Relevant bibliographies by topics / Drug screening model

Academic literature on the topic 'Drug screening model'

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Published: 10 December 2022
Last updated: 28 January 2023

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Journal articles on the topic "Drug screening model"

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ANENE-NZELU, CHUKWUEMEKA, YAN WANG, HANRY YU, and LEO HWA LIANG. "LIVER TISSUE MODEL FOR DRUG TOXICITY SCREENING." Journal of Mechanics in Medicine and Biology 11, no. 02 (April 2011): 369–90. http://dx.doi.org/10.1142/s0219519411004083.

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Understanding the mechanisms involved in the biotransformation of new drugs and their toxicological implications is important for drug development. In this regard, a lot of effort has been put into research to recreate the liver tissue in the laboratory for the purpose of drug screening. This has also helped to minimize the use of laboratory animal and reduce incidence of post-market withdrawal of drugs. Despite the progress made so far, cell source remains a major limitation since primary human hepatocytes are scarce and the various cell alternatives do not express all the genes found in the normal liver. In terms of tissue construct, there is a current shift to 3D models since the cell–cell interactions found in the 3D configuration enhance the morphology and function of hepatocytes. Furthermore, the engineered tissue's performance can be optimized by cocultures, perfusion-based systems, and the use of scaffolds. Nanotechnology seems promising in the field of tissue engineering, as it has been proven that cell–matrix interactions at the nano level can influence greatly on the outcome of the tissue. The review explores the various cell sources, the 3D model, flow-based systems, cocultures, and nanoscaffolds use in hepatocytes in vitro drug testing
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Genri, Kawahara, and Yukiko Hayashi. "Drug screening using transgenic zebrafish model." Proceedings for Annual Meeting of The Japanese Pharmacological Society 94 (2021): 2—S17–3. http://dx.doi.org/10.1254/jpssuppl.94.0_2-s17-3.

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Liang, Qiying, Peng Ma, Qi Zhang, Youjie Yin, Ping Wang, Saifei Wang, Yao Zhang, Ruolei Han, and Hansong Deng. "A gum Arabic assisted sustainable drug delivery system for adult Drosophila." Biology Open 9, no. 6 (June 2, 2020): bio052241. http://dx.doi.org/10.1242/bio.052241.

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ABSTRACTLarge-scale compound screening in adult flies is hampered by the lack of continuous drug delivery systems and poor solubility of numerous compounds. Here we found that gum Arabic (Acacia/Senegal gum), a widely used stabilizer, can also emulsify lipophilic compounds and profoundly increase their accessibility to target tissues in Drosophila and mice. We further developed a gum Arabic-based drug delivery system, wherein the drug was ground into gum Arabic and emulsified in liquid food fed to flies by siphoning through a U-shape glass capillary. This system did not affect food intake nor cell viability. Since drugs were continuously delivered by siphoning, minimal compound waste and less frequent food changes make this system ideal for large-scale long-term screenings. In our pilot screening for antitumor drugs in the NCI DTP library, we used a Drosophila model of colorectal cancer and identified two drugs that are especially hydrophobic and were not identified in previous screenings. Our data demonstrated that gum Arabic facilitates drug delivery in animal models and the system is suitable for long-term high-throughput drug screening in Drosophila. This system would accelerate drug discovery for chronic and cognitive conditions.
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Kondo, Jumpei, and Masahiro Inoue. "Application of Cancer Organoid Model for Drug Screening and Personalized Therapy." Cells 8, no. 5 (May 17, 2019): 470. http://dx.doi.org/10.3390/cells8050470.

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Drug screening—i.e., testing the effects of a number of drugs in multiple cell lines—is used for drug discovery and development, and can also be performed to evaluate the heterogeneity of a disease entity. Notably, intertumoral heterogeneity is a large hurdle to overcome for establishing standard cancer treatment, necessitating disease models better than conventional established 2D cell lines for screening novel treatment candidates. In the present review, we outline recent progress regarding experimental cancer models having more physiological and clinical relevance for drug screening, which are important for the successful evaluation of cellular response to drugs. The review is particularly focused on drug screening using the cancer organoid model, which is emerging as a better physiological disease model than conventional established 2D cