19 epidemic and lockdown in France
       date: 2020-06-23
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Abstract Addictovigilance is a safety monitoring targeted at substances with potential for abuse and dependence. This vigilance was involved during the period of COVID-19 epidemic due to the significant changes in access to drugs and psychological disruption caused by the pandemic and lockdown. This article aims to present the different steps implemented by the French Addictovigilance network in collaboration with the French Health authorities from March to May 2020, including monitoring of potential harmful events, and scientific communication. The first events were identified through the continuity of the networking between the French addictovigilance centres and their partners: community pharmacies, general practitioners, specialized structures and emergency wards. As soon as the lockdown began, first cases of overdoses (lethal or not) were reported with opioids, mainly with methadone, and other opioids (heroin, oxycodone, tramadol or antitussive codeine). Lockdown-related noteworthy events consisted in clinical cases or other relevant information for which lockdown clearly played an important role : among the many substances identified at least once, pregabalin, benzodiazepines, cannabis, cocaine and nitrous oxide were the most significant in terms of prevalence, seriousness or particularly specific to the lockdown context. Despite significant decrease in the activity and travel limited to vital needs, community pharmacies continued to identify falsified prescriptions in this period, highlighting an increase in suspicious requests for pregabalin, codeine and tramadol. In parallel, the French addictovigilance network continued its communications efforts in the period, issuing a newsletter on tramadol, a press release on methadone and naloxone, and participating in the COVID-19 frequently asked questions (FAQs) of the French Society of Pharmacology and Therapeutic website (https://sfpt-fr.org/covid19 ). COVID-19 epidemic has been an important challenge for addictovigilance, and has proved that this monitoring is highly essential for alerting health professionals and health authorities to points of vigilance in the field of psychoactive substances.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32660776/
        doi: 10.1016/j.therap.2020.06.006

         id: cord-349794-mhviub6e
     author: Le, Brian L.
      title: Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19
       date: 2020-10-23
      words: 3810.0
  sentences: 216.0
      pages: 
     flesch: 43.0
      cache: ./cache/cord-349794-mhviub6e.txt
        txt: ./txt/cord-349794-mhviub6e.txt
    summary: We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available data. By infecting human adenocarcinomic alveolar basal epithelial cells with SARS-CoV-2 and comparing to controls, the authors generated a list of 120 differentially expressed genes. Here, we applied our existing computational drug repositioning pipeline to identify drug profiles with significantly reversed differential gene expression compared to predicted inhibitors (including one tested in Calu-3) were incubated with SARS-CoV-2 infected human embryonic kidney 293T cells overexpressing ACE2 (293T-ACE2) with viral replication determined using an immunofluorescence-based assay. In this study, we applied our drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available RNA-seq data ( Figure 1 ). Here, we used a transcriptomics-based drug repositioning pipeline to predict therapeutic drug hits for three different input SARS-CoV-2 signatures, each of which came from distinct human cell or tissue origins.
   abstract: The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available data. We utilized three independent published studies to acquire or generate lists of differentially expressed genes between control and SARS-CoV-2-infected samples. Using a rank-based pattern matching strategy based on the Kolmogorov-Smirnov Statistic, the signatures were queried against drug profiles from Connectivity Map (CMap). We validated sixteen of our top predicted hits in live SARS-CoV-2 antiviral assays in either Calu-3 or 293T-ACE2 cells. Validation experiments in human cell lines showed that 11 of the 16 compounds tested to date (including clofazimine, haloperidol and others) had measurable antiviral activity against SARS-CoV-2. These initial results are encouraging as we continue to work towards a further analysis of these predicted drugs as potential therapeutics for the treatment of COVID-19.
        url: https://doi.org/10.1101/2020.10.23.352666
        doi: 10.1101/2020.10.23.352666

         id: cord-328559-2qvxw896
     author: LeSaint, Kathy T.
      title: Impact of Social Distancing on Individuals Who Use Drugs: Considerations for Emergency Department Providers
       date: 2020-08-18
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: The isolation that comes from social distancing during the COVID-19 pandemic can be particularly detrimental to the United States’ population of people who use drugs. People with substance use disorders may be at risk for return to use, exacerbation of existing mental health disorders, and risky drug practices. In this commentary, we review the risk to people who use drugs and how emergency department providers can best support these individuals during the unprecedented time of social distancing.
        url: https://doi.org/10.5811/westjem.2020.7.47896
        doi: 10.5811/westjem.2020.7.47896

         id: cord-347986-ds5hm731
     author: Lee, Paul J.
      title: Developing Infectious Disease Strategies for the Developing World
       date: 2007-01-26
      words: 4102.0
  sentences: 193.0
      pages: 
     flesch: 48.0
      cache: ./cache/cord-347986-ds5hm731.txt
        txt: ./txt/cord-347986-ds5hm731.txt
    summary: The neuraminidase inhibitors, oseltamivir and zanamivir, have in vitro activities against the human H5N1 isolates; however, recent data suggest that higher doses for longer periods may be required to be effective. Human immunodeficiency virus (HIV), Ebola virus, hantavirus pulmonary syndrome, monkey pox and multidrug-resistant Mycobacterium tuberculosis (MDR-TB), Severe Acute Respiratory Syndrome (SARS) associated coronavirus and avian influenza are examples of emerging infections. Through a discussion of avian influenza and MDR-TB, primarily, we will demonstrate the magnitude of the problems of infectious diseases in the developing world and discuss approaches that can be taken to in an attempt to monitor and contain these new threats as they emerge. In fact, a recent Cochrane review covering appropriate studies to address the problem of treating latent tuberculosis infection in people exposed to MDR-TB found there were no randomized controlled trials in the database that have assessed the effectiveness of treatment [11] .
   abstract: This chapter discusses various drugs for human influenza A (H5N1) and multidrug-resistant mycobacterium tuberculosis (MDR-TB). The H5N1 avian influenza does not presently meet the criteria of an antigenically shifted strain. It is presently an avian strain that has not undergone reassortment with a human strain and is not well adapted to humans. H5N1 isolates are resistant to the M2 inhibitors amantadine and rimantadine; these antivirals do not have a role for the treatment or prophylaxis against the strain. The neuraminidase inhibitors, oseltamivir and zanamivir, have in vitro activities against the human H5N1 isolates; however, recent data suggest that higher doses for longer periods may be required to be effective. Oseltamivir is an oral agent approved for prophylaxis and the treatment of influenza infections. Zanamivir is delivered topically to the respiratory tract with similar indications. The drugs discussed in the chapter for MDR-TB fall into three categories—quinolones, nitroimidazoles, and pyrroles. Drugs such as moxifloxacin are methoxyfluoroquinolones, which are already available and approved for the treatment of acute respiratory infections, such as community-acquired pneumonia, intra-abdominal infections, acute sinusitis, and skin infections. Gatifloxacin 5, is another methoxyfluoroquinolone that is in clinical development for tuberculosis treatment.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32287466/
        doi: 10.1016/s0065-7743(06)41018-6

         id: cord-272060-o0wx0add
     author: Li, Allen
      title: Drug-drug interactions affecting drug levels of direct oral anticoagulants in the real world: A systematic review()
       date: 2020-08-11
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: BACKGROUND: Direct oral anticoagulants (DOACs) have emerged as safe and effective alternatives to Vitamin-K antagonists for treatment and prevention of arterial and venous thrombosis. Due to their novelty, pharmacokinetic DOAC drug-drug interactions (DDIs) that result in clinical adverse events have not been well-documented. OBJECTIVE: This study aims to systematically review reported pharmacokinetic DDIs resulting in clinical adverse events through documented observational evidence to better inform clinicians in clinical practice. METHODS: A comprehensive literature review of EMBASE, MEDLINE, and Ovid HealthStar was conducted through March 10th, 2020. Two independent reviewers screened and extracted data from eligible articles according to pre-established inclusion and exclusion criteria. Articles reporting bleeding or thrombotic outcomes in non-controlled (observational) settings resulting from suggested pharmacokinetic DOAC DDIs were included. RESULTS: A total of 5567 citations were reviewed, of which 24 were included following data extraction. The majority were case reports (n = 21) documenting a single adverse event resulting from a suspected DOAC DDI, while the remaining papers were a case series (n = 1) and cohort studies (n = 2). The most commonly reported interacting drugs were amiodarone and ritonavir (bleeding), and phenobarbital, phenytoin, and carbamazepine (thrombosis). Bleeding events more often resulted from a combined mechanism (P-glycoprotein AND CYP3A4 inhibition), whereas thrombotic events resulted from either combined OR single P-glycoprotein/CYP3A4 induction. CONCLUSION: Current literature evaluating the real-world risk of DOAC DDIs is limited to few case reports and retrospective observational analyses. Clinicians are encouraged to continue to report suspected drug interactions resulting in adverse events.
        url: https://www.sciencedirect.com/science/article/pii/S0049384820304540?v=s5
        doi: 10.1016/j.thromres.2020.08.016

         id: cord-270622-aofva2ab
     author: Li, Qizhang
      title: Potential clinical drugs as covalent inhibitors of the priming proteases of the spike protein of SARS-CoV-2
       date: 2020-08-26
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: In less than eight months, the COVID-19 (coronavirus disease 2019) caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus has resulted in over 20,000,000 confirmed cases and over 700,000 deaths around the world. With the increasing worldwide spreading of this disease, the lack of effective drugs against SARS-CoV-2 infection makes the situation even more dangerous and unpredictable. Although many forces are speeding up to develop prevention and treatment therapeutics, it is unlikely that any de novo drugs will be available in months. Drug repurposing holds the promise to significantly save the time for drug development, since it could use existing clinic drugs to treat new diseases. Based on the “steric-clashes alleviating receptor (SCAR)” strategy developed in our lab recently, we screened the library of clinic and investigational drugs, and identified nine drugs that might be repurposed as covalent inhibitors of the priming proteases (cathepsin B, cathepsin L, and TMPRSS2) of the spike protein of SARS-CoV-2. Among these hits, five are known covalent inhibitors, and one is an anti-virus drug. Therefore, we hope our work would provide rational and timely help for developing anti-SARS-CoV-2 drugs.
        url: https://api.elsevier.com/content/article/pii/S200103702030369X
        doi: 10.1016/j.csbj.2020.08.016

         id: cord-354445-lnvc7mmf
     author: Lichtenstein, David
      title: 4 Cleaning and Disinfecting Gastrointestinal Endoscopy Equipment
       date: 2019-12-31
      words: 13656.0
  sentences: 833.0
      pages: 
     flesch: 39.0
      cache: ./cache/cord-354445-lnvc7mmf.txt
        txt: ./txt/cord-354445-lnvc7mmf.txt
    summary: Abstract Outbreaks of infection transmission due to contaminated flexible endoscopes have focused the attention of health care personnel, senior management, device manufacturers, and regulators on the need to improve the approach used to offer this valuable service. Salmonella is a serious primary pathogen, and Pseudomonas is ubiquitous in many water sources, and although both these pathogens have been associated most frequently with endoscopic transmission, they are both sensitive to multiple agents, including glutaraldehyde, and other HLDs. Transmission of bacterial pathogens from flexible endoscopes has been rare since the adoption of the current 2011 multisociety reprocessing guideline, 45, 160 with the exception of duodenoscope-related infections (discussed later). Society of Gastroenterology Nurses and Associates: Guideline for use of high level disinfectants & sterilants for reprocessing flexible gastrointestinal endoscopes Society of Gastroenterology Nurses and Associates: Guideline for use of high level disinfectants & sterilants for reprocessing flexible gastrointestinal endoscopes
   abstract: Abstract Outbreaks of infection transmission due to contaminated flexible endoscopes have focused the attention of health care personnel, senior management, device manufacturers, and regulators on the need to improve the approach used to offer this valuable service. This chapter presents the principles of flexible endoscope reprocessing along with a pragmatic approach to the judicious selection and proper reprocessing of endoscopic equipment, as well as guidance for prevention and management of infection transmission inclusive of newer sterilization (e.g., hydrogen peroxide vapor) and disinfection (e.g., improved hydrogen peroxide) technologies. It also provides an outline of the Quality Systems approach that is applicable to flexible endoscope reprocessing and the need for ongoing staff competency and audits of endoscope cleaning, disinfection, and storage practices. Furthermore, the most current regulatory, expert organization, and manufacturer's recommendations are reviewed.
        url: https://www.sciencedirect.com/science/article/pii/B9780323415095000049
        doi: 10.1016/b978-0-323-41509-5.00004-9

         id: cord-291180-xurmzmwj
     author: Lin, Xiaoqian
      title: A Review on Applications of Computational Methods in Drug Screening and Design
       date: 2020-03-18
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Drug development is one of the most significant processes in the pharmaceutical industry. Various computational methods have dramatically reduced the time and cost of drug discovery. In this review, we firstly discussed roles of multiscale biomolecular simulations in identifying drug binding sites on the target macromolecule and elucidating drug action mechanisms. Then, virtual screening methods (e.g., molecular docking, pharmacophore modeling, and QSAR) as well as structure- and ligand-based classical/de novo drug design were introduced and discussed. Last, we explored the development of machine learning methods and their applications in aforementioned computational methods to speed up the drug discovery process. Also, several application examples of combining various methods was discussed. A combination of different methods to jointly solve the tough problem at different scales and dimensions will be an inevitable trend in drug screening and design.
        url: https://doi.org/10.3390/molecules25061375
        doi: 10.3390/molecules25061375

         id: cord-032561-x3qbqy69
     author: Liu, Gengqi
      title: Stimulus-Responsive Nanomedicines for Disease Diagnosis and Treatment
       date: 2020-09-02
      words: 25208.0
  sentences: 1664.0
      pages: 
     flesch: 46.0
      cache: ./cache/cord-032561-x3qbqy69.txt
        txt: ./txt/cord-032561-x3qbqy69.txt
    summary: demonstrated that nanodrug carriers with diselenides could release more drugs using poly (ester carbamate) triblock copolymers (PAUR-Se-Se) with Se-Se bonds compared with poly (ester carbamate) triblock copolymers (PAUR-S-S) [54, 55] Thioether Selenium Tellurium Besides the development of drug delivery systems, pH-responsive systems can also be used for tumor detection and image-guided surgery [46] . demonstrated that nanodrug carriers with diselenides could release more drugs using poly (ester carbamate) triblock copolymers (PAUR-Se-Se) with Se-Se bonds compared with poly (ester carbamate) triblock copolymers (PAUR-S-S) [65] PBA/PBE Besides the development of drug delivery systems, pH-responsive systems can also be used for tumor detection and image-guided surgery [46] . Therefore, pH responsive system can be combined with other stimulus conditions such as light, redox, enzymes and others with the aim of improved selectivity for drug release in diseased tissues [47, 48] . In addition to photothermal therapy and PDT, light-responsive strategies have also been applied in the design of prodrug systems and drug delivery carriers.
   abstract: Stimulus-responsive drug delivery systems generally aim to release the active pharmaceutical ingredient (API) in response to specific conditions and have recently been explored for disease treatments. These approaches can also be extended to molecular imaging to report on disease diagnosis and management. The stimuli used for activation are based on differences between the environment of the diseased or targeted sites, and normal tissues. Endogenous stimuli include pH, redox reactions, enzymatic activity, temperature and others. Exogenous site-specific stimuli include the use of magnetic fields, light, ultrasound and others. These endogenous or exogenous stimuli lead to structural changes or cleavage of the cargo carrier, leading to release of the API. A wide variety of stimulus-responsive systems have been developed—responsive to both a single stimulus or multiple stimuli—and represent a theranostic tool for disease treatment. In this review, stimuli commonly used in the development of theranostic nanoplatforms are enumerated. An emphasis on chemical structure and property relationships is provided, aiming to focus on insights for the design of stimulus-responsive delivery systems. Several examples of theranostic applications of these stimulus-responsive nanomedicines are discussed.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504550/
        doi: 10.3390/ijms21176380

         id: cord-333381-wz70o9tt
     author: Liu, Shao
      title: Providing pharmacy services during the coronavirus pandemic
       date: 2020-03-28
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: The coronavirus disease 19 (COVID-19) is quickly spreading across China and globally. Pharmacy services are an important pillar in public health to prevent and contain the COVID-19 pandemic. Chinese pharmacists have acted swiftly in the public health response in China, such as drafting professional service guidance to pharmacists and pharmacies, establishing emergency drug formularies, monitoring and resolving drug shortages, establishing remote pharmacy services to prevent human-to-human infections, providing event-driven pharmaceutical care, educating the public on infection prevention and disease management, and participating in clinical trials and drug evaluation. This commentary reviews the unique needs of pharmacy services in the COVID-19 pandemic, and shares our experiences with the international pharmacy community in the response to these needs.
        url: https://doi.org/10.1007/s11096-020-01017-0
        doi: 10.1007/s11096-020-01017-0

         id: cord-330380-wnbyy1gk
     author: Liu, Tingting
      title: Applying high-performance computing in drug discovery and molecular simulation
       date: 2016-01-11
      words: 8570.0
  sentences: 411.0
      pages: 
     flesch: 38.0
      cache: ./cache/cord-330380-wnbyy1gk.txt
        txt: ./txt/cord-330380-wnbyy1gk.txt
    summary: With the improvement of high-performance technologies, HPC and supercomputers are being applied to an increasing number of emerging fields including deep learning, big data mining, computational finance, and precision medicine, with the expectation that it will accelerate innovation. A series of CDDD approaches based on the 3D structures of biological macromolecules (e.g. proteins and nucleic acids), such as the highthroughput virtual screening method, have greatly improved the efficiency of drug discovery. This review mainly focuses on the application of HPC to the field of drug discovery and molecular simulation at CAS in recent years, including several cases involving virtual screening (molecular docking), MD simulation, and protein folding. Taken together, our study not only demonstrated that the α-helix/β-sheet intermediate structures revealed by the aforementioned simulations could be used as a binding target for inhibitor design, but also provided new insights into the molecular events involved in the conformational transition of Aβ peptides in fibrillogenesis.
   abstract: In recent decades, high-performance computing (HPC) technologies and supercomputers in China have significantly advanced, resulting in remarkable achievements. Computational drug discovery and design, which is based on HPC and combines pharmaceutical chemistry and computational biology, has become a critical approach in drug research and development and is financially supported by the Chinese government. This approach has yielded a series of new algorithms in drug design, as well as new software and databases. This review mainly focuses on the application of HPC to the fields of drug discovery and molecular simulation at the Chinese Academy of Sciences, including virtual drug screening, molecular dynamics simulation, and protein folding. In addition, the potential future application of HPC in precision medicine is briefly discussed.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32288960/
        doi: 10.1093/nsr/nww003

         id: cord-299424-qy3lccjq
     author: MUBAGWA, Kanigula
      title: Chloroquine cardiac effects and toxicity.A short update.
       date: 2020-06-19
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: There is currently an increased interest in using the antimalarials chloroquine and hydroxychloroquine for the treatment of other diseases, including cancer and viral infections such as COVID-19. However, risks of cardiotoxic effects tend to limit their use. The effects of these drugs on the electrical and mechanical activities of the heart, as well as on the remodeling of the cardiac tissue are presented, and the underlying molecular and cellular mechanisms discussed. The drugs can have proarrhythmic as well as antiarrhythmic actions, resulting from their inhibition of ion channels, including voltage-dependent Na(+) and Ca(2+) channels, background and voltage-dependent K(+) channels, and pacemaker channels. The drugs also exert a vagolytic effect, due at least in part to a muscarinic receptor antagonist action. They also interfere with the normal autophagy flux, an effect which could aggravate ischemia/reperfusion injury or post-infarct remodeling. Most of the toxic effects occur at high concentrations, following prolonged drug administration or in the context of drug associations.
        url: https://api.elsevier.com/content/article/pii/S0924857920302272
        doi: 10.1016/j.ijantimicag.2020.106057

         id: cord-344934-m0q7rm6z
     author: Mahapatra, Sovesh
      title: Repurposing Therapeutics for COVID-19: Rapid Prediction of Commercially available drugs through Machine Learning and Docking
       date: 2020-04-07
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Background The outbreak of the novel coronavirus disease COVID 19, caused by the SARS-CoV-2 virus has spread rapidly around the globe during the past 3 months. As the virus infected cases and mortality rate of this disease is increasing exponentially, scientists and researchers all over the world are relentlessly working to understand this new virus along with possible treatment regimens by discovering active therapeutic agents and vaccines. So, there is an urgent requirement of new and effective medications that can treat the disease caused by SARS CoV 2. Methods and findings We perform the study of drugs that are already available in the market and being used for other diseases to accelerate clinical recovery, in other words repurposing of existing drugs. The vast complexity in drug design and protocols regarding clinical trials often prohibit developing various new drug combinations for this epidemic disease in a limited time. Recently, remarkable improvements in computational power coupled with advancements in Machine Learning (ML) technology have been utilized to revolutionize the drug development process. Consequently, a detailed study using ML for the repurposing of therapeutic agents is urgently required. Here, we report the ML model based on the Naive Bayes algorithm, which has an accuracy of around 73% to predict the drugs that could be used for the treatment of COVID-19. Our study predicts around ten FDA approved commercial drugs that can be used for repurposing. Among all, we suggest that the antiretroviral drug Atazanavir (DrugBank ID DB01072) would probably be one of the most effective drugs based on the selected criterions. Conclusions Our study can help clinical scientists in being more selective in identifying and testing the therapeutic agents for COVID 19 treatment. The ML based approach for drug discovery as reported here can be a futuristic smart drug designing strategy for community applications.
        url: https://doi.org/10.1101/2020.04.05.20054254
        doi: 10.1101/2020.04.05.20054254

         id: cord-274474-u2fdicgz
     author: Majumder, Joydeb
      title: Targeted Nanotherapeutics for Respiratory Diseases: Cancer, Fibrosis, and Coronavirus
       date: 2020-10-13
      words: 10098.0
  sentences: 634.0
      pages: 
     flesch: 46.0
      cache: ./cache/cord-274474-u2fdicgz.txt
        txt: ./txt/cord-274474-u2fdicgz.txt
    summary: The present review summarizes recent advances in the development of nanocarrier based therapeutics for local and targeted delivery of drugs, nucleic acids and imaging agents for diagnostics and treatment of various diseases such as cancer, cystic fibrosis, and coronavirus. [1, 2] Therefore, methods of developing new therapeutic solutions as well as improving the current therapies for the common lung diseases such as asthma, cystic fibrosis, chronic obstructive pulmonary disease, lung cancer, and coronavirus infections remain the main focus in the fields of targeted drug delivery. In this review, we will summarize recent reports on the development of lipid and polymer based nanocarriers for targeted delivery of drugs and nucleic acids for the treatment of lung cancer. In a similar study, we used a complex liposomal drug delivery system containing anticancer drug doxorubicin and both MRP1 and BCL2 targeting antisense oligonucleotides for inhalation treatment in lung cancer cells.
   abstract: Systemic delivery of therapeutics for treatment of lung diseases has several limitations including poor organ distribution of delivered payload with relatively low accumulation of active substances in the lungs and severe adverse side effects. In contrast, nanocarrier based therapeutics provide a broad range of opportunities due to their ability to encapsulate substances with different aqueous solubility, transport distinct types of cargo, target therapeutics specifically to the deceased organ, cell, or cellular organelle limiting adverse side effects and increasing the efficacy of therapy. Moreover, many nanotherapeutics can be delivered by inhalation locally to the lungs avoiding systemic circulation. In addition, nanoscale based delivery systems can be multifunctional, simultaneously carrying out several tasks including diagnostics, treatment and suppression of cellular resistance to the treatment. Nanoscale delivery systems improve the clinical efficacy of conventional therapeutics allowing new approaches for the treatment of respiratory diseases which are difficult to treat or possess intrinsic or acquired resistance to treatment. The present review summarizes recent advances in the development of nanocarrier based therapeutics for local and targeted delivery of drugs, nucleic acids and imaging agents for diagnostics and treatment of various diseases such as cancer, cystic fibrosis, and coronavirus.
        url: https://www.ncbi.nlm.nih.gov/pubmed/33173809/
        doi: 10.1002/adtp.202000203

         id: cord-130351-w9mij6c6
     author: Mamidala, Estari
      title: In silico identification of clinically approved medicines against the main protease of SARS-CoV-2, causative agent of covid-19
       date: 2020-04-25
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: The COVID-19 pandemic triggered by SARS-CoV-2 is a worldwide health disaster. Main protease is an attractive drug target among coronaviruses, due to its vital role in processing the polyproteins that are translated from the viral RNA. There is presently no exact drug or treatment for this diseases caused by SARS-CoV-2. In the present study, we report the potential inhibitory activity of some FDA approved drugs against SARS-CoV-2 main protease by molecular docking study to investigate their binding affinity in protease active site. Docking studies revealed that drug Oseltamivir (anti-H1N1 drug), Rifampin (anti-TB drug), Maraviroc, Etravirine, Indinavir, Rilpivirine (anti-HIV drugs) and Atovaquone, Quinidine, Halofantrine, Amodiaquine, Tetracylcine, Azithromycin, hydroxycholoroquine (anti-malarial drugs) among others binds in the active site of the protease with similar or higher affinity. However, the in-silico abilities of the drug molecules tested in this study, further needs to be validated by carrying out in vitro and in vivo studies. Moreover, this study spreads the potential use of current drugs to be considered and used to comprise the fast expanding SARS-CoV-2 infection.
        url: https://arxiv.org/pdf/2004.12055v1.pdf
        doi: nan

         id: cord-276886-vcmkz8lh
     author: Mandsberg, Nikolaj Kofoed
      title: Orally ingestible medical devices for gut engineering
       date: 2020-05-13
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Orally ingestible medical devices provide significant advancement for diagnosis and treatment of gastrointestinal (GI) tract-related conditions. From micro- to macroscale devices, with designs ranging from very simple to complex, these medical devices can be used for site-directed drug delivery in the GI tract, real-time imaging and sensing of gut biomarkers. Equipped with uni-direction release, or self-propulsion, or origami design, these microdevices are breaking the barriers associated with drug delivery, including biologics, across the GI tract. Further, on-board microelectronics allow imaging and sensing of gut tissue and biomarkers, providing a more comprehensive understanding of underlying pathophysiological conditions. We provide an overview of recent advances in orally ingestible medical devices towards drug delivery, imaging and sensing. Challenges associated with gut microenvironment, together with various activation/actuation modalities of medical devices for micromanipulation of the gut are discussed. We have critically examined the relationship between materials–device design–pharmacological responses with respect to existing regulatory guidelines and provided a clear roadmap for the future.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32416112/
        doi: 10.1016/j.addr.2020.05.004

         id: cord-337738-2qck1j1w
     author: Martin, Jennifer H.
      title: Buying time: Drug repurposing to treat the host in COVID‐19H
       date: 2020-06-23
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: In 2016 Fedson stated …. “For almost two decades, leading scientists and health officials have warned that we must prepare for a potentially devastating global pandemic of an infectious disease. Initial concern was focused on …H5N1…. More recently…a devastating outbreak of Ebola virus..(and) several other emerging viruses are believed to seriously threaten global health and global security. To prepare, scientists have been urged to discover new vaccines and treatments for these emerging viruses. At the same time, political leaders have been urged by global health experts to invest millions in a “top down” restructuring of the global health system. This article takes a different view. It focuses on an alternative approach to the scientific discovery of treatments for individual patients, reviews the mechanisms of action and clinical experience with specific drugs that might be useful, and considers whether or not recent lessons regarding this “bottom up” approach to treatment have been learned”. Now with a new virus and pandemic upon us, Fedson's 2016 comments appear chilling, are cause for reflection on what we have learnt and importantly offer focus on an immediate opportunity in the area of treating the host (Fedson DS, Ann Transl Med, 2016;4:421).
        url: https://www.ncbi.nlm.nih.gov/pubmed/32578336/
        doi: 10.1002/prp2.620

         id: cord-334170-85x5vmyi
     author: Masoudi-Sobhanzadeh, Yosef
      title: Synthetic repurposing of drugs against hypertension: a datamining method based on association rules and a novel discrete algorithm
       date: 2020-07-16
      words: 6507.0
  sentences: 383.0
      pages: 
     flesch: 56.0
      cache: ./cache/cord-334170-85x5vmyi.txt
        txt: ./txt/cord-334170-85x5vmyi.txt
    summary: title: Synthetic repurposing of drugs against hypertension: a datamining method based on association rules and a novel discrete algorithm RESULTS: A novel two-step data mining method, which is based on the If-Then association rules as well as a novel discrete optimization algorithm, was introduced and applied to the synthetic repurposing of drugs for HT. CONCLUSION: Since the proposed synthetic method uses medications in small dosages, it might revive some failed drug development projects and put forward a suitable plan for treating different diseases such as COVID-19 and HT. Based on the obtained results, it can be concluded that Trader (the newly introduced algorithm) is more efficient than the other state-of-the-art algorithms and proposes some better synthetic drug lists to treat HT. To discover the hidden applications of the existing drugs, a drug repositioning method, which is based on the newly introduced discrete optimization algorithm (Trader) and If-Then association rules, was proposed.
   abstract: BACKGROUND: Drug repurposing aims to detect the new therapeutic benefits of the existing drugs and reduce the spent time and cost of the drug development projects. The synthetic repurposing of drugs may prove to be more useful than the single repurposing in terms of reducing toxicity and enhancing efficacy. However, the researchers have not given it serious consideration. To address the issue, a novel datamining method is introduced and applied to repositioning of drugs for hypertension (HT) which is a serious medical condition and needs some improved treatment plans to help treat it. RESULTS: A novel two-step data mining method, which is based on the If-Then association rules as well as a novel discrete optimization algorithm, was introduced and applied to the synthetic repurposing of drugs for HT. The required data were also extracted from DrugBank, KEGG, and DrugR+ databases. The findings indicated that based on the different statistical criteria, the proposed method outperformed the other state-of-the-art approaches. In contrast to the previously proposed methods which had failed to discover a list on some datasets, our method could find a combination list for all of them. CONCLUSION: Since the proposed synthetic method uses medications in small dosages, it might revive some failed drug development projects and put forward a suitable plan for treating different diseases such as COVID-19 and HT. It is also worth noting that applying efficient computational methods helps to produce better results.
        url: https://doi.org/10.1186/s12859-020-03644-w
        doi: 10.1186/s12859-020-03644-w

         id: cord-034406-i1hbx3pz
     author: Matthews, Abigail A.
      title: Developing inhaled protein therapeutics for lung diseases
       date: 2020-10-30
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Biologic therapeutics such as protein/polypeptide drugs are conventionally administered systemically via intravenous injection for the treatment of diseases including lung diseases, although this approach leads to low target site accumulation and the potential risk for systemic side effects. In comparison, topical delivery of protein drugs to the lung via inhalation is deemed to be a more effective approach for lung diseases, as proteins would directly reach the target in the lung while exhibiting poor diffusion into the systemic circulation, leading to higher lung drug retention and efficacy while minimising toxicity to other organs. This review examines the important considerations and challenges in designing an inhaled protein therapeutics for local lung delivery: the choice of inhalation device, structural changes affecting drug deposition in diseased lungs, clearance mechanisms affecting an inhaled protein drug’s lung accumulation, protein stability, and immunogenicity. Possible approaches to overcoming these issues will also be discussed.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595758/
        doi: 10.1186/s43556-020-00014-z

         id: cord-309025-jo0rqy3y
     author: Maurya, Priyanka
      title: Inhalable hybrid nanocarriers for respiratory disorders
       date: 2020-09-18
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Rapid advancements in the field of drug delivery lead to increased use of inhalable formulations as they are cost effective, noninvasive, and targeted and have less systemic side effects and above all better patient compliance. Development of inhalable hybrid systems has offered manifold advantages to this area of drug delivery. Inclusion of polymer and lipid, inorganic and organic substances, and metallic nanoparticles all of them aim to achieve codelivery of drugs which are incompatible in single phase systems. The recent progress in nanotechnology has gained momentum toward delivery of siRNA and miRNA and vaccines to the targeted site. The present work is an attempt to compile all the hybrid and inhalable systems to give readers an overview toward this delivery system as much more work is needed in this field to achieve better resolution of inflammatory disorders.
        url: https://www.sciencedirect.com/science/article/pii/B9780128206584000133
        doi: 10.1016/b978-0-12-820658-4.00013-3

         id: cord-253115-ekgdsv4f
     author: Mehta, Meenu
      title: Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases
       date: 2019-08-01
      words: 7317.0
  sentences: 457.0
      pages: 
     flesch: 39.0
      cache: ./cache/cord-253115-ekgdsv4f.txt
        txt: ./txt/cord-253115-ekgdsv4f.txt
    summary: Commonly used drug delivery systems for respiratory diseases are polymer-based, lipid-based and peptide-based, and among these three, the lipid-based carriers are the most commonly used vectors for delivering RNAi. They include solid lipid nanoparticles, cationic liposomes, lipidoids, solid nanostructured lipid carriers and pH-responsive lipids [26] . The effective delivery of the drug and siRNA induced cell death of lung tumor cells by targeted gene silencing [56] . Glud et al., investigated pulmonary gene silencing effect of small interfering locked nucleic acid (siLNAs), targeting enhanced-greenfluorescent-protein (EGFP) in lung bronchoepithelium upon intravenous delivery of naked siLNAs and intranasal delivery of naked siLNA or chitosan based siLNA mucoadhesive nanoparticles. This study demonstrated that SAMiRNA nanoparticle is a stable siRNA silencing platform with less toxicity for effective in vivo targeting of genes involved in the pathogenesis of respiratory diseases [96] . Overcoming cisplatin resistance in non-small cell lung cancer with Mad2 silencing siRNA delivered systemically using EGFR-targeted chitosan nanoparticles
   abstract: Abstract Oligonucleotide-based therapies are advanced novel interventions used in the management of various respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). These agents primarily act by gene silencing or RNA interference. Better methodologies and techniques are the need of the hour that can deliver these agents to tissues and cells in a target specific manner by which their maximum potential can be reached in the management of chronic inflammatory diseases. Nanoparticles play an important role in the target-specific delivery of drugs. In addition, oligonucleotides also are extensively used for gene transfer in the form of polymeric, liposomal and inorganic carrier materials. Therefore, the current review focuses on various novel dosage forms like nanoparticles, liposomes that can be used efficiently for the delivery of various oligonucleotides such as siRNA and miRNA. We also discuss the future perspectives and targets for oligonucleotides in the management of respiratory diseases.
        url: https://www.ncbi.nlm.nih.gov/pubmed/31136735/
        doi: 10.1016/j.cbi.2019.05.028

         id: cord-275828-c6d6nk7x
     author: Mikasa, Keiichi
      title: JAID/JSC Guidelines for the Treatment of Respiratory Infectious Diseases: The Japanese Association for Infectious Diseases/Japanese Society of Chemotherapy – The JAID/JSC Guide to Clinical Management of Infectious Disease/Guideline-preparing Committee Respiratory Infectious Disease WG
       date: 2016-07-31
      words: 39672.0
  sentences: 2522.0
      pages: 
     flesch: 42.0
      cache: ./cache/cord-275828-c6d6nk7x.txt
        txt: ./txt/cord-275828-c6d6nk7x.txt
    summary: -SBT/ABPC, intravenous drip, 3 g/3e4 times a day -CTRX, intravenous drip, 1 g/twice a day or 2 g/once a day -CTX, intravenous drip, 1e2 g/2e3 times a day -LVFX, intravenous drip, 500 mg/once a day (2) Cases of late-onset hospital-acquired pneumonia or ventilator-associated pneumonia in which the risk of resistant bacteria is high An antimicrobial drug with anti-pseudomonal activity that targets non-glucose-fermentative gram-negative rod should be administered [50, 51, 68] -To treat polymicrobial infection, the administration of an antimicrobial drug with an activity against obligate anaerobe is not always necessary [67, 70] . -SBT/ABPC, intravenous drip, 3 g/3e4 times a day -CTRX, intravenous drip, 2 g/once a day or 1 g/twice a day -CTX, intravenous drip, 1e2 g/2e3 times a day -LVFX, intravenous drip, 500 mg/once a day (2) Late-onset hospital-acquired pneumonia or cases in which there is a risk of multi-drug-resistant bacteria In addition to the above pathogens, the involvement of non-glucose-fermentative gram negative bacteria or ESBLproducing enteric bacteria must be considered. For the treatment of immunodeficiency-/blood disease-related pneumonia in children, antimicrobial drug therapy should also be basically selected, considering causative microorganisms.
   abstract: nan
        url: https://api.elsevier.com/content/article/pii/S1341321X16000283
        doi: 10.1016/j.jiac.2015.12.019

         id: cord-258128-qtmjgrml
     author: Mirjalili, Mahtabalsadat
      title: Coronavirus Disease 2019 (COVID-19) and Transplantation: Pharmacotherapeutic Management of Immunosuppression Regimen
       date: 2020-07-03
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: The 2019 novel coronavirus disease (COVID-19) was first detected in Wuhan, Hubei Province, China, in late 2019. Since then, COVID-19 has spread to more than 200 countries in the world, and a global pandemic has been declared by the World Health Organization (WHO). At present, no vaccines or therapeutic regimens with proven efficacy are available for the management of COVID-19. Hydroxychloroquine/chloroquine, lopinavir/ritonavir, ribavirin, interferons, umifenovir, remdesivir, and interleukin antagonists, such as tocilizumab, have been recommended as potential treatment options in COVID-19. Transplant patients receiving immunosuppressant medications are at the highest risk of severe illness from COVID-19. At the same time, with regard to receiving polypharmacy and immunosuppressants, treatment options should be chosen with more attention in this population. Considering drug–drug interactions and adverse effects of medications used for the treatment of COVID-19, such as QT prolongation, the dose reduction of some immunosuppressants or avoidance is recommended in transplant recipients with COVID-19. Thus, this narrative review describes clinically important considerations about the treatment of COVID-19 and immunosuppressive regimens regarding modifications, side effects, and interactions in adult kidney or liver allograft recipients.
        url: https://doi.org/10.2147/tcrm.s256246
        doi: 10.2147/tcrm.s256246

         id: cord-214795-8jweuq50
     author: Mongia, Aanchal
      title: DeepVir -- Graphical Deep Matrix Factorization for"In Silico"Antiviral Repositioning: Application to COVID-19
       date: 2020-09-22
      words: 6420.0
  sentences: 369.0
      pages: 
     flesch: 47.0
      cache: ./cache/cord-214795-8jweuq50.txt
        txt: ./txt/cord-214795-8jweuq50.txt
    summary: Results on our curated RNA drug virus association (DVA) dataset shows that the proposed approach excels over state-of-the-art graph regularized matrix completion techniques. It shows how the matrix completion framework can be used to computationally predict the drugs that could be effective against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus responsible for the ongoing pandemic, COVID-19 (COrona VIrus Disease-2019). In this present work, we propose to solve the problem of drug-virus association prediction via graph regularized deep matrix factorization. Among all the methodologies compared in [52] , graph regularized matrix factorization based technique (GRMF) provided the best results for the validation setting where drugs are predicted for novel viruses. In our proposed technique, multi-graph regularization is incorporated in the deep matrix factorization formulation with the aim to incorporate the metadata associated with the drugs and viruses in the form of similarity information as shown below:
   abstract: This work formulates antiviral repositioning as a matrix completion problem where the antiviral drugs are along the rows and the viruses along the columns. The input matrix is partially filled, with ones in positions where the antiviral has been known to be effective against a virus. The curated metadata for antivirals (chemical structure and pathways) and viruses (genomic structure and symptoms) is encoded into our matrix completion framework as graph Laplacian regularization. We then frame the resulting multiple graph regularized matrix completion problem as deep matrix factorization. This is solved by using a novel optimization method called HyPALM (Hybrid Proximal Alternating Linearized Minimization). Results on our curated RNA drug virus association (DVA) dataset shows that the proposed approach excels over state-of-the-art graph regularized matrix completion techniques. When applied to"in silico"prediction of antivirals for COVID-19, our approach returns antivirals that are either used for treating patients or are under for trials for the same.
        url: https://arxiv.org/pdf/2009.10333v1.pdf
        doi: nan

         id: cord-232446-vvb2ffhv
     author: Mongia, Aanchal
      title: A computational approach to aid clinicians in selecting anti-viral drugs for COVID-19 trials
       date: 2020-07-03
      words: 7123.0
  sentences: 382.0
      pages: 
     flesch: 47.0
      cache: ./cache/cord-232446-vvb2ffhv.txt
        txt: ./txt/cord-232446-vvb2ffhv.txt
    summary: In view to assist acceleration of this process (by pruning down the search space), we create and share a publicly available DVA database, along with a number of matrix completion techniques (mentioned above) for drug-virus association prediction. Such a computational approach requires the chemical structure of the drugs and, in case of graph-regularized matrix completion techniques, the genome of the viruses, or existing associations otherwise. A clear observation from the experiments is that the graph regularized-based matrix completion algorithms that incorporate the similarity information associated with the drugs and viruses, perform fairly well giving an AUC greater or equal than 0.83 in CV1. It can be noted that the standard matrix completion methods, which do not take into account the metadata, fail to learn from the association data giving a near-random performance as far as the prediction on novel viruses is concerned, depicting how very important the similarity information is.
   abstract: COVID-19 has fast-paced drug re-positioning for its treatment. This work builds computational models for the same. The aim is to assist clinicians with a tool for selecting prospective antiviral treatments. Since the virus is known to mutate fast, the tool is likely to help clinicians in selecting the right set of antivirals for the mutated isolate. The main contribution of this work is a manually curated database publicly shared, comprising of existing associations between viruses and their corresponding antivirals. The database gathers similarity information using the chemical structure of drugs and the genomic structure of viruses. Along with this database, we make available a set of state-of-the-art computational drug re-positioning tools based on matrix completion. The tools are first analysed on a standard set of experimental protocols for drug target interactions. The best performing ones are applied for the task of re-positioning antivirals for COVID-19. These tools select six drugs out of which four are currently under various stages of trial, namely Remdesivir (as a cure), Ribavarin (in combination with others for cure), Umifenovir (as a prophylactic and cure) and Sofosbuvir (as a cure). Another unanimous prediction is Tenofovir alafenamide, which is a novel tenofovir prodrug developed in order to improve renal safety when compared to the counterpart tenofovir disoproxil. Both are under trail, the former as a cure and the latter as a prophylactic. These results establish that the computational methods are in sync with the state-of-practice. We also demonstrate how the selected drugs change as the SARS-Cov-2 mutates over time, suggesting the importance of such a tool in drug prediction. The dataset and software is available publicly at https://github.com/aanchalMongia/DVA and the prediction tool with a user-friendly interface is available at http://dva.salsa.iiitd.edu.in.
        url: https://arxiv.org/pdf/2007.01902v2.pdf
        doi: nan

         id: cord-268088-y4vg7frb
     author: Montané, Xavier
      title: Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy
       date: 2020-07-23
      words: 11101.0
  sentences: 581.0
      pages: 
     flesch: 42.0
      cache: ./cache/cord-268088-y4vg7frb.txt
        txt: ./txt/cord-268088-y4vg7frb.txt
    summary: Among the natural compounds that produce beneficial effects on human health, polyphenols have shown potential therapeutic applications in cancer due to their protective functions in plants, their use as food additives, and their excellent antioxidant properties. This review shows a wide range of trials in which polyphenolic compounds play a crucial role as anticancer medicines alone or in combination with other drugs at different stages of cancer: cancer initiation, promotion, and growth or progression. In point of fact, studies demonstrated that resveratrol has in vitro effects against a large range of human tumors: breast, skin, ovary, stomach, prostate, colon, liver, pancreas, cervix, thyroid carcinoma cells, lymphoid, and myeloid cancer cells [22] . In point of fact, studies demonstrated that resveratrol has in vitro effects against a large range of human tumors: breast, skin, ovary, stomach, prostate, colon, liver, pancreas, cervix, thyroid carcinoma cells, lymphoid, and myeloid cancer cells [22] .
   abstract: The development of anticancer therapies that involve natural drugs has undergone exponential growth in recent years. Among the natural compounds that produce beneficial effects on human health, polyphenols have shown potential therapeutic applications in cancer due to their protective functions in plants, their use as food additives, and their excellent antioxidant properties. The possibility of combining conventional drugs—which are usually more aggressive than natural compounds—with polyphenols offers very valuable advantages such as the building of more efficient anticancer therapies with less side effects on human health. This review shows a wide range of trials in which polyphenolic compounds play a crucial role as anticancer medicines alone or in combination with other drugs at different stages of cancer: cancer initiation, promotion, and growth or progression. Moreover, the future directions in applications of various polyphenols in cancer therapy are emphasized.
        url: https://doi.org/10.3390/molecules25153342
        doi: 10.3390/molecules25153342

         id: cord-348245-pf5mlzrw
     author: Moura-Neto, José A.
      title: Position statement from the Brazilian Society of Nephrology regarding chloroquine and hydroxychloroquine drug dose adjustment according to renal function
       date: 2020-08-26
      words: 962.0
  sentences: 57.0
      pages: 
     flesch: 47.0
      cache: ./cache/cord-348245-pf5mlzrw.txt
        txt: ./txt/cord-348245-pf5mlzrw.txt
    summary: On the first day of April 2020, Informative Note nº 6/2020-DAF/SCTIE/MS was published, establishing that the Brazilian Ministry of Health (MS) would make the medications available for use, in confirmed cases and at medical criteria, chloroquine and hydroxychloroquine as adjunctive therapy in the treatment of severe forms in hospitalized patients, without other supportive measures being neglected in their favor 1 . On April 6, the MS published "Guidelines for the diagnosis and treatment of Covid-19", in which it also instructed on the use of chloroquine and hydroxychloroquine as adjuvant therapy in severe forms of the disease, in confirmed cases and upon medical discretion 2 . Given the above and the associated risks, the Brazilian Society of Nephrology advises its associate doctors to prescribe one of these drugs according to the recommendations established by CFM and MS, which recommend a 50% reduction in the recommended dose of chloroquine and hydroxychloroquine in patients with glomerular filtration rate <10 mL/min/1.72 m 2 , in dialysis or conservative treatment.
   abstract: Chloroquine and hydroxychloroquine have shown promising preliminary results and have been discussed as therapeutic options for patients with Covid-19. Despite the lack of robust evidence demonstrating the benefits and justifying the use of one of these drugs, the final decision is the responsibility of the attending physician and should be individualized and shared, whenever possible. This position statement recommends dosage adjustment for these drugs in the context of renal impairment.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32877501/
        doi: 10.1590/2175-8239-jbn-2020-s113

         id: cord-317993-012hx4kc
     author: Movia, Dania
      title: Preclinical Development of Orally Inhaled Drugs (OIDs)—Are Animal Models Predictive or Shall We Move Towards In Vitro Non-Animal Models?
       date: 2020-07-24
      words: 6885.0
  sentences: 369.0
      pages: 
     flesch: 42.0
      cache: ./cache/cord-317993-012hx4kc.txt
        txt: ./txt/cord-317993-012hx4kc.txt
    summary: SIMPLE SUMMARY: This commentary focuses on the methods currently available to test the efficacy and safety of new orally inhaled drugs for the treatment of uncurable respiratory diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis or lung cancer, prior to entering human experimentation. Inhalation is the preferred administration method for treating respiratory diseases [13] , as: (i) it delivers the drug directly at the site of action, resulting in a rapid therapeutic onset with considerably lower drug doses, (ii) it is painless and minimally invasive thus improving patients'' compliance, and (iii) it avoids first-pass metabolism, providing optimal pharmacokinetic conditions for drug absorption and reducing systemic side effects [14] [15] [16] . In the context of OID preclinical testing, lung organoids can be used for modeling respiratory diseases and, therefore, as a platform for screening the efficacy of inhalation therapies [115, 116] .
   abstract: SIMPLE SUMMARY: This commentary focuses on the methods currently available to test the efficacy and safety of new orally inhaled drugs for the treatment of uncurable respiratory diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis or lung cancer, prior to entering human experimentation. The key question that the authors try to address in this manuscript is whether there is value in using and refining current animal models for this pre-clinical testing, or whether these should be relinquished in favor of new, more human-relevant non-animal methods. ABSTRACT: Respiratory diseases constitute a huge burden in our society, and the global respiratory drug market currently grows at an annual rate between 4% and 6%. Inhalation is the preferred administration method for treating respiratory diseases, as it: (i) delivers the drug directly at the site of action, resulting in a rapid onset; (ii) is painless, thus improving patients’ compliance; and (iii) avoids first-pass metabolism reducing systemic side effects. Inhalation occurs through the mouth, with the drug generally exerting its therapeutic action in the lungs. In the most recent years, orally inhaled drugs (OIDs) have found application also in the treatment of systemic diseases. OIDs development, however, currently suffers of an overall attrition rate of around 70%, meaning that seven out of 10 new drug candidates fail to reach the clinic. Our commentary focuses on the reasons behind the poor OIDs translation into clinical products for the treatment of respiratory and systemic diseases, with particular emphasis on the parameters affecting the predictive value of animal preclinical tests. We then review the current advances in overcoming the limitation of animal animal-based studies through the development and adoption of in vitro, cell-based new approach methodologies (NAMs).
        url: https://doi.org/10.3390/ani10081259
        doi: 10.3390/ani10081259

         id: cord-315918-12rbbe8c
     author: Mukherjee, Pulok K.
      title: Antiviral Evaluation of Herbal Drugs
       date: 2019-06-21
      words: 12776.0
  sentences: 660.0
      pages: 
     flesch: 49.0
      cache: ./cache/cord-315918-12rbbe8c.txt
        txt: ./txt/cord-315918-12rbbe8c.txt
    summary: To test the inhibitory activity of a new antiviral agent, it is first necessary to select the host cell system(s) in which the virus replication can be measured. (d) Assay systems based on the measurement of specialized functions and viral products; a number of viruses do not produce plaques nor do they cause CPE readily, but they may be quantified by certain specialized functions based on their unique properties, for example, hemagglutination and hemadsorption tests used to study the antiviral activity against myxoviruses and ELISA, used to determine the extent of virus replication and, thus, obtain a measure of the inhibitory effect of various antiviral agents on virus replication, etc. On the other hand, the antiviral activity is determined by comparing the virus titers of infected cells, which have been cultured with a maintenance medium containing plant extracts or test substances and a maintenance medium without test material (Colegate and Molyneux, 1993) .
   abstract: The viral infection and resistance to the existing antiviral drugs are alarming, which is a serious public health concern. Medicinal plants are valuable resources for treatment of viral infections and can be used for the management of infections like herpes simplex virus (HSV), human immunodeficiency virus (HIV), influenza, etc. The antiviral screening of plant extracts should be highly selective, specific, and sensitive for bioactivity guided isolation of the active compounds from the plant extracts. The antiviral screening system should be validated for accuracy, reproducibility, simplicity, and cost effectiveness. This chapter highlights on various aspects for screening and evaluation of antiviral natural components including factors affecting antiviral in vivo studies, host cells, organisms, and culture media followed by different virus-specific assays for antiviral screening of natural products.
        url: https://api.elsevier.com/content/article/pii/B9780128133743000168
        doi: 10.1016/b978-0-12-813374-3.00016-8

         id: cord-020766-0gacqii4
     author: Murthy, Sreekant
      title: Nanotechnology: Towards the detection and treatment of inflammatory diseases
       date: 2006
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Biological systems operate at the nanoscale. Nanomedicine is the application of nanotechnology to monitor and treat biological systems in health and disease. This is accomplished by real time monitoring of molecular signaling at the cellular and tissue level. During the past decade, there has been an explosion in this field, resulting in revolutionary advances in determining the microstructure and function of living systems. These discoveries have led to the development of powerful tools for fundamental biological and medical research. Nanotechnology has been applied to targeted drug delivery to minimize side effects, creating implantable materials as scaffolds for tissue engineering, creating implantable devices, surgical aids and nanorobotics, as well as throughput drug screening and medical diagnostic imaging. The nanoinitiatives are funded by governments and private sources throughout the world to develop or further refine the technology to provide the beyond-imaginable, most sophisticated tools to a physician and scientists to inflammatory diseases. No doubt, there will be many technical, regulatory and legal challenges in the deployment of these technologies. Unquestionably, there is enough desire and commitment to meet these challenges for the good of society and betterment of the quality of life.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147450/
        doi: 10.1007/978-3-7643-7520-1_8

         id: cord-287758-da11ypiy
     author: Mônica Vitalino de Almeida, Sinara
      title: COVID-19 therapy: what weapons do we bring into battle?
       date: 2020-09-10
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Urgent treatments, in any modality, to fight SARS-CoV-2 infections are desired by society in general, by health professionals, by Estate-leaders and, mainly, by the scientific community, because one thing is certain amidst the numerous uncertainties regarding COVID-19: knowledge is the means to discover or to produce an effective treatment against this global disease. Scientists from several areas in the world are still committed to this mission, as shown by the accelerated scientific production in the first half of 2020 with over 25,000 published articles related to the new coronavirus. Three great lines of publications related to COVID-19 were identified for building this article: The first refers to knowledge production concerning the virus and pathophysiology of COVID-19; the second regards efforts to produce vaccines against SARS-CoV-2 at a speed without precedent in the history of science; the third comprehends the attempts to find a marketed drug that can be used to treat COVID-19 by drug repurposing. In this review, the drugs that have been repurposed so far are grouped according to their chemical class. Their structures will be presented to provide better understanding of their structural similarities and possible correlations with mechanisms of actions. This can help identifying anti-SARS-CoV-2 promising therapeutic agents.
        url: https://doi.org/10.1016/j.bmc.2020.115757
        doi: 10.1016/j.bmc.2020.115757

         id: cord-263074-qxiynbl2
     author: Nabi, Bushra
      title: Nano-based anti-tubercular drug delivery: an emerging paradigm for improved therapeutic intervention
       date: 2020-05-16
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Tuberculosis (TB) classified as one of the most fatal contagious diseases is of prime concern globally. Mycobacterium tuberculosis is the causative agent that ingresses within the host cells. The approved conventional regimen, though the only viable option available, is unfavorably impacting the quality of life of the affected individual. Despite newer antibiotics gaining light, there is an unending demand for more therapeutic alternatives. Therefore, substantial continuous endeavors are been undertaken to come up with novel strategies to curb the disease, the stepping stone being nanotechnology. This approach is instrumental in overcoming the anomalies associated with conventional therapy owing to their intriguing attributes and leads to optimization of the therapeutic effect to a certain extent. This review focusses on the different types of nanocarrier systems that are being currently explored by the researchers for the delivery of anti-tubercular drugs, the outcomes achieved by them, and their prospects. [Figure: see text]
        url: https://www.ncbi.nlm.nih.gov/pubmed/32418158/
        doi: 10.1007/s13346-020-00786-5

         id: cord-256852-lrz17bdx
     author: Nayyar, Gaurvika M. L.
      title: Responding to the Pandemic of Falsified Medicines
       date: 2015-06-03
      words: 4208.0
  sentences: 201.0
      pages: 
     flesch: 39.0
      cache: ./cache/cord-256852-lrz17bdx.txt
        txt: ./txt/cord-256852-lrz17bdx.txt
    summary: 15 The U.S. Institute of Medicine (IOM) has published a report "Countering the Problem of Falsified and Substandard Drugs." 16 The IOM recommendations to "stem the global trade" in such products are laudable in advising that the U.S. Food and Drug Administration (FDA), the National Institute of Standards and Technology, and other U.S. and international pharmaceutical and financing agencies be more actively involved in setting standards and financing improvements; yet this report falls far short of making a strong call for standardized, agreed-upon quality assessment technologies; an international law convention; and a more activist, internationally recognized lead organization, all three of which are essential for stopping the many health threats of fake drugs.
   abstract: Over the past decade, the number of countries reporting falsified (fake, spurious/falsely labeled/counterfeit) medicines and the types and quantities of fraudulent drugs being distributed have increased greatly. The obstacles in combating falsified pharmaceuticals include 1) lack of consensus on definitions, 2) paucity of reliable and scalable technology to detect fakes before they reach patients, 3) poor global and national leadership and accountability systems for combating this scourge, and 4) deficient manufacturing and regulatory challenges, especially in China and India where fake products often originate. The major needs to improve the quality of the world's medicines fall into three main areas: 1) research to develop and compare accurate and affordable tools to identify high-quality drugs at all levels of distribution; 2) an international convention and national legislation to facilitate production and utilization of high-quality drugs and protect all countries from the criminal and the negligent who make, distribute, and sell life-threatening products; and 3) a highly qualified, well-supported international science and public health organization that will establish standards, drug-quality surveillance, and training programs like the U.S. Food and Drug Administration. Such leadership would give authoritative guidance for countries in cooperation with national medical regulatory agencies, pharmaceutical companies, and international agencies, all of which have an urgent interest and investment in ensuring that patients throughout the world have access to good quality medicines. The organization would also advocate strongly for including targets for achieving good quality medicines in the United Nations Millennium Development Goals and Sustainable Development Goals.
        url: https://doi.org/10.4269/ajtmh.14-0393
        doi: 10.4269/ajtmh.14-0393

         id: cord-264779-71s7e18i
     author: Neumann, Natalie R.
      title: Medical Toxicology and COVID-19: Our Role in a Pandemic
       date: 2020-04-30
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pubmed/32356251/
        doi: 10.1007/s13181-020-00778-4

         id: cord-102823-zult69f2
     author: Nguyen, Thin
      title: GraphDTA: Predicting drug–target binding affinity with graph neural networks
       date: 2020-10-02
      words: 4962.0
  sentences: 283.0
      pages: 
     flesch: 56.0
      cache: ./cache/cord-102823-zult69f2.txt
        txt: ./txt/cord-102823-zult69f2.txt
    summary: We propose a new model called GraphDTA that represents drugs as graphs and uses graph neural networks to predict drug--target affinity. We show that graph neural networks not only predict drug--target affinity better than non-deep learning models, but also outperform competing deep learning methods. Our results confirm that deep learning models are appropriate for drug--target binding affinity prediction, and that representing drugs as graphs can lead to further improvements. In this article, we propose GraphDTA, a new neural network architecture capable of directly modelling drugs as molecular graphs, and show that this approach outperforms state-of-the-art deep learning models on two drug-target affinity prediction benchmarks. Although we focus on drug-target affinity prediction, our GraphDTA model is a generic solution for any similar problem where either data input can be represented as a graph.
   abstract: The development of new drugs is costly, time consuming, and often accompanied with safety issues. Drug repurposing can avoid the expensive and lengthy process of drug development by finding new uses for already approved drugs. In order to repurpose drugs effectively, it is useful to know which proteins are targeted by which drugs. Computational models that estimate the interaction strength of new drug--target pairs have the potential to expedite drug repurposing. Several models have been proposed for this task. However, these models represent the drugs as strings, which is not a natural way to represent molecules. We propose a new model called GraphDTA that represents drugs as graphs and uses graph neural networks to predict drug--target affinity. We show that graph neural networks not only predict drug--target affinity better than non-deep learning models, but also outperform competing deep learning methods. Our results confirm that deep learning models are appropriate for drug--target binding affinity prediction, and that representing drugs as graphs can lead to further improvements. Availability of data and materials The proposed models are implemented in Python. Related data, pre-trained models, and source code are publicly available at https://github.com/thinng/GraphDTA. All scripts and data needed to reproduce the post-hoc statistical analysis are available from https://doi.org/10.5281/zenodo.3603523. Contact Thin.Nguyen@deakin.edu.au
        url: https://doi.org/10.1101/684662
        doi: 10.1101/684662

         id: cord-299400-j18pj11d
     author: Norinder, Ulf
      title: Existing highly accumulating lysosomotropic drugs with potential for repurposing to target COVID-19
       date: 2020-07-30
      words: 5310.0
  sentences: 251.0
      pages: 
     flesch: 42.0
      cache: ./cache/cord-299400-j18pj11d.txt
        txt: ./txt/cord-299400-j18pj11d.txt
    summary: We propose that the antiviral activity of (hydroxy)chloroquine and azithromycin is shared among all strong lysosomotropic drugs and is a consequence of their extremely high accumulation in cells and membranes, and subsequently of all the processes affected by this pharmacokinetic property. Among listed drugs with antiviral effects, the CADs include: psychoactive drugs (chlorpromazine, fluoxetine, clomipramine); antiarrhythmics (amiodarone); antimalarials (chloroquine, hydroxychloroquine, amodiaquine, mefloquine, quinacrine); channel blockers (amiodarone, verapamil, manidipine); antibacterial (azithromycin); estrogen receptor modulators (tamoxifen, raloxifene, toremifene); two antivirals, the only ones known to utilize CADs mechanism of J o u r n a l P r e -p r o o f antiviral action via the inhibition of endosomal pathway (arbidol (umifenovir) and tilorone (with additional activity of interferon induction)) (Boriskin et al., 2008 , Ekins et al., 2018 .
   abstract: Given the speed of viral infection spread, repurposing of existing drugs has been given the highest priority in combating the ongoing COVID-19 pandemic. Only drugs that are already registered or close to registration, and therefore have passed lengthy safety assessments, have a chance to be tested in clinical trials and reach patients quickly enough to help in the current disease outbreak. Here, we have reviewed available evidence and possible ways forward to identify already existing pharmaceuticals displaying modest broad-spectrum antiviral activity which is likely linked to their high accumulation in cells. Several well studied examples indicate that these drugs accumulate in lysosomes, endosomes and biological membranes in general, and thereby interfere with endosomal pathway and intracellular membrane trafficking crucial for viral infection. With the aim to identify other lysosomotropic drugs with possible inherent antiviral activity, we have applied a set of clear physicochemical, pharmacokinetic and molecular criteria on 530 existing drugs. In addition to publicly available data, we have also used our in silico model for the prediction of accumulation in lysosomes and endosomes. By this approach we have identified 36 compounds with possible antiviral effects, also against coronaviruses. For 14 of them evidence of broad-spectrum antiviral activity has already been reported, adding support to the value of this approach. Presented pros and cons, knowledge gaps and methods to identify lysosomotropic antivirals, can help in the evaluation of many drugs currently in clinical trials considered for repurposing to target COVID-19, as well as open doors to finding more potent and safer alternatives.
        url: https://doi.org/10.1016/j.biopha.2020.110582
        doi: 10.1016/j.biopha.2020.110582

         id: cord-258614-7unadw41
     author: Ogidigo, Joyce Oloaigbe
      title: Natural phyto, compounds as possible noncovalent inhibitors against SARS-CoV2 protease: computational approach
       date: 2020-10-25
      words: 8459.0
  sentences: 416.0
      pages: 
     flesch: 47.0
      cache: ./cache/cord-258614-7unadw41.txt
        txt: ./txt/cord-258614-7unadw41.txt
    summary: Structure-based virtual screening and molecular dynamics (MD) simulation have been employed to study their inhibitory potential against the main protease (M(pro)) SARS-CoV-2. These phytocompounds showed strong and stable interactions with the active site amino acid residues of SARS-CoV-2 Mpro similar to the reference compound. Results obtained from this study showed that momordicine and momordiciode F2 exhibited good inhibition potential (best MMGBA-binding energies; −41.1 and −43.4 kcal/mol) against the M(pro) of SARS-CoV-2 when compared with FDA reference anti-viral drugs (Ribavirin, remdesivir and hydroxychloroquine). Thus, among the 86 phytocompounds and 3 antiviral drugs screened (Supplementary material Table S1 ), 6 phyto ligands exhibited appreciable binding energies against the SARS-CoV-2 M pro and strong interactions within the binding pocket. Analysis of the per-residue additional showed that studied compounds interact with these key amino acid residues in the active site of the main protease, suggesting that these phytocompounds could emerge as ideal candidate''s inhibitors against SARS-CoV-2 M pro and another virus protease.
   abstract: At present, there is no cure or vaccine for the devastating new highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has affected people globally. Herein, we identified potent phytocompounds from two antiviral plants Momordica charantia L. and Azadirachta indica used locally for the treatment of viral and parasitic infections. Structure-based virtual screening and molecular dynamics (MD) simulation have been employed to study their inhibitory potential against the main protease (M(pro)) SARS-CoV-2. A total of 86 compounds from M. charantia L. and A. indica were identified. The top six phytocompounds; momordicine, deacetylnimninene, margolonone, momordiciode F2, nimbandiol, 17-hydroxyazadiradione were examined and when compared with three FDA reference drugs (remdesivir, hydroxychloroquine and ribavirin). The top six ranked compounds and FDA drugs were then subjected to MD simulation and pharmacokinetic studies. These phytocompounds showed strong and stable interactions with the active site amino acid residues of SARS-CoV-2 Mpro similar to the reference compound. Results obtained from this study showed that momordicine and momordiciode F2 exhibited good inhibition potential (best MMGBA-binding energies; −41.1 and −43.4 kcal/mol) against the M(pro) of SARS-CoV-2 when compared with FDA reference anti-viral drugs (Ribavirin, remdesivir and hydroxychloroquine). Per-residue analysis, root mean square deviation and solvent-accessible surface area revealed that compounds interacted with key amino acid residues at the active site of the enzyme and showed good system stability. The results obtained in this study show that these phytocompounds could emerge as promising therapeutic inhibitors for the M(pro) of SARS-CoV-2. However, urgent trials should be conducted to validate this outcome. Communicated by Ramaswamy H. Sarma
        url: https://www.ncbi.nlm.nih.gov/pubmed/33103616/
        doi: 10.1080/07391102.2020.1837681

         id: cord-349682-kpg0vley
     author: Ojha, Probir Kumar
      title: Therapeutics for COVID-19: from computation to practices—where we are, where we are heading to
       date: 2020-09-02
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: ABSTRACT: After the 1918 Spanish Flu pandemic caused by the H1N1 virus, the recent coronavirus disease 2019 (COVID-19) brought us to the time of serious global health catastrophe. Although no proven therapies are identified yet which can offer a definitive treatment of the COVID-19, a series of antiviral, antibacterial, antiparasitic, immunosuppressant drugs have shown clinical benefits based on repurposing theory. However, these studies are made on small number of patients, and, in majority of the cases, have been carried out as nonrandomized trials. As society is running against the time to combat the COVID-19, we present here a comprehensive review dealing with up-to-date information of therapeutics or drug regimens being utilized by physicians to treat COVID-19 patients along with in-depth discussion of mechanism of action of these drugs and their targets. Ongoing vaccine trials, monoclonal antibodies therapy and convalescent plasma treatment are also discussed. Keeping in mind that computational approaches can offer a significant insight to repurposing based drug discovery, an exhaustive discussion of computational modeling studies is performed which can assist target-specific drug discovery. GRAPHIC ABSTRACT: [Image: see text]
        url: https://www.ncbi.nlm.nih.gov/pubmed/32880078/
        doi: 10.1007/s11030-020-10134-x

         id: cord-317971-kuwargnp
     author: Opatz, Till
      title: Thoughts on What Chemists Can Contribute to Fighting SARS‐CoV‐2 – A Short Note on Hand Sanitizers, Drug Candidates and Outreach
       date: 2020-05-08
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The SARS‐CoV‐2 outbreak causing the respiratory disease COVID‐19 has left many chemists in academia without an obvious option to contribute to fighting the pandemic. Some of our recent experiences indicate that there are ways to overcome this dilemma. A three‐pronged approach is proposed.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32329159/
        doi: 10.1002/anie.202004721

         id: cord-033723-jy5fdsp9
     author: Orhobor, Oghenejokpeme I.
      title: Generating Explainable and Effective Data Descriptors Using Relational Learning: Application to Cancer Biology
       date: 2020-09-19
      words: 4013.0
  sentences: 229.0
      pages: 
     flesch: 52.0
      cache: ./cache/cord-033723-jy5fdsp9.txt
        txt: ./txt/cord-033723-jy5fdsp9.txt
    summary: In many scientific problems explainable models are required, and the input data is semantically complex and unsuitable for DNNs. This is true in the fundamental problem of understanding the mechanism of cancer drugs, which requires complex background knowledge about the functions of genes/proteins, their cells, and the molecular structure of the drugs. This has changed with the success of deep neural-networks (DNNs), which has been based on their capacity to utilize multiple neural network layers, and large amounts of data, to learn how to convert raw propositional descriptors (e.g., image pixel values) into richer internal representations that are effective for learning. We hypothesized that we could improve both ML model explainability, and predictive accuracy, by including additional background knowledge in the learning process using a hybrid RL approach. Furthermore, there exist several other approaches for learning representations from graph or inherently relational data [3, 13] with varying levels of predictive performance and interpretability.
   abstract: The key to success in machine learning is the use of effective data representations. The success of deep neural networks (DNNs) is based on their ability to utilize multiple neural network layers, and big data, to learn how to convert simple input representations into richer internal representations that are effective for learning. However, these internal representations are sub-symbolic and difficult to explain. In many scientific problems explainable models are required, and the input data is semantically complex and unsuitable for DNNs. This is true in the fundamental problem of understanding the mechanism of cancer drugs, which requires complex background knowledge about the functions of genes/proteins, their cells, and the molecular structure of the drugs. This background knowledge cannot be compactly expressed propositionally, and requires at least the expressive power of Datalog. Here we demonstrate the use of relational learning to generate new data descriptors in such semantically complex background knowledge. These new descriptors are effective: adding them to standard propositional learning methods significantly improves prediction accuracy. They are also explainable, and add to our understanding of cancer. Our approach can readily be expanded to include other complex forms of background knowledge, and combines the generality of relational learning with the efficiency of standard propositional learning.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556385/
        doi: 10.1007/978-3-030-61527-7_25

         id: cord-292041-a65kfw80
     author: Orienti, Isabella
      title: Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment in COVID-19
       date: 2020-05-27
      words: 6110.0
  sentences: 334.0
      pages: 
     flesch: 34.0
      cache: ./cache/cord-292041-a65kfw80.txt
        txt: ./txt/cord-292041-a65kfw80.txt
    summary: At present, there is no vaccine or effective standard treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (or coronavirus disease-19 (COVID-19)), which frequently leads to lethal pulmonary inflammatory responses. Therefore, due to its poly-pharmacology, fenretinide administration by pulmonary formulations may be expected to be protective against acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) caused by SARS-CoV infection and could represent a useful tool in a multimodal therapy aimed at establishing a rapid anti-inflammatory and antiviral effect. Pulmonary delivery of fenretinide could be a valuable tool in COVID-19 due to the possibility of obtaining a very high drug concentration in the airway and alveolar epithelia, thus triggering a rapid onset of local anti-inflammatory response. Moreover, the pulmonary administration of fenretinide, in combination with the drugs that are currently used in SARS-CoV-2 infection, could represent a new, effective tool in COVID-19 treatment.
   abstract: At present, there is no vaccine or effective standard treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (or coronavirus disease-19 (COVID-19)), which frequently leads to lethal pulmonary inflammatory responses. COVID-19 pathology is characterized by extreme inflammation and amplified immune response with activation of a cytokine storm. A subsequent progression to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can take place, which is often followed by death. The causes of these strong inflammatory responses in SARS-CoV-2 infection are still unknown. As uncontrolled pulmonary inflammation is likely the main cause of death in SARS-CoV-2 infection, anti-inflammatory therapeutic interventions are particularly important. Fenretinide N-(4-hydroxyphenyl) retinamide is a bioactive molecule characterized by poly-pharmacological properties and a low toxicity profile. Fenretinide is endowed with antitumor, anti-inflammatory, antiviral, and immunomodulating properties other than efficacy in obesity/diabetic pathologies. Its anti-inflammatory and antiviral activities, in particular, could likely have utility in multimodal therapies for the treatment of ALI/ARDS in COVID-19 patients. Moreover, fenretinide administration by pulmonary delivery systems could further increase its therapeutic value by carrying high drug concentrations to the lungs and triggering a rapid onset of activity. This is particularly important in SARS-CoV-2 infection, where only a narrow time window exists for therapeutic intervention.
        url: https://doi.org/10.3390/ijms21113812
        doi: 10.3390/ijms21113812

         id: cord-285603-f4572w5m
     author: Ortega, Joseph T.
      title: Class A G Protein-Coupled Receptor Antagonist Famotidine as a Therapeutic Alternative against SARS-CoV2: An In Silico Analysis
       date: 2020-06-24
      words: 5994.0
  sentences: 348.0
      pages: 
     flesch: 47.0
      cache: ./cache/cord-285603-f4572w5m.txt
        txt: ./txt/cord-285603-f4572w5m.txt
    summary: In order to gain a deeper understanding if the pharmacokinetic parameters of the SARS-CoV2 protease inhibitors could be related to positive outcomes in the therapy, we analyzed the ADME parameters of famotidine and compared with several known antiviral drugs such as ribavirin, lopinavir, and nafamostat, which were evaluated against SARS-CoV2. Chemical structures and administration, distribution, metabolism, and elimination (ADME) parameters for famotidine, ribavirin, lopinavir, and nafamostat, drugs that were evaluated as SARS-CoV2 inhibitors, are shown. Chemical structures and administration, distribution, metabolism, and elimination (ADME) parameters for famotidine, ribavirin, lopinavir, and nafamostat, drugs that were evaluated as SARS-CoV2 inhibitors, are shown. Altogether, in this study, we showed that famotidine could be used as an antiviral agent against SARS-CoV2, targeting proteases involved in the virus replication, mostly the main protease, as well as the viral PLpro and human host Tmprss2.
   abstract: The pandemic associated with Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV2) and its disease named COVID-19 challenged the scientific community to discover effective therapeutic solutions in a short period. Repurposing existing drugs is one viable approach that emphasizes speed during these urgent times. Famotidine, a class A G protein-coupled receptor antagonist used for the treatment of gastroesophageal reflux was recently identified in an in silico screening. Additionally, a recent retrospective clinical report showed that the treatment with famotidine provided a good outcome in patients infected with SARS-CoV2. A clinical trial testing effectiveness of famotidine in combination with hydroxychloroquine is currently ongoing in the United States (US). In the 1990s, famotidine was described as an antiviral agent against human immunodeficiency virus (HIV). Interestingly, some HIV protease inhibitors are presently being used against SARS-CoV2. However, it is not clear if famotidine could be effective against SARS-CoV2. Thus, by using a computational analysis, we aimed to examine if the antiviral effect of famotidine could be related to the inhibition of proteases involved in the virus replication. Our results showed that famotidine could interact within the catalytic site of the three proteases associated with SARS-CoV2 replication. However, weak binding affinity of famotidine to these proteases suggests that a successful famotidine therapy could likely be achieved only in combination with other antiviral drugs. Finally, analysis of famotidine’s pharmacokinetic parameters indicated that its effect against SARS-CoV2 infection could be reached only upon intravenous administration. This work will contribute to the pharmacological knowledge of famotidine as an antiviral agent against SARS-CoV2.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32599963/
        doi: 10.3390/biom10060954

         id: cord-265699-0socw0hp
     author: Ortega, Miguel Ángel
      title: Dendrimers and Dendritic Materials: From Laboratory to Medical Practice in Infectious Diseases
       date: 2020-09-14
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Infectious diseases are one of the main global public health risks, predominantly caused by viruses, bacteria, fungi, and parasites. The control of infections is founded on three main pillars: prevention, treatment, and diagnosis. However, the appearance of microbial resistance has challenged traditional strategies and demands new approaches. Dendrimers are a type of polymeric nanoparticles whose nanometric size, multivalency, biocompatibility, and structural perfection offer boundless possibilities in multiple biomedical applications. This review provides the reader a general overview about the uses of dendrimers and dendritic materials in the treatment, prevention, and diagnosis of highly prevalent infectious diseases, and their advantages compared to traditional approaches. Examples of dendrimers as antimicrobial agents per se, as nanocarriers of antimicrobial drugs, as well as their uses in gene transfection, in vaccines or as contrast agents in imaging assays are presented. Despite the need to address some challenges in order to be used in the clinic, dendritic materials appear as an innovative tool with a brilliant future ahead in the clinical management of infectious diseases and many other health issues.
        url: https://doi.org/10.3390/pharmaceutics12090874
        doi: 10.3390/pharmaceutics12090874

         id: cord-354006-j1y42oxu
     author: Ozdemir, Vural
      title: Shifting emphasis from pharmacogenomics to theragnostics
       date: 2006
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: What will be the role of theragnostic patents in upstream and downstream biomarker research?
        url: https://www.ncbi.nlm.nih.gov/pubmed/16900136/
        doi: 10.1038/nbt0806-942

         id: cord-261311-j6bmgmhz
     author: Parreiras Martins, Maria Auxiliadora
      title: Preparedness of pharmacists to respond to the emergency of the COVID-19 pandemic in Brazil: a comprehensive overview
       date: 2020-07-31
      words: 4307.0
  sentences: 206.0
      pages: 
     flesch: 37.0
      cache: ./cache/cord-261311-j6bmgmhz.txt
        txt: ./txt/cord-261311-j6bmgmhz.txt
    summary: COVID-19 patients may present high risk in the use of medications and clinical pharmacists can contribute substantially as part of a multidisciplinary team to improve outcomes in drug therapy in severe and critical illness. The course of an intense inflammatory process leads to alterations in many Review of patients'' medical history Provision of real-time assessment and evidence-based (when possible) advice on drug therapy Support on safe use of medications brought from home Medication reconciliation at different levels of transition of care Simplification of drug administration schedule to reduce the exposure of nurses to COVID-19 patients Monitoring of potential drug-drug, drug-food interactions and adverse drug reactions Adjustments in dosing regimens according to liver and kidney functions Prevention of medication errors Optimization of drug therapy and electrolytes to minimize the risk of prolonged corrected QT intervals and torsade de pointes Support on lung-protective ventilation and neuromuscular blocking agents to facilitate ventilator synchrony Provision of conservative fluid strategies and monitoring of vasopressors use Monitoring of empirical antibiotics for suspected bacterial co-infection with rigorous de-escalation Employment of FASTHUG-MAIDENS mnemonic to identify drug-related problems in intensive care units Support on drug information to patients and multidisciplinary teams, following biosafety protocols Considerations on special situations (pediatrics, older adults, people with chronic diseases, allergies) Research and continuing education Precise documentation of pharmaceutical interventions laboratory tests in patients with acute or severe/critical illness.
   abstract: The outbreak of COVID-19 in low- and middle-income countries is worrisome due to the social inequalities in these countries, their limited health budgets and the significant burden of other acute and chronic diseases. The leap in the number of cases in Brazil has imposed a huge strain on the healthcare system. We sought to provide a comprehensive overview of the challenges encountered by pharmacy services in responding to the COVID-19 pandemic emergency in Brazil and discuss the role of clinical pharmacists in this context. Pharmaceutical services play a key role in the emergency response to the pandemic. The pharmacy workforce has been actively working to manage drug shortages, redesign workflow, and review drug formularies/protocols to improve safety for patients and healthcare professionals (HCPs). COVID-19 patients may present high risk in the use of medications and clinical pharmacists can contribute substantially as part of a multidisciplinary team to improve outcomes in drug therapy in severe and critical illness. The participation of pharmacists as members of antimicrobial stewardship programs should be enhanced to ensure appropriate and safe use of antibiotics in this context. HCPs should be encouraged to seek improvements in the performance of pharmaceutical services and innovative practices to respond to the pandemic. Further studies are needed to generate knowledge on COVID-19 to improve patient care in vulnerable populations.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32837194/
        doi: 10.1007/s40267-020-00761-7

         id: cord-332038-icyut3xa
     author: Pillaiyar, Thanigaimalai
      title: A medicinal chemistry perspective of drug repositioning: Recent advances and challenges in drug discovery
       date: 2020-04-02
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Drug repurposing is a strategy consisting of finding new indications for already known marketed drugs used in various clinical settings or highly characterized compounds despite they can be failed drugs. Recently, it emerges as an alternative approach for the rapid identification and development of new pharmaceuticals for various rare and complex diseases for which lack the effective drug treatments. The success rate of drugs repurposing approach accounts for approximately 30% of new FDA approved drugs and vaccines in recent years. This review focuses on the status of drugs repurposing approach for various diseases including skin diseases, infective, inflammatory, cancer, and neurodegenerative diseases. Efforts have been made to provide structural features and mode of actions of drugs.
        url: https://www.sciencedirect.com/science/article/pii/S0223523420302440?v=s5
        doi: 10.1016/j.ejmech.2020.112275

         id: cord-001470-hn288o97
     author: Pivette, Mathilde
      title: Drug sales data analysis for outbreak detection of infectious diseases: a systematic literature review
       date: 2014-11-18
      words: 4423.0
  sentences: 260.0
      pages: 
     flesch: 50.0
      cache: ./cache/cord-001470-hn288o97.txt
        txt: ./txt/cord-001470-hn288o97.txt
    summary: CONCLUSIONS: Drug sales data analyses appear to be a useful tool for surveillance of gastrointestinal and respiratory disease, and OTC drugs have the potential for early outbreak detection. Published articles were searched for on electronic databases (Pubmed, Embase, Scopus, LILACS, African Index Medicus, Cochrane Library), using combinations of the following key words: ("surveillance" OR outbreak detection OR warning system) AND (overthe-counter OR "prescription drugs" OR pharmacy OR (pharmaceutical OR drug OR medication) sales). Articles excluded based on fulltext review (no drug sales data, no infectious disease, no outbreak detection) N= 85 Figure 1 Flow chart of study selection process in a systematic review of drug sales data analysis for syndromic surveillance of infectious diseases. Nineteen of the 27 studies were descriptive retrospective studies assessing the strength of the correlation between drug sales and reference surveillance data of the corresponding disease or evaluating outbreak-detection performance [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] .
   abstract: BACKGROUND: This systematic literature review aimed to summarize evidence for the added value of drug sales data analysis for the surveillance of infectious diseases. METHODS: A search for relevant publications was conducted in Pubmed, Embase, Scopus, Cochrane Library, African Index Medicus and Lilacs databases. Retrieved studies were evaluated in terms of objectives, diseases studied, data sources, methodologies and performance for real-time surveillance. Most studies compared drug sales data to reference surveillance data using correlation measurements or indicators of outbreak detection performance (sensitivity, specificity, timeliness of the detection). RESULTS: We screened 3266 articles and included 27 in the review. Most studies focused on acute respiratory and gastroenteritis infections. Nineteen studies retrospectively compared drug sales data to reference clinical data, and significant correlations were observed in 17 of them. Four studies found that over-the-counter drug sales preceded clinical data in terms of incidence increase. Five studies developed and evaluated statistical algorithms for selecting drug groups to monitor specific diseases. Another three studies developed models to predict incidence increase from drug sales. CONCLUSIONS: Drug sales data analyses appear to be a useful tool for surveillance of gastrointestinal and respiratory disease, and OTC drugs have the potential for early outbreak detection. Their utility remains to be investigated for other diseases, in particular those poorly surveyed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0604-2) contains supplementary material, which is available to authorized users.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240820/
        doi: 10.1186/s12879-014-0604-2

         id: cord-295807-68sukdb1
     author: Quade, Bianca N.
      title: The therapeutic importance of acid-base balance
       date: 2020-10-09
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Baking soda and vinegar have been used as home remedies for generations and today we are only a mouse-click away from claims that baking soda, lemon juice, and apple cider vinegar are miracles cures for everything from cancer to COVID-19. Despite these specious claims, the therapeutic value of controlling acid-base balance is indisputable and is the basis of Food and Drug Administration-approved treatments for constipation, epilepsy, metabolic acidosis, and peptic ulcers. In this narrative review, we present evidence in support of the current and potential therapeutic value of countering local and systemic acid-base imbalances, several of which do in fact involve the administration of baking soda (sodium bicarbonate). Furthermore, we discuss the side effects of pharmaceuticals on acid-base balance as well as the influence of acid-base status on pharmacokinetic properties of drugs. Our review considers all major organs systems as well as information relevant to several clinical specialties such as anesthesiology, infectious disease, oncology, dentistry, and surgery.
        url: https://doi.org/10.1016/j.bcp.2020.114278
        doi: 10.1016/j.bcp.2020.114278

         id: cord-302312-1pm17l5d
     author: Quinteros, Daniela A.
      title: Therapeutic use of monoclonal antibodies: general aspects and challenges for drug delivery
       date: 2017-03-31
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Monoclonal antibodies are routinely used in several fields but the great challenge has been their use as therapeutic agents for the treatment of diseases, such as breast cancer, leukemia, asthma, macular degeneration, arthritis, Crohn’s disease, and transplants, among others. Monoclonal antibodies are protein molecules made in the laboratory from hybridoma cells by recombinant DNA technology. Important advances have been made over the past decade to improve some critical points, such as safety and efficacy of the first generation of therapeutic antibodies. This type of molecules presents a significant challenge from the pharmaceutical point of view due to their characteristics, such as molecular size, stability, and solubility. In this chapter we have attempted to identify the major issues associated with therapeutic approaches, formulating drawbacks and delivering antibody drugs, particularly focused on the challenges and opportunities that these present for the future.
        url: https://api.elsevier.com/content/article/pii/B9780323461436000257
        doi: 10.1016/b978-0-323-46143-6.00025-7

         id: cord-293860-6kz0iws6
     author: Qutayba Almerie, Muhammad
      title: The Association between Obesity and Poor Outcome after COVID-19 Indicates a Potential Therapeutic Role for Montelukast
       date: 2020-05-27
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: It is widely believed that infection with the SARS-CoV2 virus triggers a disproportionate immune response which causes a devastating systemic injury, particularly in individuals with obesity, itself a chronic, multi-organ inflammatory disease. Immune cells accumulate in visceral adipose tissue and together with paracrine adipocytes release a wide range of biologically active cytokines (including IL-1β, IL5, IL6 and IL8) that can result in both local, pulmonary and systemic inflammation. A more intense ‘cytokine storm’ is postulated as the mechanism behind the extreme immune response seen in severe COVID-19. It is striking how dangerous the combination of obesity and COVID-19 is, resulting in a greater risk of ICU admission and a higher mortality. Furthermore, patients from a BAME background appear to have increased mortality after SARS-CoV2 infection; they also have a higher prevalence of central obesity and its metabolic complications. In the absence of an effective vaccine, the therapeutic potential of immune-modulating drugs is a priority, but the development of new drugs is expensive and time-consuming. A more pragmatic solution would be to seek to repurpose existing drugs, particularly those that might suppress the heightened cytokine activity seen in obesity, the major risk factor for a poor prognosis in COVID-19. Montelukast is a cysteinyl leukotriene receptor antagonist licensed to treat asthma and allergic rhinitis. It has been shown to diminish pulmonary response to antigen, tissue eosinophilia and IL-5 expression in inflammatory cells. It has also been shown to decrease elevated levels of IL-1β and IL8 in humans with viral upper respiratory tract infections compared with placebo-treated patients. In addition, in silico studies have demonstrated a high binding affinity of the montelukast molecule to the terminal site of the virus’s main protease enzyme which is needed for virus RNA synthesis and replication. Montelukast, which is cheap, safe and widely available would appear to have the potential to be an ideal candidate drug for clinical trials, particularly in early stage disease before irreparable tissue damage has already occurred. HYPOTHESIS: Through a direct anti-viral effect, or by suppression of heightened cytokine release in response to SARS-CoV2, montelukast will reduce the severity of immune-mediated multiorgan damage resulting from COVID-19, particularly in patients with central obesity and metabolic syndrome.
        url: https://www.sciencedirect.com/science/article/pii/S0306987720311488?v=s5
        doi: 10.1016/j.mehy.2020.109883

         id: cord-264867-ezsy76mx
     author: Rahman, Hamidur
      title: The recent advancement of low-dimensional nanostructured materials for drug delivery and drug sensing application: A brief review
       date: 2020-09-30
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: In this review article, we have presented a detailed analysis of the recent advancement of quantum mechanical calculations in the applications of the low-dimensional nanomaterials (LDNs) into biomedical fields like biosensors and drug delivery systems development. Biosensors play an essential role for many communities, e.g. law enforcing agencies to sense illicit drugs, medical communities to remove overdosed medications from the human and animal body etc. Besides, drug delivery systems are theoretically being proposed for many years and experimentally found to deliver the drug to the targeted sites by reducing the harmful side effects significantly. In current COVID-19 pandemic, biosensors can play significant roles, e.g. to remove experimental drugs during the human trials if they show any unwanted adverse effect etc. where the drug delivery systems can be potentially applied to reduce the side effects. But before proceeding to these noble and expensive translational research works, advanced theoretical calculations can provide the possible outcomes with considerable accuracy. Hence in this review article, we have analyzed how theoretical calculations can be used to investigate LDNs as potential biosensor devices or drug delivery systems. We have also made a very brief discussion on the properties of biosensors or drug delivery systems which should be investigated for the biomedical applications and how to calculate them theoretically. Finally, we have made a detailed analysis of a large number of recently published research works where theoretical calculations were used to propose different LDNs for bio-sensing and drug delivery applications.
        url: https://doi.org/10.1016/j.molliq.2020.114427
        doi: 10.1016/j.molliq.2020.114427

         id: cord-328705-024y5k72
     author: Rahman, Md. Mahbubur
      title: Virtual screening, molecular dynamics and structure–activity relationship studies to identify potent approved drugs for Covid-19 treatment
       date: 2020-07-21
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Computer-aided drug screening by molecular docking, molecular dynamics (MD) and structural–activity relationship (SAR) can offer an efficient approach to identify promising drug repurposing candidates for COVID-19 treatment. In this study, computational screening is performed by molecular docking of 1615 Food and Drug Administration (FDA) approved drugs against the main protease (Mpro) of SARS-CoV-2. Several promising approved drugs, including Simeprevir, Ergotamine, Bromocriptine and Tadalafil, stand out as the best candidates based on their binding energy, fitting score and noncovalent interactions at the binding sites of the receptor. All selected drugs interact with the key active site residues, including His41 and Cys145. Various noncovalent interactions including hydrogen bonding, hydrophobic interactions, pi–sulfur and pi–pi interactions appear to be dominant in drug–Mpro complexes. MD simulations are applied for the most promising drugs. Structural stability and compactness are observed for the drug–Mpro complexes. The protein shows low flexibility in both apo and holo form during MD simulations. The MM/PBSA binding free energies are also measured for the selected drugs. For pattern recognition, structural similarity and binding energy prediction, multiple linear regression (MLR) models are used for the quantitative structural–activity relationship. The binding energy predicted by MLR model shows an 82% accuracy with the binding energy determined by molecular docking. Our details results can facilitate rational drug design targeting the SARS-CoV-2 main protease. Communicated by Ramaswamy H. Sarma
        url: https://doi.org/10.1080/07391102.2020.1794974
        doi: 10.1080/07391102.2020.1794974

         id: cord-199630-2lmwnfda
     author: Ray, Sumanta
      title: Predicting potential drug targets and repurposable drugs for COVID-19 via a deep generative model for graphs
       date: 2020-07-05
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Coronavirus Disease 2019 (COVID-19) has been creating a worldwide pandemic situation. Repurposing drugs, already shown to be free of harmful side effects, for the treatment of COVID-19 patients is an important option in launching novel therapeutic strategies. Therefore, reliable molecule interaction data are a crucial basis, where drug-/protein-protein interaction networks establish invaluable, year-long carefully curated data resources. However, these resources have not yet been systematically exploited using high-performance artificial intelligence approaches. Here, we combine three networks, two of which are year-long curated, and one of which, on SARS-CoV-2-human host-virus protein interactions, was published only most recently (30th of April 2020), raising a novel network that puts drugs, human and virus proteins into mutual context. We apply Variational Graph AutoEncoders (VGAEs), representing most advanced deep learning based methodology for the analysis of data that are subject to network constraints. Reliable simulations confirm that we operate at utmost accuracy in terms of predicting missing links. We then predict hitherto unknown links between drugs and human proteins against which virus proteins preferably bind. The corresponding therapeutic agents present splendid starting points for exploring novel host-directed therapy (HDT) options.
        url: https://arxiv.org/pdf/2007.02338v1.pdf
        doi: nan

         id: cord-009763-44fexcpt
     author: Reddy, Mynampati Akshitha
      title: Internet-of-Things-Enabled Dual-Channel Iontophoretic Drug Delivery System for Elderly Patient Medication Management
       date: 2020-03-01
      words: 5226.0
  sentences: 331.0
      pages: 
     flesch: 55.0
      cache: ./cache/cord-009763-44fexcpt.txt
        txt: ./txt/cord-009763-44fexcpt.txt
    summary: In this study, the development of an iontophoretic drug delivery device that could be controlled using a mobile is described. A mobile app was developed to control the two-channel iontophoretic device and to monitor the loose lead of the active and the passive patches. Taking the cue from the above discussion, a smartphone-based remote-controlled iontophoretic drug delivery device has been developed in this study. Eagle PCB design software was used for the designing of the PCB for the developed circuit of the iontophoretic device with loose-lead monitoring capability (see Fig. S2 available in the Supplemental Materials on the ASME Digital Collection). While doing the drug release study in the active mode, the iontophoretic device was put on using the developed mobile app. The components of the proposed device, namely, the signal generator, the iontophoretic setup, the loose-lead monitoring system, and the Android app based wireless control system, were tested for their proper functionality.
   abstract: Wireless controllers have found its application in the supervision of the patients in the hospitals. It is not only a valid issue for the developing countries but also for the developed countries. For this reason, scientists are working on the advancement of medical devices that are capable of decreasing the workload of health caregivers. In this study, the development of an iontophoretic drug delivery device that could be controlled using a mobile is described. For the purpose, hardware and a software module were developed. The hardware module consisted of a two-channel voltage-controlled constant current sources that were used for driving the iontophoretic device. A mobile app was developed to control the two-channel iontophoretic device and to monitor the loose lead of the active and the passive patches. In the case of detection of the loose lead, the specific iontophoretic channel was stopped. Further, the audio-visual indicator was developed for the detection of the detachment of the patches (loose lead). The device was tested in vitro by performing the drug release study using drug-loaded emulsion gels that were formulated.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164504/
        doi: 10.1115/1.4045933

         id: cord-351222-9bfchw4u
     author: Rollinger, Judith M.
      title: Virtual screening for the discovery of bioactive natural products
       date: 2008
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: In this survey the impact of the virtual screening concept is discussed in the field of drug discovery from nature. Confronted by a steadily increasing number of secondary metabolites and a growing number of molecular targets relevant in the therapy of human disorders, the huge amount of information needs to be handled. Virtual screening filtering experiments already showed great promise for dealing with large libraries of potential bioactive molecules. It can be utilized for browsing databases for molecules fitting either an established pharmacophore model or a three dimensional (3D) structure of a macromolecular target. However, for the discovery of natural lead candidates the application of this in silico tool has so far almost been neglected. There are several reasons for that. One concerns the scarce availability of natural product (NP) 3D databases in contrast to synthetic libraries; another reason is the problematic compatibility of NPs with modern robotized high throughput screening (HTS) technologies. Further arguments deal with the incalculable availability of pure natural compounds and their often too complex chemistry. Thus research in this field is time-consuming, highly complex, expensive and ineffective. Nevertheless, naturally derived compounds are among the most favorable source of drug candidates. A more rational and economic search for new lead structures from nature must therefore be a priority in order to overcome these problems. Here we demonstrate some basic principles, requirements and limitations of virtual screening strategies and support their applicability in NP research with already performed studies. A sensible exploitation of the molecular diversity of secondary metabolites however asks for virtual screening concepts that are interfaced with well-established strategies from classical pharmacognosy that are used in an effort to maximize their efficacy in drug discovery. Such integrated virtual screening workflows are outlined here and shall help to motivate NP researchers to dare a step towards this powerful in silico tool.
        url: https://www.ncbi.nlm.nih.gov/pubmed/18084917/
        doi: 10.1007/978-3-7643-8117-2_6

         id: cord-325315-m3do6t1j
     author: Rossi, Carlo Maria
      title: A case report of toxic epidermal necrolysis (TEN) in a patient with COVID-19 treated with hydroxychloroquine: are these two partners in crime?
       date: 2020-10-06
      words: 2540.0
  sentences: 152.0
      pages: 
     flesch: 45.0
      cache: ./cache/cord-325315-m3do6t1j.txt
        txt: ./txt/cord-325315-m3do6t1j.txt
    summary: Given the activation of the immune system syndrome induced by the virus and the widespread off-label use of this drug, we suggest a careful monitoring of skin and mucous membranes in all COVID-19 positive patients treated with hydroxychloroquine in order to early detect early signs of toxicities. Another salient aspect of the case is the favorable evolution of the patient given that this type of SCAR is typically associated with a bad prognosis [35] [36] [37] , even more so because the patient displayed all the negative typical prognostic factors also for COVID-19 [38] [39] [40] [41] , indeed the calculation of the severity-of-illness score for toxic epidermal necrolysis (SCORTEN) in our patient led to an estimated mortality rate of 58.3% (CI 36,6 -77,59) ( Table 2 ) [42, 43] .
   abstract: BACKGROUND: Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is the most Serious Cutaneous Adverse Reaction (SCAR) often with a fatal outcome. Coronavirus Disease (COVID-19) is caused by Severe Acute Respiratory Syndrome–Coronavirus—2 (SARS-COV2) and is an emergent pandemic for which no cure exist at the moment. Several drugs have been tried often with scant clinical evidence and safety. CASE PRESENTATION: Here we report the case of 78-years-old woman with cardiometabolic syndrome and COVID-19. A multidrug regimen including others hydroxychloroquine, antibiotics, dexamethasone and paracetamol, low-molecular-weight-heparin and potassium canrenoate was started. After almost 3 weeks, the patient started to display a violaceous rash initially involving the flexural folds atypical targetoid lesions and showing a very fast extension, blister formation and skin detachments of approximately 70% of the total body surface area and mucous membranes involvement consistent with toxic epidermal necrolysis (TEN). The ALDEN algorithm was calculated inserting all drugs given to the patient in the 28 days preceding the onset of the skin manifestations. The highest score retrieved was for hydroxychloroquine. Other less suspicious drugs were piperacillin/tazobactam, ceftriaxone and levofloxacin. CONCLUSIONS: To our knowledge, this is the first case of TEN in a patient suffering from COVID-19 probably associated with hydroxychloroquine. Given the activation of the immune system syndrome induced by the virus and the widespread off-label use of this drug, we suggest a careful monitoring of skin and mucous membranes in all COVID-19 positive patients treated with hydroxychloroquine in order to early detect early signs of toxicities.
        url: https://www.ncbi.nlm.nih.gov/pubmed/33033459/
        doi: 10.1186/s12948-020-00133-6

         id: cord-315702-pn8247j2
     author: Sahakijpijarn, Sawittree
      title: Development of Remdesivir as a Dry Powder for Inhalation by Thin Film Freezing
       date: 2020-09-22
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Remdesivir exhibits in vitro activity against SARS-CoV-2 and was granted approval for Emergency Use. To maximize delivery to the lungs, we formulated remdesivir as a dry powder for inhalation using thin film freezing (TFF). TFF produces brittle matrix nanostructured aggregates that are sheared into respirable low-density microparticles upon aerosolization from a passive dry powder inhaler. In vitro aerodynamic testing demonstrated that drug loading and excipient type affected the aerosol performance of remdesivir. Remdesivir combined with optimal excipients exhibited desirable aerosol performance (up to 93.0% FPF; 0.82μm MMAD). Remdesivir was amorphous after the TFF process, which benefitted drug dissolution in simulated lung fluid. TFF remdesivir formulations are stable after one-month storage at 25 °C/60%RH. In vivo pharmacokinetic evaluation showed that TFF-remdesivir-leucine was poorly absorbed into systemic circulation while TFF-remdesivir-Captisol® demonstrated increased systemic uptake compared to leucine. Remdesivir was hydrolyzed to the nucleoside analog GS-441524 in lung, and levels of GS-441524 were greater in lung with the leucine formulation compared to Captisol®. In conclusion, TFF technology produces high potency remdesivir dry powder formulations for inhalation suitable to treat patients with COVID-19 on an outpatient basis and earlier in the disease course where effective antiviral therapy can reduce related morbidity and mortality.
        url: https://doi.org/10.1101/2020.07.26.222109
        doi: 10.1101/2020.07.26.222109

         id: cord-321230-b5a1z14w
     author: Samji, Hasina
      title: Drug-related deaths in a population-level cohort of people living with and without hepatitis C virus in British Columbia, Canada
       date: 2020-10-19
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: BACKGROUND: The majority of new HCV infections in Canada occur in people who inject drugs. Thus, while curative direct antiviral agents (DAAs) herald a promising new era in hepatitis C virus (HCV) treatment, improving the lives and wellbeing of people living with HCV (PLHCV) must be considered in the context of reducing overdose-related harms and with a syndemic lens. We measure drug-related deaths (DRDs) among HCV-negative people and PLHCV in British Columbia (BC), Canada, and the impact of potent contaminants like fentanyl on deaths. METHODS: We identified DRDs among PLHCV and HCV-negative individuals from 2010 to 2018 in the BC Hepatitis Testers Cohort, a population-based dataset of ~1.7 million British Columbians comprising comprehensive administrative and clinical data. We estimated annual standardized liver- and drug-related mortality rates per 100,000 person-years (PY) and described the contribution of specific drugs, including fentanyl and its analogues, implicated in DRDs over time. RESULTS: DRDs constituted 20.1% of deaths among PLHCV and 4.7% of deaths among HCV-negative individuals; a 4.3-fold (95% confidence interval: 4.0-4.5) difference. Drug-related mortality overtook liver-related mortality for PLHCV in 2015 and HCV-negative individuals in 2016 and rose from 241.7 to 436.5 per 100,000 PY from 2010 to 2018 amongPLHCV and from 20.0 to 57.1 per 100,000 PY for HCV-negative individuals over the same period. The proportion of deaths attributable to drugs among PLHCV and HCV-negative individuals increased from 15.1% to 26.1% and 3.1% to 8.0%, in 2010 and 2018, respectively. The proportion of DRDs attributed solely to synthetic opioids such as fentanyl averaged across both groups increased from 2.1% in 2010 to 69.6% in 2017. Conclusion: Steep drug-related mortality increases among PLHCV and HCV-negative individuals over the last decade highlight the urgent need to address overdose-related drivers and harms in these populations using an integrated care approach.
        url: https://www.ncbi.nlm.nih.gov/pubmed/33091735/
        doi: 10.1016/j.drugpo.2020.102989

         id: cord-262442-kjgpriow
     author: Scalia, Santo
      title: Quercetin solid lipid microparticles: A flavonoid for inhalation lung delivery
       date: 2013-05-13
      words: 5525.0
  sentences: 310.0
      pages: 
     flesch: 53.0
      cache: ./cache/cord-262442-kjgpriow.txt
        txt: ./txt/cord-262442-kjgpriow.txt
    summary: The quercetin SLMs were characterised for morphology, drug loading (15.5% ± 0.6, which corresponded to an encapsulation efficiency of 71.4%), particle size distribution, response to humidity, crystallinity, thermal behaviour and in vitro respirable fraction. Furthermore, the toxicity and the in vitro transport of the SLMs on an air liquid interface model of the Calu-3 cell line were also investigated using a modified twin-stage impinger apparatus. RESULTS: Results showed that quercetin SLMs could be formulated as dry powder suitable for inhalation drug delivery (20.5 ± 3.3% fine particle fraction ⩽4.46 μm) that was absorbed, via a linear kinetic model across the Calu-3 monolayer (22.32 ± 1.51% over 4 h). A modified in vitro aerosol testing apparatus (twin stage impinger TSI, Radleys, Essex, UK) that allows the attachment of a Transwell containing Calu-3 epithelial cells was used to study the mechanis m of drug deposition, dissolution and diffusion/transp ort (Haghi et al., 2010 (Haghi et al., , 2012 .
   abstract: PURPOSE: The aim of the present work was to develop solid lipid microparticles (SLMs), as dry powders containing quercetin for direct administration to the lung. METHODS: Quercetin microparticles were prepared by o/w emulsification via a phase inversion technique, using tristearin as the lipid component and phosphatidylcholine as an emulsifier. The quercetin SLMs were characterised for morphology, drug loading (15.5% ± 0.6, which corresponded to an encapsulation efficiency of 71.4%), particle size distribution, response to humidity, crystallinity, thermal behaviour and in vitro respirable fraction. Furthermore, the toxicity and the in vitro transport of the SLMs on an air liquid interface model of the Calu-3 cell line were also investigated using a modified twin-stage impinger apparatus. RESULTS: Results showed that quercetin SLMs could be formulated as dry powder suitable for inhalation drug delivery (20.5 ± 3.3% fine particle fraction ⩽4.46 μm) that was absorbed, via a linear kinetic model across the Calu-3 monolayer (22.32 ± 1.51% over 4 h). In addition, quercetin SLMs were shown to be non-toxic at the concentrations investigated. Interestingly, no apical to basolateral transport of the micronised quercetin was observed over the period of study. CONCLUSIONS: These observations suggest quercetin diffusion was enhanced by the presence of the lipid/emulsifying excipients in the SLMs; however further studies are necessary to elucidate the exact mechanisms.
        url: https://www.ncbi.nlm.nih.gov/pubmed/23541500/
        doi: 10.1016/j.ejps.2013.03.009

         id: cord-309871-y17puao2
     author: Scherrmann, JM.
      title: Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy
       date: 2020-06-12
      words: 3905.0
  sentences: 189.0
      pages: 
     flesch: 33.0
      cache: ./cache/cord-309871-y17puao2.txt
        txt: ./txt/cord-309871-y17puao2.txt
    summary: title: Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy The first one is related to the inverted influx transport of ABCB1, meaning that the azithromycin molecules, in addition to their passive diffusional uptake, are actively captured and trapped inside the vesicles, even if the vesicular intraluminal pH increases and the percentage of protonic drug molecules decreases enabling the backward diffusion of neutral species to the cytosol (Fig. 1) . To sum up, the intracellular ABCB1 could represent a potent target for enhancing the antiviral and antiinflammatory activities of the aminoquinolines when lysosomotropic ABCB1 substrates like azithromycin or ciprofloxacin are combined. In conclusion, we hypothesize that the intracellular ABCB1 may serve as a possible new target for improving the effects of the aminoquinolines when co-administered with a lysosomotropic drug, such as azithromycin or ciprofloxacin in COVID-19 chemotherapy.
   abstract: The co-administration of hydroxychloroquine with azithromycin is proposed in COVID-19 therapy. We hypothesize a new mechanism supporting the synergistic interaction between these drugs. Azithromycin is a substrate of ABCB1 (P-glycoprotein) which is localized in endosomes and lysosomes with a polarized substrate transport from the cell cytosol into the vesicle interior. SARS-CoV-2 and drugs meet in these acidic organelles and both basic drugs, which are potent lysosomotropic compounds, will become protonated and trapped within these vesicles. Consequently, their intra-vesicular concentrations can attain low micromolar effective cytotoxic concentrations on SARS-CoV-2 while concomitantly increase the intra-vesicular pH up to around neutrality. This last effect inhibits lysosomal enzyme activities responsible in virus entry and replication cycle. Based on these considerations, we hypothesize that ABCB1 could be a possible enhancer by confining azithromycin more extensively than expected when the trapping is solely dependent on the passive diffusion. This additional mechanism may therefore explain the synergistic effect when azithromycin is added to hydroxychloroquine, leading to apparently more rapid virus clearance and better clinical benefit, when compared to monotherapy with hydroxychloroquine alone.
        url: https://doi.org/10.1208/s12248-020-00465-w
        doi: 10.1208/s12248-020-00465-w

         id: cord-006479-iaocovf2
     author: Schreiber, J.
      title: Medikamenteninduzierte parenchymatöse Lungenerkrankungen
       date: 2009-08-01
      words: 1825.0
  sentences: 214.0
      pages: 
     flesch: 34.0
      cache: ./cache/cord-006479-iaocovf2.txt
        txt: ./txt/cord-006479-iaocovf2.txt
    summary: In diesem Beitrag wird eine Übersicht über medikamentös induzierte Erkrankungen des Lungenparenchyms, aber auch Reaktionsmuster wie das nichtkardiogene Lungenödem, die diffuse alveoläre Hämorrhagie, das medikamenteninduzierte ARDS ("acute respiratory distress syndrome") und eosinophile Lungenparenchymerkrankungen gegeben. So ist beispielsweise die früher häufige Nitrofurantoinlunge heute selten geworden, eine früher ebenfalls häufige Goldlunge als Folge einer Therapie einer rheumatoiden Arthritis mit Goldpräparaten dürfte heute nicht mehr auftreten. Eine Schädigung des Lungenparenchyms durch Medikamente manifestiert sich meist, jedoch nicht immer in Form einer Alveolitis oder Lungenfibrose und kann durch eine Vielzahl von Arzneimitteln induziert werden (. Interstitial lung disease · Hemorrhage · Allergic reaction · Toxicity · Drug cessation Bei begründetem Verdacht ist eine Medikamentenkarenz und in Abhängigkeit vom Schweregrad der Reaktion eine Therapie mit Glukokortikosteroiden indiziert. Die pulmonale Toxizität von Zytostatika wird in eine früh, während der Therapie einsetzende ("early onset") Form (.
   abstract: Drug-induced alveolitis/pneumonitis and lung fibrosis are comparatively frequent manifestations of drug-induced damage to the respiratory system. These side effects rarely have pathognomonic features. Therefore, they are relevant differential diagnoses of naturally occurring pulmonary diseases. Side effects of drug therapy may mimic much of the clinical-radiological-pathological pattern of interstitial lung diseases; however, precise figures on the frequency of medicamentous induction of interstitial lung disorders are lacking. The diagnostics are based mainly on verifying a compatible disease pattern, excluding differential diagnoses, and assessing the temporal relationship and the consequences of drug abstention. Reexposure is rarely indicated. Strict elimination of the responsible drugs is the most important therapeutic measure. Additional drug therapy, mostly with glucocorticosteroids, may be indicated. This article summarizes the spectrum of drug-induced disorders of the lung parenchyma.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101887/
        doi: 10.1007/s10405-008-0294-9

         id: cord-342756-rgm9ffpk
     author: Senger, Mario Roberto
      title: COVID-19: molecular targets, drug repurposing and new avenues for drug discovery
       date: 2020-10-02
      words: 16108.0
  sentences: 1024.0
      pages: 
     flesch: 51.0
      cache: ./cache/cord-342756-rgm9ffpk.txt
        txt: ./txt/cord-342756-rgm9ffpk.txt
    summary: Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. In the following topic, we will review SARS-CoV-2 structure and mechanism of infection in order to discuss molecular targets from the virus or its human host that are being considered for drug repurposing and perhaps future development of new drugs. (128) Its role as a functional receptor of SARS-CoV-2 S protein in host cells makes this protein a potential drug target to treat COVID-19. (138) TMPRSS2 has a major role in SARS-CoV-2 cell entry and replication, and thus represents an interesting therapeutic target since its inhibitors could potentially block virus infection in its initial stages. (199) A robust preclinical drug discovery pipeline comprising in vitro, and in vivo models of SARS-CoV-2 infection is particularly important to identify new antivirals for human COVID-19 treatment.
   abstract: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious infection that may break the healthcare system of several countries. Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. Finally, we also discuss patent protection issues, cost effectiveness and scalability of synthetic routes for some of the most studied repurposing candidates since these are key aspects to meet global demand for COVID-19 treatment.
        url: https://www.ncbi.nlm.nih.gov/pubmed/33027420/
        doi: 10.1590/0074-02760200254

         id: cord-348102-k0s9j9sz
     author: Silvestris, Nicola
      title: On the Management of Drug Interactions in the Course of Concomitant Treatments for COVID-19 and Antineoplastic Agents
       date: 2020-07-21
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: nan
        url: https://doi.org/10.3389/fonc.2020.01340
        doi: 10.3389/fonc.2020.01340

         id: cord-270516-9ol1209i
     author: Singh, Bhupinder
      title: Functionalized carbon nanotubes and their promising applications in therapeutics and diagnostics
       date: 2016-04-15
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Carbon nanotubes (CNTs) have attracted much attention from researchers worldwide in recent years due to their high aspect ratio, high surface area, and excellent material properties, such as electrical and thermal conductivities and mechanical strength. These rolled-up seamless cylinders of graphene sheets possess nanosized hollow-tube-shaped structures. The CNTs can be single-walled, double-walled or multi-walled, depending upon the number of graphene layers from which a single nanotube is composed. The CNTs, favoring encapsulation of drug molecules or by possible attachment of theranostic agents on the nanotube walls, have enabled their use in controlled drug delivery, and in targeting of drug molecules to specific sites such as the lymphatic system, brain, ocular system, and cancerous tissue. This chapter provides an overview of various types of CNTs, methods utilized for their commercial production, and the functionalization approaches employed in drug-delivery applications. In addition, the chapter also endeavors to provide a thoughtful insight into the toxicity and regulatory concerns that need to be addressed before the CNTs can be launched in the market.
        url: https://www.sciencedirect.com/science/article/pii/B9780323417365000157
        doi: 10.1016/b978-0-323-41736-5.00015-7

         id: cord-017062-dkw2sugl
     author: Singh, Indu
      title: Delivery Systems for Lymphatic Targeting
       date: 2013-10-08
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The lymphatic system has a critical role in the immune system’s recognition and response to disease, and it is an additional circulatory system throughout the entire body. Most solid cancers primarily spread from the main site via the tumour’s surrounding lymphatics before haematological dissemination. Targeting drugs to lymphatic system is quite complicated because of its intricate physiology. Therefore, it tends to be an important target for developing novel therapeutics. Currently, nanocarriers have encouraged the lymphatic targeting, but still there are challenges of locating drugs and bioactives to specific sites, maintaining desired action and crossing all the physiological barriers. Lymphatic therapy using drug-encapsulated colloidal carriers especially liposomes and solid lipid nanoparticles emerges as a new technology to provide better penetration into the lymphatics where residual disease exists. Optimising the proper procedure, selecting the proper delivery route and target area and making use of surface engineering tool, better carrier for lymphotropic system can be achieved. Thus, new methods of delivering drugs and other carriers to lymph nodes are currently under investigation.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121534/
        doi: 10.1007/978-1-4614-9434-8_20

         id: cord-321379-7bpl5n3j
     author: Singh, Sweta
      title: Coronavirus disease 2019 drug discovery through molecular docking
       date: 2020-06-03
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Background: The dawn of the year 2020 witnessed the spread of the highly infectious and communicable disease coronavirus disease 2019 (COVID-19) globally since it was first reported in 2019. Severe acute respiratory syndrome coronavirus-2 is the main causative agent. In total, 3,096,626 cases and 217,896 deaths owing to COVID-19 were reported by 30th April, 2020 by the World Health Organization. This means infection and deaths show an exponential growth globally. In order to tackle this pandemic, it is necessary to find possible easily accessible therapeutic agents till an effective vaccine is developed. Methods: In this study, we present the results of molecular docking processes through high throughput virtual screening to analyze drugs recommended for the treatment of COVID-19. Results: Atovaquone, fexofenadine acetate (Allegra), ethamidindole, baicalin, glycyrrhetic acid, justicidin D, euphol, and curine are few of the lead molecules found after docking 129 known antivirals, antimalarial, antiparasitic drugs and 992 natural products. Conclusions: These molecules could act as an effective inhibitory drug against COVID-19.
        url: https://doi.org/10.12688/f1000research.24218.1
        doi: 10.12688/f1000research.24218.1

         id: cord-336554-n8n5ii5k
     author: Singh, Thakur Uttam
      title: Drug repurposing approach to fight COVID-19
       date: 2020-09-05
      words: 13032.0
  sentences: 690.0
      pages: 
     flesch: 44.0
      cache: ./cache/cord-336554-n8n5ii5k.txt
        txt: ./txt/cord-336554-n8n5ii5k.txt
    summary: Number of drugs such as remdesivir, favipiravir, ribavirin, lopinavir, ritonavir, darunavir, arbidol, chloroquine, hydroxychloroquine, tocilizumab and interferons have shown inhibitory effects against the SARS-CoV2 in-vitro as well as in clinical conditions. Outbreaks of novel emerging infections such as coronavirus disease 2019 (COVID19) have unique challenges in front of the health professionals to select appropriate therapeutics/pharmacological treatments in the clinical setup with very little time available for the new drug discovery [3] . Currently, with the lack of effective agents against SARS-CoV2 as well as public-health emergency, WHO has identified some therapies which doctors and researchers believe are the most promising, such as a combination of two HIV drugs (lopinavir and ritonavir), anti-malarial drugs (chloroquine and hydroxychloroquine), and an experimental antiviral compound remdesivir. Ribavirin at a dose rate of 500 mg 2-3 times/day in combination with other drugs such as lopinavir/ritonavir or interferon (IFN)-α through intravenous route for not more than 10 days made the SARS-CoV2 infected patients more resistant to respiratory distress syndrome as well as death [41] .
   abstract: Currently, there are no treatment options available for the deadly contagious disease, coronavirus disease 2019 (COVID-19). Drug repurposing is a process of identifying new uses for approved or investigational drugs and it is considered as a very effective strategy for drug discovery as it involves less time and cost to find a therapeutic agent in comparison to the de novo drug discovery process. The present review will focus on the repurposing efficacy of the currently used drugs against COVID-19 and their mechanisms of action, pharmacokinetics, dosing, safety, and their future perspective. Relevant articles with experimental studies conducted in-silico, in-vitro, in-vivo, clinical trials in humans, case reports, and news archives were selected for the review. Number of drugs such as remdesivir, favipiravir, ribavirin, lopinavir, ritonavir, darunavir, arbidol, chloroquine, hydroxychloroquine, tocilizumab and interferons have shown inhibitory effects against the SARS-CoV2 in-vitro as well as in clinical conditions. These drugs either act through virus-related targets such as RNA genome, polypeptide packing and uptake pathways or target host-related pathways involving angiotensin-converting enzyme-2 (ACE2) receptors and inflammatory pathways. Using the basic knowledge of viral pathogenesis and pharmacodynamics of drugs as well as using computational tools, many drugs are currently in pipeline to be repurposed. In the current scenario, repositioning of the drugs could be considered the new avenue for the treatment of COVID-19.
        url: https://doi.org/10.1007/s43440-020-00155-6
        doi: 10.1007/s43440-020-00155-6

         id: cord-298369-66ifwtlp
     author: Smith, Sherri A.
      title: Pharmacokinetic and Pharmacodynamic Considerations for Drugs Binding to Alpha-1-Acid Glycoprotein
       date: 2018-12-28
      words: 10621.0
  sentences: 491.0
      pages: 
     flesch: 46.0
      cache: ./cache/cord-298369-66ifwtlp.txt
        txt: ./txt/cord-298369-66ifwtlp.txt
    summary: The importance of plasma protein binding primarily resides in its impact on pharmacokinetic properties such as clearance (CL) and volume of distribution (V ss ), with serum albumin, lipoproteins and alpha-1 acid glycoprotein (AAG) being the major proteins involved in sequestering drugs in plasma (1) . While AAG represents a relatively small portion (~1-3%) of the total plasma proteins, compared to~60% composition of albumin, it can play a significant role in drug binding and pharmacokinetics (PK) (43) . Since AAG levels increase in most disease states (46) , drugs with a high affinity may demonstrate higher binding (lower fraction unbound, f u ) and altered PK properties (e.g. lower total CL), lower V ss . Effect of the plasticizer DEHP in blood collection bags on human plasma fraction unbound determination for Alpha-1-Acid Glycoprotein (AAG) binding drugs
   abstract: According to the free drug hypothesis only the unbound drug is available to act at physiological sites of action, and as such the importance of plasma protein binding primarily resides in its impact on pharmacokinetics and pharmacodynamics. Of the major plasma proteins, alpha-1-acid glycoprotein (AAG) represents an intriguing one primarily due to the high affinity, low capacity properties of this protein. In addition, there are marked species and age differences in protein expression, homology and drug binding affinity. As such, a thorough understanding of drug binding to AAG can help aid and improve the translation of pharmacokinetic/pharmacodynamic (PK/PD) relationships from preclinical species to human as well as adults to neonates. This review provides a comprehensive overview of our current understanding of the biochemistry of AAG; endogenous function, impact of disease, utility as a biomarker, and impact on PK/PD. Experimental considerations are discussed as well as recommendations for understanding the potential impact of AAG on PK through drug discovery and early development.
        url: https://www.ncbi.nlm.nih.gov/pubmed/30593605/
        doi: 10.1007/s11095-018-2551-x

         id: cord-007798-9ht7cqhu
     author: Smith, Silas W.
      title: Drugs and pharmaceuticals: management of intoxication and antidotes
       date: 2010-02-25
      words: 22555.0
  sentences: 1371.0
      pages: 
     flesch: 34.0
      cache: ./cache/cord-007798-9ht7cqhu.txt
        txt: ./txt/cord-007798-9ht7cqhu.txt
    summary: In the context of analgesic, anti-inflammatory, anticholinergic, anticonvulsant, antihyperglycemic, antimicrobial, antineoplastic, cardiovascular, opioid, or sedative-hypnotic agents overdose, N-acetylcysteine, physostigmine, l-carnitine, dextrose, octreotide, pyridoxine, dexrazoxane, leucovorin, glucarpidase, atropine, calcium, digoxin-specific antibody fragments, glucagon, high-dose insulin euglycemia therapy, lipid emulsion, magnesium, sodium bicarbonate, naloxone, and flumazenil are specifically reviewed. As might be anticipated from the fact that supportive care suffices for the majority of poisoned patients, a typical study of routine administration of charcoal following oral overdose of primarily benzodiazepines, acetaminophen, and selective serotonin reuptake inhibitors could not demonstrate benefit [16, 17, 23] . Patient characteristics suggesting extracorporeal therapy include signs or symptoms of significant end organ toxicity; impaired elimination secondary to baseline comorbidities or critical illness-induced hypoperfusion; inability to tolerate or refractory to antidotal strategies (such as bicarbonate or saline); inadequate response to supportive care measures; concurrent electrolyte derangements (e.g., metformin-associated lactic acidosis); or serum drug concentrations historically associated with severe outcome [127] .
   abstract: The treatment of patients poisoned with drugs and pharmaceuticals can be quite challenging. Diverse exposure circumstances, varied clinical presentations, unique patient-specific factors, and inconsistent diagnostic and therapeutic infrastructure support, coupled with relatively few definitive antidotes, may complicate evaluation and management. The historical approach to poisoned patients (patient arousal, toxin elimination, and toxin identification) has given way to rigorous attention to the fundamental aspects of basic life suppport — airway management, oxygenation and ventilation, circulatory competence, thermoregulation, and substrate availability. Selected patients may benefit from methods to alter toxin pharmacokinetics to minimize systemic, target organ, or tissue compartment exposure (either by decreasing absorption or increasing elimination). These may include syrup of ipecac, orogastric lavage, activated single- or multi-dose charcoal, whole bowel irrigation, endoscopy and surgery, urinary alkalinization, saline diuresis, or extracorporeal methods (hemodialysis, charcoal hemoperfusion, continuous venovenous hemofiltration, and exchange transfusion). Pharmaceutical adjuncts and antidotes may be useful in toxicant-induced hyperthermias. In the context of analgesic, anti-inflammatory, anticholinergic, anticonvulsant, antihyperglycemic, antimicrobial, antineoplastic, cardiovascular, opioid, or sedative-hypnotic agents overdose, N-acetylcysteine, physostigmine, l-carnitine, dextrose, octreotide, pyridoxine, dexrazoxane, leucovorin, glucarpidase, atropine, calcium, digoxin-specific antibody fragments, glucagon, high-dose insulin euglycemia therapy, lipid emulsion, magnesium, sodium bicarbonate, naloxone, and flumazenil are specifically reviewed. In summary, patients generally benefit from aggressive support of vital functions, careful history and physical examination, specific laboratory analyses, a thoughtful consideration of the risks and benefits of decontamination and enhanced elimination, and the use of specific antidotes where warranted. Data supporting antidotes effectiveness vary considerably. Clinicians are encouraged to utilize consultation with regional poison centers or those with toxicology training to assist with diagnosis, management, and administration of antidotes, particularly in unfamiliar cases.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123602/
        doi: 10.1007/978-3-7643-8338-1_12

         id: cord-279106-3ffa9djf
     author: Syatila Ab Ghani, Nur
      title: Side chain similarity comparisons for integrated drug repositioning and potential toxicity assessments in epidemic response scenarios: the case for COVID-19
       date: 2020-10-21
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Structures of protein-drug-complexes provide an atomic level profile of drug-target interactions. In this work, the three-dimensional arrangements of amino acid side chains in known drug binding sites (substructures) were used to search for similarly arranged sites in SARS-CoV-2 protein structures in the Protein Data Bank for the potential repositioning of approved compounds. We were able to identify 22 target sites for the repositioning of 16 approved drug compounds as potential therapeutics for COVID-19. Using the same approach, we were also able to investigate the potentially promiscuous binding of the 16 compounds to off-target sites that could be implicated in toxicity and side effects that had not been provided by any previous studies. The investigations of binding properties in disease-related proteins derived from the comparison of amino acid substructure arrangements allows for effective mechanism driven decision making to rank and select only the compounds with the highest potential for success and safety to be prioritized for clinical trials or treatments. The intention of this work is not to explicitly identify candidate compounds but to present how an integrated drug repositioning and potential toxicity pipeline using side chain similarity searching algorithms are of great utility in epidemic scenarios involving novel pathogens. In the case of the COVID-19 pandemic caused by the SARS-CoV-2 virus, we demonstrate that the pipeline can identify candidate compounds quickly and sustainably in combination with associated risk factors derived from the analysis of potential off-target site binding by the compounds to be repurposed.
        url: https://www.ncbi.nlm.nih.gov/pubmed/33101604/
        doi: 10.1016/j.csbj.2020.10.013

         id: cord-352579-ndcbmgfj
     author: Takahashi, Takuto
      title: Pharmacogenomics of COVID-19 therapies
       date: 2020-08-18
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: A new global pandemic of coronavirus disease 2019 (COVID-19) has resulted in high mortality and morbidity. Currently numerous drugs are under expedited investigations without well-established safety or efficacy data. Pharmacogenomics may allow individualization of these drugs thereby improving efficacy and safety. In this review, we summarized the pharmacogenomic literature available for COVID-19 drug therapies including hydroxychloroquine, chloroquine, azithromycin, remdesivir, favipiravir, ribavirin, lopinavir/ritonavir, darunavir/cobicistat, interferon beta-1b, tocilizumab, ruxolitinib, baricitinib, and corticosteroids. We searched PubMed, reviewed the Pharmacogenomics Knowledgebase (PharmGKB(®)) website, Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, the U.S. Food and Drug Administration (FDA) pharmacogenomics information in the product labeling, and the FDA pharmacogenomics association table. We found several drug-gene variant pairs that may alter the pharmacokinetics of hydroxychloroquine/chloroquine (CYP2C8, CYP2D6, SLCO1A2, and SLCO1B1); azithromycin (ABCB1); ribavirin (SLC29A1, SLC28A2, and SLC28A3); and lopinavir/ritonavir (SLCO1B1, ABCC2, CYP3A). We also identified other variants, that are associated with adverse effects, most notable in hydroxychloroquine/chloroquine (G6PD; hemolysis), ribavirin (ITPA; hemolysis), and interferon β -1b (IRF6; liver toxicity). We also describe the complexity of the risk for QT prolongation in this setting because of additive effects of combining more than one QT-prolonging drug (i.e., hydroxychloroquine/chloroquine and azithromycin), increased concentrations of the drugs due to genetic variants, along with the risk of also combining therapy with potent inhibitors. In conclusion, although direct evidence in COVID-19 patients is lacking, we identified potential actionable genetic markers in COVID-19 therapies. Clinical studies in COVID-19 patients are deemed warranted to assess potential roles of these markers.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32864162/
        doi: 10.1038/s41525-020-00143-y

         id: cord-308994-4nljzm8a
     author: Tang, Zhongmin
      title: Insights from nanotechnology in COVID-19 treatment
       date: 2020-11-04
      words: 3239.0
  sentences: 177.0
      pages: 
     flesch: 36.0
      cache: ./cache/cord-308994-4nljzm8a.txt
        txt: ./txt/cord-308994-4nljzm8a.txt
    summary: We focus specifically on SARS-CoV-2 and the detailed role that nanotechnology can play in addressing this pandemic, including i) using FDA-approved nanomaterials for drug/vaccine delivery, including further exploration of the inhalation pathway; ii) introducing promising nanomaterials currently in clinical trials for drug/vaccine delivery; iii) designing novel biocompatible nanomaterials to combat the virus via interfering in its life cycle; and iv) promoting the utilization of nanomaterials in pneumonia treatment. To summarize, the advantages of nanotechnology in antiviral research include the following: 1) promotes the delivery of water-insoluble drugs; [39] 2) enhances the circulation time of drugs in vivo; [40] 3) achieves co-delivery of drugs; [40] 4) improves drug utilization efficiency and reduce side effects through targeting antibody modification; [41] 5) protects DNA and mRNA vaccines, overcoming bottlenecks for in vivo applications; [42] and 6) the physicochemical properties of nanomaterials can also be employed directly against viruses.
   abstract: In just a few months, SARS-CoV-2 and the disease it causes, COVID-19, created a worldwide pandemic. Virologists, biologists, pharmacists, materials scientists, and clinicians are collaborating to develop efficient treatment strategies. Overall, in addition to the use of clinical equipment to assist patient rehabilitation, antiviral drugs and vaccines are the areas of greatest focus. Given the physical size of SARS-CoV-2 and the vaccine delivery platforms currently in clinical trials, the relevance of nanotechnology is clear, and previous antiviral research using nanomaterials also supports this connection. Herein we briefly summarize current representative strategies regarding nanomaterials in antiviral research. We focus specifically on SARS-CoV-2 and the detailed role that nanotechnology can play in addressing this pandemic, including i) using FDA-approved nanomaterials for drug/vaccine delivery, including further exploration of the inhalation pathway; ii) introducing promising nanomaterials currently in clinical trials for drug/vaccine delivery; iii) designing novel biocompatible nanomaterials to combat the virus via interfering in its life cycle; and iv) promoting the utilization of nanomaterials in pneumonia treatment.
        url: https://www.ncbi.nlm.nih.gov/pubmed/33178330/
        doi: 10.1016/j.nantod.2020.101019

         id: cord-331633-ix5un6c9
     author: Teixeira, Maria C.
      title: Nanomedicines for the Delivery of Antimicrobial Peptides (AMPs)
       date: 2020-03-20
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Microbial infections are still among the major public health concerns since several yeasts and fungi, and other pathogenic microorganisms, are responsible for continuous growth of infections and drug resistance against bacteria. Antimicrobial resistance rate is fostering the need to develop new strategies against drug-resistant superbugs. Antimicrobial peptides (AMPs) are small peptide-based molecules of 5–100 amino acids in length, with potent and broad-spectrum antimicrobial properties. They are part of the innate immune system, which can represent a minimal risk of resistance development. These characteristics contribute to the description of these molecules as promising new molecules in the development of new antimicrobial drugs. However, efforts in developing new medicines have not resulted in any decrease of drug resistance yet. Thus, a technological approach on improving existing drugs is gaining special interest. Nanomedicine provides easy access to innovative carriers, which ultimately enable the design and development of targeted delivery systems of the most efficient drugs with increased efficacy and reduced toxicity. Based on performance, successful experiments, and considerable market prospects, nanotechnology will undoubtedly lead a breakthrough in biomedical field also for infectious diseases, as there are several nanotechnological approaches that exhibit important roles in restoring antibiotic activity against resistant bacteria.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32244858/
        doi: 10.3390/nano10030560

         id: cord-281561-r10y2sgb
     author: Tiwari, Nidhi
      title: Novel β-Coronavirus (SARS-CoV-2): Current and Future Aspects of Pharmacological Treatments
       date: 2020-08-27
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The novel coronavirus outbreak has reported to be rapidly spreading across the countries and becomes a foremost community health alarm. At present, no vaccine or specific drug is on hand for the treatment of this infectious disease. This review investigates the drugs, which are being evaluated and found to be effective against nCOVID-19 infection. A thorough literature search was performedon the recently published research papers in between January 2020 to May 2020, through various databases like “Science Direct”, “Google Scholar”, “PubMed”,“Medline”, “Web of Science”, and “World Health Organization (WHO)”. We reviewed and documented the information related with the current and future aspects for the management and cure of COVID-19. As of 21st July, 2020 a total of 14,562,550 confirmed cases of coronavirus and 607,781 deaths have been reported world-wide. The main clinical feature of COVID-19 ranges from asymptomatic disease to mild lower respiratory tract illness to severe pneumonia, acute lung injury, acute respiratory distress syndrome (ARDS), multiple organ dysfunction, and death. The drugs at present used in COVID-19 patients and ongoing clinical trials focusing on drug repurposing of various therapeutic classes of drug e.g. antiviral, anti-inflammatory and/or immunomodulatory drugs along with adjuvant/supportive care. Many drugs on clinical trials shows effective results on preliminary scale and now used currently in patients. Adjuvant/ supportive care therapy are used in patients to get the best results in order to minimize the short and long-term complications. However, further studies and clinical trials are needed on large scale of population to reach any firm conclusion in terms of its efficacy and safety.
        url: https://doi.org/10.1016/j.jsps.2020.08.015
        doi: 10.1016/j.jsps.2020.08.015

         id: cord-354180-6esn3t2b
     author: Tyndall, Mark
      title: Safer opioid distribution in response to the COVID-19 pandemic
       date: 2020-07-27
      words: 4223.0
  sentences: 221.0
      pages: 
     flesch: 57.0
      cache: ./cache/cord-354180-6esn3t2b.txt
        txt: ./txt/cord-354180-6esn3t2b.txt
    summary: The arrival of the COVID-19 pandemic comes at time when North America is in the midst of a protracted overdose epidemic caused by a toxic illegal drug supply. Overdose deaths are likely to rise when people are isolated, social support programs are cut back, and the illicit drug supply is further compromised. Safer opioid distribution in response to a toxic street drug supply is a pragmatic and effective way to reduce overdose deaths. Even if emergency housing can be found and mitigation strategies to reduce COVID-19 transmission are put in place, the need to access an illegal drug supply makes staying in place extremely unlikely (Bodkin et al., 2020) . A waning tolerance to opioids means that the first exposure to street drugs can be deadly and it is critical that proper discharge planning and supports are in place (Bukten et al.,2017) Many people who use drugs rely on public services for medical care, harm reduction supplies, street outreach, and food distribution.
   abstract: COVID-19 has turned the world upside down in a very short period of time. The impact of COVID-19 will disproportionately effect people who are least able to protect themselves and this will include people who use drugs. The arrival of the COVID-19 pandemic comes at time when North America is in the midst of a protracted overdose epidemic caused by a toxic illegal drug supply. Overdose deaths are likely to rise when people are isolated, social support programs are cut back, and the illicit drug supply is further compromised. Safer opioid distribution in response to a toxic street drug supply is a pragmatic and effective way to reduce overdose deaths. COVID-19 makes such an approach even more urgent and compelling.
        url: https://doi.org/10.1016/j.drugpo.2020.102880
        doi: 10.1016/j.drugpo.2020.102880

         id: cord-263312-x7f0hn7f
     author: Tzelepis, Ilias
      title: Drosophila melanogaster: a first step and a stepping-stone to anti-infectives
       date: 2013-08-28
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Following an expansion in the antibiotic drug discovery in the previous century, we now face a bottleneck in the production of new anti-infective drugs. Traditionally, chemical libraries are screened either using in vitro culture systems or in silico to identify and chemically modify small molecules with antimicrobial properties. Nevertheless, almost all compounds passing through in vitro screening fail to pass preclinical trials. Drug screening in Drosophila offers to fill the gap between in vitro and mammalian model host testing by eliminating compounds that are toxic or have reduced bioavailability and by identifying others that may boost innate host defence or selectively reduce microbial virulence in a whole-organism setting. Such alternative screening methods in Drosophila, while low-throughput, may reduce the cost and increase the success rate of preclinical trials.
        url: https://doi.org/10.1016/j.coph.2013.08.003
        doi: 10.1016/j.coph.2013.08.003

         id: cord-277535-u283k70i
     author: Vaja, Rakesh
      title: Drugs and the liver
       date: 2020-09-22
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The liver is a major organ with multiple functions. A number of drugs are metabolized by the liver during phase 1 and 2 reactions which include complex processes involving cytochrome P450 enzymes. Genetic and acquired variability in cytochrome P450 activity may have profound effects on pharmacokinetics. Additionally, drugs can also modify how the liver functions and cause dysfunction or even failure of the organ both by a direct effect on the liver or by alteration in liver blood flow. It is important to recognize the signs and symptoms of liver failure in patients and identify possible causes including drug interactions. Furthermore, once a patient has been recognized to be suffering with liver dysfunction or failure drug choice and dosing regime will need to be rationalized. Paracetamol overdose can have severe and life threatening consequences for patients due to its effect on liver function. It is the leading cause of acute liver failure in the UK, 1 Correct and early management is crucial and will be discussed within this article.
        url: https://api.elsevier.com/content/article/pii/S1472029920301399
        doi: 10.1016/j.mpaic.2020.07.001

         id: cord-003118-58ta20fg
     author: Van Norman, Gail A.
      title: Expanding Patient Access to Investigational New Drugs: Overview of Intermediate and Widespread Treatment Investigational New Drugs, and Emergency Authorization in Public Health Emergencies
       date: 2018-06-25
      words: 2205.0
  sentences: 109.0
      pages: 
     flesch: 46.0
      cache: ./cache/cord-003118-58ta20fg.txt
        txt: ./txt/cord-003118-58ta20fg.txt
    summary: Individual patients with life-threatening or severely debilitating diseases can petition the U.S. Food and Drug Administration (FDA) through their physicians to have expanded access (EA) to drugs that are in clinical trials but have not reached full FDA approval (the "single-patient" investigational new drug [IND] application). Spurred by patient advocacy during the early days of the acquired immunodeficiency syndrome (AIDS) epidemic in the late 1980s, and facilitated by subsequent legislative efforts over the next 20 years, regulatory initiatives permit the FDA to release drugs for use in individual patients through expanded access (EA) INDs (4, 5) , in many cases allowing emergency treatment with nonapproved drugs within hours of application, and nonemergency treatment within an average of 4 days (6) . Releasing investigational new drugs to individual patients who are facing certain death or disability seems to be a relatively uncomplicated decision, but allowing EA to entire groups of patients for treatment with an investigational new drug presents more complex regulatory, logistical, and ethical challenges for scientists, commercial entities, and the FDA.
   abstract: Individual patients with life-threatening or severely debilitating diseases can petition the U.S. Food and Drug Administration (FDA) through their physicians to have expanded access (EA) to drugs that are in clinical trials but have not reached full FDA approval (the “single-patient” investigational new drug [IND] application). Additionally, recent state and federal laws—so-called “right to try legislation”—allow patients to approach drug companies directly for access prior to FDA approval. While these pathways provide potential access for individual patients to investigational drugs, different EA pathways permit entire groups of certain patients to access investigational drugs prior to FDA approval. This review focuses on special categories of EA INDs intended for multiple patients—the intermediate-group IND and the widespread-treatment IND—as well as emergency authorization for use of investigational drugs and biological products (e.g., vaccines) in public health emergencies.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058931/
        doi: 10.1016/j.jacbts.2018.02.001

         id: cord-284648-yznlgzir
     author: Varanko, Anastasia
      title: Recent trends in protein and peptide-based biomaterials for advanced drug delivery
       date: 2020-08-29
      words: 33501.0
  sentences: 1732.0
      pages: 
     flesch: 42.0
      cache: ./cache/cord-284648-yznlgzir.txt
        txt: ./txt/cord-284648-yznlgzir.txt
    summary: Albumin is the most abundant protein in human plasma and has a set of properties that make it a unique molecular carrier for drugs: (i) it is a natural physiological carrier of native ligands and nutrients; (ii) it bypasses systemic clearance and degradation by the body''s own innate mechanisms, so that it has an exceptionally long half-life of 19 days in humans, and similarly long half-lives in most animal species [123] [124] [125] [126] ; (iii) it preferentially accumulates at sites of vascular leakiness; (iv) it is highly internalized and metabolized by rapidly growing, nutrient-starved cancer cells; and (v) it is biodegradable and has no known systemic toxicity. Other notable examples of albumin-based delivery systems involve the genetic fusion of ABD to various therapeutic proteins including affibodies [165, 166] , human soluble complement receptor type 1 [167] , single chain antibody-drug conjugates [168] , insulin-like growth factor II [169] , immunotoxins [170] , and respiratory syncytial virus subgroup A (RSV-A) G protein (G2Na) [171] .
   abstract: nan
        url: https://doi.org/10.1016/j.addr.2020.08.008
        doi: 10.1016/j.addr.2020.08.008

         id: cord-263803-0n41gylj
     author: Villoutreix, Bruno O.
      title: Prevention of COVID-19 by drug repurposing: rationale from drugs prescribed for mental disorders
       date: 2020-06-25
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pubmed/32593662/
        doi: 10.1016/j.drudis.2020.06.022

         id: cord-303237-xvba5mqq
     author: Wang, L.-Y.
      title: Genetic Profiles in Pharmacogenes Indicate Personalized Drug Therapy for COVID-19
       date: 2020-03-30
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Background: The coronavirus disease 2019 (COVID-19) has become a global pandemic currently. Many drugs showed potential for COVID-19 therapy. However, genetic factors which can lead to different drug efficiency and toxicity among populations are still undisclosed in COVID-19 therapy. Methods: We selected 67 potential drugs for COVID-19 therapy (DCTs) from clinical guideline and clinical trials databases. 313 pharmaco-genes related to these therapeutic drugs were included. Variation information in 125,748 exomes were collected for racial differences analyses. The expression level of pharmaco-genes in single cell resolution was evaluated from single-cell RNA sequencing (scRNA-seq) data of 17 healthy adults. Results: Pharmacogenes, including CYP3A4, ABCB1, SLCO1B1, ALB, CYP3A5, were involved in the process of more than multi DCTs. 224 potential drug-drug interactions (DDI) of DCTs were predicted, while 112 of them have been reported. Racial discrepancy of common nonsynonymous mutations was found in pharmacogenes including: VDR, ITPA, G6PD, CYP3A4 and ABCB1 which related to DCTs including ribavirin, -interferon, chloroquine and lopinavir. Moreover, ACE2, the target of 2019-nCoV, was only found in parts of lung cells, which makes drugs like chloroquine that prevent virus binding to ACE2 more specific than other targeted drugs such as camostat mesylate. Conclusions: At least 17 drugs for COVID-19 therapy with predictable pharmacogenes should be carefully utilized in risk races which are consisted of more risk allele carriers. At least 29 drugs with potential of DDIs are reported to be affected by other DDIs, they should be replaced by similar drugs without interaction if it is possible. Drugs which specifically targeted to infected cells with ACE2 such as chloroquine are preferred in COVID-19 therapy.
        url: https://doi.org/10.1101/2020.03.23.20041350
        doi: 10.1101/2020.03.23.20041350

         id: cord-103876-2rg2qtdq
     author: Watkins, Laura C.
      title: Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics
       date: 2020-06-20
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: Prevalent resistance to inhibitors that target the influenza A M2 proton channel has necessitated a continued drug design effort, supported by a sustained study of the mechanism of channel function and inhibition. Recent high-resolution X-ray crystal structures present the first opportunity to see how the adamantyl-amine class of inhibitors bind to M2 and disrupt and interact with the channel’s water network, providing insight into the critical properties that enable their effective inhibition in wildtype M2. In this work, we test the hypothesis that these drugs act primarily as mechanism-based inhibitors by comparing hydrated excess proton stabilization during proton transport in M2 with the interactions revealed in the crystal structures, using the Multiscale Reactive Molecular Dynamics (MS-RMD) methodology. MS-RMD, unlike classical molecular dynamics, models the hydrated proton (hydronium-like cation) as a dynamic excess charge defect and allows bonds to break and form, capturing the intricate interactions between the hydrated excess proton, protein atoms, and water. Through this, we show that the ammonium group of the inhibitors is effectively positioned to take advantage of the channel’s natural ability to stabilize an excess protonic charge and is thus acting as a hydronium-mimic. Additionally, we show that the channel is especially stable in the drug binding region, highlighting the importance of this property for binding the adamantane group. Finally, we characterize an additional hinge point near Val27, which dynamically responds to charge and inhibitor binding. Altogether, this work further illuminates a dynamic understanding of the mechanism of drug inhibition in M2, grounded in the fundamental properties that enable the channel to transport and stabilize excess protons, with critical implications for future drug design efforts. TOC Graphic
        url: https://doi.org/10.1101/2020.06.19.162248
        doi: 10.1101/2020.06.19.162248

         id: cord-304506-6el2ryl8
     author: Watkins, Laura C.
      title: Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics
       date: 2020-09-16
      words: 6140.0
  sentences: 277.0
      pages: 
     flesch: 45.0
      cache: ./cache/cord-304506-6el2ryl8.txt
        txt: ./txt/cord-304506-6el2ryl8.txt
    summary: In this work, we examine the hypothesis that these drugs act primarily as mechanism-based inhibitors by comparing hydrated excess proton stabilization during proton transport in M2 with the interactions revealed in the crystal structures, using the Multiscale Reactive Molecular Dynamics (MS-RMD) methodology. Along with an earlier qualitative MD simulation study that guided the design of the spiro-adamantyl amine inhibitors, 44 the crystallographic analysis provided potential insights into the mechanism of inhibition, suggesting that the backbone carbonyls of pore-lining residues act as "physiochemical chameleons", able to engage in both hydrophobic and hydrophilic interactions, and that the drug is tilted off the channel''s axis and interacts with waters in the Ala30 layer. Most recently, we further analyzed the MS-RMD simulations to explore the detailed interactions between the hydrated excess proton and the channel and found that the proton dynamically, as a function of its position, alters several properties of the protein and pore waters, including the hydrogen bonding network and the protein structure.
   abstract: [Image: see text] Prevalent resistance to inhibitors that target the influenza A M2 proton channel has necessitated a continued drug design effort, supported by a sustained study of the mechanism of channel function and inhibition. Recent high-resolution X-ray crystal structures present the first opportunity to see how the adamantyl amine class of inhibitors bind to M2 and disrupt and interact with the channel’s water network, providing insight into the critical properties that enable their effective inhibition in wild-type M2. In this work, we examine the hypothesis that these drugs act primarily as mechanism-based inhibitors by comparing hydrated excess proton stabilization during proton transport in M2 with the interactions revealed in the crystal structures, using the Multiscale Reactive Molecular Dynamics (MS-RMD) methodology. MS-RMD, unlike classical molecular dynamics, models the hydrated proton (hydronium-like cation) as a dynamic excess charge defect and allows bonds to break and form, capturing the intricate interactions between the hydrated excess proton, protein atoms, and water. Through this, we show that the ammonium group of the inhibitors is effectively positioned to take advantage of the channel’s natural ability to stabilize an excess protonic charge and act as a hydronium mimic. Additionally, we show that the channel is especially stable in the drug binding region, highlighting the importance of this property for binding the adamantane group. Finally, we characterize an additional hinge point near Val27, which dynamically responds to charge and inhibitor binding. Altogether, this work further illuminates a dynamic understanding of the mechanism of drug inhibition in M2, grounded in the fundamental properties that enable the channel to transport and stabilize excess protons, with critical implications for future drug design efforts.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32933245/
        doi: 10.1021/jacs.0c06419

         id: cord-326922-bajpr5a2
     author: Watson, C. James
      title: Pharmaceutical Compounding: a History, Regulatory Overview, and Systematic Review of Compounding Errors
       date: 2020-11-02
      words: 7095.0
  sentences: 417.0
      pages: 
     flesch: 38.0
      cache: ./cache/cord-326922-bajpr5a2.txt
        txt: ./txt/cord-326922-bajpr5a2.txt
    summary: In the modern-day United States (US), medications are by-inlarge manufactured in commercial facilities, and this production is regulated and overseen by the US Food and Drug Administration (FDA). Furthermore, a new form of large-scale compounding has become commonplace, whereby pharmacies produce bulk volumes of medications which are not available commercially, and broadly distribute them to healthcare practices and individual patients. Patient harm caused by compounded medications has been the focus of media, medical, and legislative attention in recent years, especially following a multistate, multi-fatality outbreak of fungal meningitis caused by contaminated steroid injections compounded at a pharmacy in Framingham, MA [2, 3, 5, 6] . We categorized errors under the conceptual framework described by Sarah Sellers, PharmD, MPH, former board member for the FDA''s Advisory Committee on Pharmacy Compounding, in testimony to the US Senate Committee on Health, Education, Labor, and Pensions, namely, that "suprapotency," "subpotency," and "contamination" are the primary risks associated with pharmaceutical compounding [59] .
   abstract: INTRODUCTION: Medications are compounded when a formulation of a medication is needed but not commercially available. Regulatory oversight of compounding is piecemeal and compounding errors have resulted in patient harm. We review compounding in the United States (US), including a history of compounding, a critique of current regulatory oversight, and a systematic review of compounding errors recorded in the literature. METHODS: We gathered reports of compounding errors occurring in the US from 1990 to 2020 from PubMed, Embase, several relevant conference abstracts, and the US Food and Drug Administration “Drug Alerts and Statements” repository. We categorized reports into errors of “contamination,” suprapotency,” and “subpotency.” Errors were also subdivided by whether they resulted in morbidity and mortality. We reported demographic, medication, and outcome data where available. RESULTS: We screened 2155 reports and identified 63 errors. Twenty-one of 63 were errors of concentration, harming 36 patients. Twenty-seven of 63 were contamination errors, harming 1119 patients. Fifteen errors did not result in any identified harm. DISCUSSION: Compounding errors are attributed to contamination or concentration. Concentration errors predominantly result from compounding a prescription for a single patient, and disproportionately affect children. Contamination errors largely occur during bulk distribution of compounded medications for parenteral use, and affect more patients. The burden falls on the government, pharmacy industry, and medical providers to reduce the risk of patient harm caused by compounding errors. CONCLUSION: In the US, drug compounding is important in ensuring access to vital medications, but has the potential to cause patient harm without adequate safeguards.
        url: https://www.ncbi.nlm.nih.gov/pubmed/33140232/
        doi: 10.1007/s13181-020-00814-3

         id: cord-289382-bnl9i9oy
     author: Wright, Gerard D
      title: Q&A: Antibiotic resistance: where does it come from and what can we do about it?
       date: 2010-09-20
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: nan
        url: https://doi.org/10.1186/1741-7007-8-123
        doi: 10.1186/1741-7007-8-123

         id: cord-000204-hd12p867
     author: Wu, Han-Chung
      title: Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy
       date: 2010-05-05
      words: 4433.0
  sentences: 217.0
      pages: 
     flesch: 32.0
      cache: ./cache/cord-000204-hd12p867.txt
        txt: ./txt/cord-000204-hd12p867.txt
    summary: title: Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. This article reviews the current research in developing liposomal drug delivery systems that use peptide ligands to target blood vessels in solid tumors. One peptide-conjugated liposome can deliver over ten thousand anticancer drug molecules directly into target tumor cells efficiently and effectively. In the future, combining ligands that specifically bind to cancer cells (including cancer stem cells) and tumor blood vessels with multifunctional liposomal drug delivery systems may help improve the effectiveness of cancer treatment and minimize the side effects traditionally associated with chemotherapy. The potential use of ligand-conjugated liposome-encapsulated drugs to target tumor cells and vasculature is very promising.
   abstract: Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864512/
        doi: 10.1155/2010/723798

         id: cord-267979-k70gnrdw
     author: Yıldız-Peköz, Ayca
      title: Advances in Pulmonary Drug Delivery
       date: 2020-09-23
      words: 3257.0
  sentences: 159.0
      pages: 
     flesch: 38.0
      cache: ./cache/cord-267979-k70gnrdw.txt
        txt: ./txt/cord-267979-k70gnrdw.txt
    summary: This Special Issue brings together recent advances in the areas of inhalation device testing, aerosol formulation development, use of in vitro and in silico models in pulmonary drug deposition and drug disposition studies, and pulmonary delivery of complex drugs, such as vaccines, antibiotics and peptides, to or via the lungs. The development of modern-day inhalers, e.g., pressurised metered-dose inhalers (pMDIs) and more recently, dry powder inhalers (DPIs), jet and vibrating mesh nebulisers (VMNs), and soft mist inhalers (SMIs), has given pulmonary drug delivery a momentum boost that transformed a therapeutic niche into a market predicted to hit US$41.5 billion by 2026 [1] . Development of an innovative, carrier-based dry powder inhalation formulation containing spray-dried meloxicam potassium to improve the in vitro and in silico aerodynamic properties Excipient interactions in glucagon dry powder inhaler formulation for pulmonary delivery Inhalable dry powder of bedaquiline for pulmonary tuberculosis: In vitro physicochemical characterization, antimicrobial activity and safety studies
   abstract: Pulmonary drug delivery represents an attractive, non-invasive administration option. In addition to locally acting drugs, molecules that are intended to produce systemic effects can be delivered via the pulmonary route. Several factors need to be considered in the context of delivering drugs to or via the lungs—in addition to the drug itself, its formulation into an appropriate inhalable dosage form of sufficient stability is critical. It is also essential that this formulation is paired with a suitable inhaler device, which generates an aerosol of a particle/droplet size that ensures deposition in the desired region of the respiratory tract. Lastly, the patient’s (patho-) physiology and inhalation manoeuvre are of importance. This Special Issue brings together recent advances in the areas of inhalation device testing, aerosol formulation development, use of in vitro and in silico models in pulmonary drug deposition and drug disposition studies, and pulmonary delivery of complex drugs, such as vaccines, antibiotics and peptides, to or via the lungs.
        url: https://doi.org/10.3390/pharmaceutics12100911
        doi: 10.3390/pharmaceutics12100911

         id: cord-313268-j51zyodw
     author: Zeng, Xiangxiang
      title: Repurpose Open Data to Discover Therapeutics for COVID-19 Using Deep Learning
       date: 2020-07-12
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: [Image: see text] There have been more than 2.2 million confirmed cases and over 120 000 deaths from the human coronavirus disease 2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), in the United States alone. However, there is currently a lack of proven effective medications against COVID-19. Drug repurposing offers a promising route for the development of prevention and treatment strategies for COVID-19. This study reports an integrative, network-based deep-learning methodology to identify repurposable drugs for COVID-19 (termed CoV-KGE). Specifically, we built a comprehensive knowledge graph that includes 15 million edges across 39 types of relationships connecting drugs, diseases, proteins/genes, pathways, and expression from a large scientific corpus of 24 million PubMed publications. Using Amazon’s AWS computing resources and a network-based, deep-learning framework, we identified 41 repurposable drugs (including dexamethasone, indomethacin, niclosamide, and toremifene) whose therapeutic associations with COVID-19 were validated by transcriptomic and proteomics data in SARS-CoV-2-infected human cells and data from ongoing clinical trials. Whereas this study by no means recommends specific drugs, it demonstrates a powerful deep-learning methodology to prioritize existing drugs for further investigation, which holds the potential to accelerate therapeutic development for COVID-19.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32654489/
        doi: 10.1021/acs.jproteome.0c00316

         id: cord-178783-894gkrsk
     author: Zhang, Rui
      title: Drug Repurposing for COVID-19 via Knowledge Graph Completion
       date: 2020-10-19
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Objective: To discover candidate drugs to repurpose for COVID-19 using literature-derived knowledge and knowledge graph completion methods. Methods: We propose a novel, integrative, and neural network-based literature-based discovery (LBD) approach to identify drug candidates from both PubMed and COVID-19-focused research literature. Our approach relies on semantic triples extracted using SemRep (via SemMedDB). We identified an informative subset of semantic triples using filtering rules and an accuracy classifier developed on a BERT variant, and used this subset to construct a knowledge graph. Five SOTA, neural knowledge graph completion algorithms were used to predict drug repurposing candidates. The models were trained and assessed using a time slicing approach and the predicted drugs were compared with a list of drugs reported in the literature and evaluated in clinical trials. These models were complemented by a discovery pattern-based approach. Results: Accuracy classifier based on PubMedBERT achieved the best performance (F1= 0.854) in classifying semantic predications. Among five knowledge graph completion models, TransE outperformed others (MR = 0.923, Hits@1=0.417). Some known drugs linked to COVID-19 in the literature were identified, as well as some candidate drugs that have not yet been studied. Discovery patterns enabled generation of plausible hypotheses regarding the relationships between the candidate drugs and COVID-19. Among them, five highly ranked and novel drugs (paclitaxel, SB 203580, alpha 2-antiplasmin, pyrrolidine dithiocarbamate, and butylated hydroxytoluene) with their mechanistic explanations were further discussed. Conclusion: We show that an LBD approach can be feasible for discovering drug candidates for COVID-19, and for generating mechanistic explanations. Our approach can be generalized to other diseases as well as to other clinical questions.
        url: https://arxiv.org/pdf/2010.09600v1.pdf
        doi: nan

         id: cord-317435-4yuw7jo3
     author: Zhou, Yadi
      title: Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2
       date: 2020-03-16
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
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    summary: 
   abstract: Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV/SARS-CoV-2. Drug repurposing, representing as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV–host interactome and drug targets in the human protein–protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV/SARS-CoV-2 shares the highest nucleotide sequence identity with SARS-CoV (79.7%). Specifically, the envelope and nucleocapsid proteins of 2019-nCoV/SARS-CoV-2 are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and HCoV–host interactions in the human interactome, we prioritize 16 potential anti-HCoV repurposable drugs (e.g., melatonin, mercaptopurine, and sirolimus) that are further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. We further identify three potential drug combinations (e.g., sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the “Complementary Exposure” pattern: the targets of the drugs both hit the HCoV–host subnetwork, but target separate neighborhoods in the human interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations targeting 2019-nCoV/SARS-CoV-2.
        url: https://www.ncbi.nlm.nih.gov/pubmed/32194980/
        doi: 10.1038/s41421-020-0153-3

         id: cord-353572-b4mdiont
     author: Zhou, Yadi
      title: Network-based Drug Repurposing for Human Coronavirus
       date: 2020-02-05
      words: 6871.0
  sentences: 390.0
      pages: 
     flesch: 42.0
      cache: ./cache/cord-353572-b4mdiont.txt
        txt: ./txt/cord-353572-b4mdiont.txt
    summary: Using network proximity analyses of drug targets and known HCoV-host interactions in the human protein-protein interactome, we computationally identified 135 putative repurposable drugs for the potential prevention and treatment of HCoVs. In addition, we prioritized 16 potential anti-HCoV repurposable drugs (including melatonin, mercaptopurine, and sirolimus) that were further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations toward future clinical trials for HCoVs. Coronaviruses (CoVs) typically affect the respiratory tract of mammals, including humans, and lead to mild to severe respiratory tract infections [1] . These network proximity analyses offer putative repurposable candidates for potential prevention and treatment of HCoVs. To further validate the 135 repurposable drugs against HCoVs, we first performed gene set enrichment analysis (GSEA) using transcriptome data of MERS-CoV and SARS-CoV infected host cells (see Methods).
   abstract: Human Coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle east respiratory syndrome coronavirus (MERS-CoV), and 2019 novel coronavirus (2019-nCoV), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV. Drug repurposing, represented as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV has the highest nucleotide sequence identity with SARS-CoV (79.7%) among the six other known pathogenic HCoVs. Specifically, the envelope and nucleocapsid proteins of 2019-nCoV are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and known HCoV-host interactions in the human protein-protein interactome, we computationally identified 135 putative repurposable drugs for the potential prevention and treatment of HCoVs. In addition, we prioritized 16 potential anti-HCoV repurposable drugs (including melatonin, mercaptopurine, and sirolimus) that were further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. Finally, we showcased three potential drug combinations (including sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the Complementary Exposure pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human protein-protein interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations toward future clinical trials for HCoVs.
        url: https://doi.org/10.1101/2020.02.03.20020263
        doi: 10.1101/2020.02.03.20020263

         id: cord-284208-8fsqgkw5
     author: Zolla, Lello
      title: Proteomics studies reveal important information on small molecule therapeutics: a case study on plasma proteins
       date: 2008-11-07
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: The most abundant proteins in serum, such as albumin and IgG, act as molecular sponges that bind and transport low molecular weight proteins/peptides and drugs. In the near future, pharmacoproteomics, the use of proteomic technologies in the field of drug discovery and development, and interactomics, the branch of proteomics which is concerned with identifying interactions between proteins, will allow researchers to (i) know the specific protein changes that occur in biological compartments in response to drug administration; (ii) design small novel therapeutic molecules that can have extended half-lives if carried by plasma protein in the blood stream. Advances in these fields will open new avenues of tailor-made molecular therapy, reducing present limitations on treatment arising from toxicity and inefficiency. In this short review we report and discuss the most recent developments arising from the use of proteomic tools in blood plasma protein research, looking at the identification of proteins found in plasma as well as their interactions with small molecules such as drugs, peptides, organic chemicals and metals. We believe this research demonstrates that proteomic technologies, and in particular pharmacoproteomics, interactomics and post-translational modification analysis, could be instrumental in the design of new tailor-made drugs leading to substantial improvements in molecular therapy.
        url: https://doi.org/10.1016/j.drudis.2008.09.013
        doi: 10.1016/j.drudis.2008.09.013

         id: cord-002774-tpqsjjet
     author: nan
      title: Section II: Poster Sessions
       date: 2017-12-01
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711696/
        doi: 10.1093/jurban/jti137

         id: cord-006226-fn7zlutj
     author: nan
      title: Abstracts of the 4th annual meeting of the German Society of Clinical Pharmacology and Therapy: Hannover, 14–17 September 1994
       date: 1994
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100636/
        doi: 10.1007/bf00193489

         id: cord-006229-7yoilsho
     author: nan
      title: Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH)
       date: 2016-02-06
      words: 133493.0
  sentences: 6804.0
      pages: 
     flesch: 42.0
      cache: ./cache/cord-006229-7yoilsho.txt
        txt: ./txt/cord-006229-7yoilsho.txt
    summary: It directly activates Protein Kinase A (PKA) or the Exchange protein directly activated by cAMP (Epac) which is a guanine exchange factor (GEF) for the small monomeric GTPase Rap. As Human umbilical vein endothelial cells (HUVEC) express both cAMP effectors (Epac1 and PKA), we investigated the role of cAMP-signaling using a spheroid based sprouting assay as an in vitro model for angiogenesis. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration Methods and Results: Here we demonstrate that dexamethasone treatment lowered S1P 1 mRNA and protein expression levels in rat mesangial cells measured by TaqMan® and Western blot analyses. The aim of this study was to investigate the relevance of IGFBP5 in cardiogenesis and cardiac remodeling and its role as a potential target for ameliorating stress-induced cardiac remodeling Methods and Results: We investigated the expression of Igfbp5 in murine cardiac tissue at different developmental stages by qPCR normalized to Tpt1 (Tumor Protein, Translationally-Controlled 1).
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100641/
        doi: 10.1007/s00210-016-1213-y

         id: cord-014687-0am4l5ms
     author: nan
      title: SPR 2012
       date: 2012-03-29
      words: 98592.0
  sentences: 5600.0
      pages: 
     flesch: 43.0
      cache: ./cache/cord-014687-0am4l5ms.txt
        txt: ./txt/cord-014687-0am4l5ms.txt
    summary: This presentation will focus on recent developments that have lead to a better understanding of the embryopathogenesis for fibropolycystic liver diseases (including choledochal cysts and Caroli disease), histopathological findings that have led to new classification systems for of pediatric vascular anomalies, technological advances and contrast agents in magnetic resonance imaging that are useful to characterize and limit the differential diagnosis of hepatic masses. Disclosure: Dr. Annapragada has indicated that he is a stock holder and consultant for Marval Biosciences Inc. Paper #: PA-067 Cardiovascular Image Quality Using a Nanoparticle CT Contrast Agent: Preliminary Studies in a Pig Model Rajesh Krishnamurthy, Radiology, Texas Children''s Hospital, rxkrishn@texaschildrens.org; Ketan Ghaghada, Prakash Masand, Abhay Divekar, Eric Hoffman, Ananth Annapragada Purpose or Case Report: Image quality in a separate study using a long circulating, liposomal-based nanoscale blood pool iodinated contrast agent (NCTX) suggests clinical utility in pediatrics, potentially reducing difficulties in contrast-CT of children with congenital heart disease (CHD) including the size of intravenous cannula, need for accurate timing, inability to simultaneously opacify multiple targets of interest (requiring repeated contrast administration and/or repeated imaging).
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080092/
        doi: 10.1007/s00247-012-2356-8

         id: cord-014875-xhzxhwgo
     author: nan
      title: Book Reviews
       date: 2003
      words: 7144.0
  sentences: 338.0
      pages: 
     flesch: 46.0
      cache: ./cache/cord-014875-xhzxhwgo.txt
        txt: ./txt/cord-014875-xhzxhwgo.txt
    summary: The last chapter in the second focused area is by Pumpens and Grens, who provide an in-depth discussion of the use of viral vectors for delivering a desirable gene into target cells for protein production. The chapters don''t cover material in great depth (and if they did, this book will be many times larger) but they provide enough information to cover what someone new to the area would need to know to get started. As described above, this book does not intend to summarize transporters related to drugs rather tried to introduce many technologies to be used in future studies for molecular cloning, structure, functionality, regulation, and sorting in various point of views by using typical experimental results on physiologically important transporter molecules. Each chapter provides a polymer-based step-bystep description of not only basic information including various classification, application, and structure-property relationships, but also very practical descriptions of synthetic and analytic techniques that are believed to be good references in research laboratories.
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089263/
        doi: 10.1023/b:pham.0000008097.92834.f4

         id: cord-015334-8p124rwp
     author: nan
      title: ESCP 36th European Symposium on Clinical Pharmacy ‘Implementing Clinical Pharmacy in Community and Hospital Settings: Sharing the Experience’, Istanbul, Turkey 25–27 October 2007; Abstracts
       date: 2008-06-11
      words: 51143.0
  sentences: 3291.0
      pages: 
     flesch: 51.0
      cache: ./cache/cord-015334-8p124rwp.txt
        txt: ./txt/cord-015334-8p124rwp.txt
    summary: Based on the results of the pharmacoeconomic analysis, development of clinical pharmacy and CIVAS for some drugs will be discussed with the paediatric department Background and Objective: Studies show that up to 38% of patients starting treatment with antidepressants fill only a single prescription at the pharmacy, apparently not accepting treatment. Main Outcome Measures: Data collected were: nurses'' profile (age, length of service, competencies'' self-assessment), knowledge on drugs prescribed to their patients (usage, administration, side-effects, drug interactions…), use of existing tools (i.e. drugs database) and possible tools to be developed by the pharmacy ward to help them in their daily practice. The objectives were:(1)To identify the most relevant minor ailments, agreeing on the specific criteria for referral to the GP.(2)To select the non-prescription drugs, with evidence of safety and effectiveness, for the treatment of the identified minor ailments Design: Qualitative study with an expert panel which was made up of 2 primary care physician from SEMFYC and six community pharmacists (two members of SEFAC and four members of GIAF-UGR).
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102062/
        doi: 10.1007/s11096-008-9226-3

         id: cord-024833-e6vcf4un
     author: nan
      title: Forum
       date: 2019-12-19
      words: 8110.0
  sentences: 391.0
      pages: 
     flesch: 48.0
      cache: ./cache/cord-024833-e6vcf4un.txt
        txt: ./txt/cord-024833-e6vcf4un.txt
    summary: Approximately 80% of US hospitals rely on data and recommendations from the ECRI Institute to protect patients from unsafe practices and ineffective products, while the ISMP''s efforts to improve safety in patients have resulted in changes to clinical practice and public policy, including improvements in drug labelling, packaging, preparation and administration. The FDA has now announced the availability of a draft document entitled "Best Practices in Drug and Biological Product Postmarket Safety Surveillance for FDA Staff", which outlines the agency''s approach to timely postmarketing analyses of drugs and biologics, and "includes a high-level overview of tools, methods, and signal detection and evaluation activities, using varied data sources, for drug safety surveillance to provide a broader context and a general overview of our overarching effort and commitment in this area", says Woodcock. Analysis of spontaneous ADR reports to the European Medicine Agency''s EudraVigilance database has identified new safety signals for asthma drugs in paediatric patients, say authors of a study published in Drug Safety.
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223806/
        doi: 10.1007/s40290-019-00321-z

         id: cord-265848-afkeuwup
     author: nan
      title: Chapter 2 Emergency Management of Poisoning
       date: 2007-12-31
      words: 27412.0
  sentences: 1589.0
      pages: 
     flesch: 39.0
      cache: ./cache/cord-265848-afkeuwup.txt
        txt: ./txt/cord-265848-afkeuwup.txt
    summary: With the use of drugs having a short duration of action, RSI also is advantageous because it is a measure that permits temporary airway control for the patient with mildly compromised airway reflexes who requires gastrointestinal decontamination (lavage followed by activated charcoal administration) but who does not require prolonged intubation. The management of gastrointestinal disturbance in the toxic patient includes following the general principles of blood, fluid, and electrolyte resuscitation, when indicated; judicious use of parenteral antiemetics to control persistent vomiting; specific measures such as antidotal therapy (e.g., in iron or organophosphate poisoning); or interventional therapy, such as charcoal hemoperfusion (in theophylline overdose) or hemodialysis (in lithium overdose), when indicated.
   abstract: nan
        url: https://api.elsevier.com/content/article/pii/B9780721606934500074
        doi: 10.1016/b978-0-7216-0693-4.50007-4

         id: cord-350571-6tapkjb6
     author: nan
      title: 45th ESCP-NSF international symposium on clinical pharmacy: clinical pharmacy tackling inequalities and access to health care. Oslo, Norway, 5–7 October 2016
       date: 2017-01-10
      words: 106013.0
  sentences: 6203.0
      pages: 
     flesch: 48.0
      cache: ./cache/cord-350571-6tapkjb6.txt
        txt: ./txt/cord-350571-6tapkjb6.txt
    summary: Possible solutions might be to use shared communication tools like Internet based communication programs and to introduce the patient as a participant at the IMRs. Please specify your abstract type: Research abstract Background and objective: International good pharmacy practice guidelines describe how pharmacists should counsel the patients about their medicines, offer additional services where needed, and intervene at drug related problems. Please specify your abstract type: Descriptive abstract (for projects) Background and objective: In order to improve the medication reconciliation and to implement training programs for the medical team in an associated to general hospital nursing (ASNH) home we measured the discrepancies between pharmacy registered treatments (PRT) and medical prescriptions (MP), and we analysed potentially inappropriate prescriptions according to ''''American Geriatrics Society 2015 Beers Criteria'''' and ''''STOPP-START 2014 criteria.
   abstract: nan
        url: https://www.ncbi.nlm.nih.gov/pubmed/28074393/
        doi: 10.1007/s11096-016-0404-4

         id: cord-350703-vrqltz3s
     author: nan
      title: ISAR News
       date: 2016-01-31
      words: nan
  sentences: nan
      pages: 
     flesch: nan
      cache: 
        txt: 
    summary: 
   abstract: nan
        url: https://api.elsevier.com/content/article/pii/S0166354215002867
        doi: 10.1016/s0166-3542(15)00286-7

         id: cord-289321-ahl46ql9
     author: van Buuren, Nicholas
      title: Transmission genetics of drug-resistant hepatitis C virus
       date: 2018-03-28
      words: 7817.0
  sentences: 394.0
      pages: 
     flesch: 48.0
      cache: ./cache/cord-289321-ahl46ql9.txt
        txt: ./txt/cord-289321-ahl46ql9.txt
    summary: Differential visualization of drug-resistant and -susceptible RNA genomes within cells revealed that resistant variants of NS3/4A protease and NS5A phosphoprotein are cis-dominant, ensuring their direct selection from complex environments. Our goal was to screen the HCV-encoded viral proteins that are current targets of antiviral compounds to determine the intracellular dominance relationships between drug-resistant and drug-susceptible genomes. To test whether susceptibility to NS5A inhibitors was dominant in the context of viral infections, we analyzed U, S, S + R and R cell populations by flow cytometry as previously performed for the NS3/4A inhibitor in Figure 3 . To test whether exogenously expressed drug-susceptible NS5A proteins could co-assemble with drug-resistant NS5A, we utilized the previously described HCV plasmid that expresses HA-tagged and GFP-tagged NS5A within the same polyprotein but does not support genome replication ( Figure 5A) . Failure of NS5A proteins to mix during infection is a likely explanation for the cis-dominance of drug resistance observed in cultured cells (Figure 4) .
   abstract: Antiviral development is plagued by drug resistance and genetic barriers to resistance are needed. For HIV and hepatitis C virus (HCV), combination therapy has proved life-saving. The targets of direct-acting antivirals for HCV infection are NS3/4A protease, NS5A phosphoprotein and NS5B polymerase. Differential visualization of drug-resistant and -susceptible RNA genomes within cells revealed that resistant variants of NS3/4A protease and NS5A phosphoprotein are cis-dominant, ensuring their direct selection from complex environments. Confocal microscopy revealed that RNA replication complexes are genome-specific, rationalizing the non-interaction of wild-type and variant products. No HCV antivirals yet display the dominance of drug susceptibility shown for capsid proteins of other viruses. However, effective inhibitors of HCV polymerase exact such high fitness costs for drug resistance that stable genome selection is not observed. Barriers to drug resistance vary with target biochemistry and detailed analysis of these barriers should lead to the use of fewer drugs.
        url: https://www.ncbi.nlm.nih.gov/pubmed/29589830/
        doi: 10.7554/elife.32579

==== make-pages.sh questions [ERIC WAS HERE]
==== make-pages.sh search
/data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory
Traceback (most recent call last):
  File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in <module>
    with open( TEMPLATE, 'r' ) as handle : htm = handle.read()
FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm'
==== make-pages.sh topic modeling corpus
Zipping study carrel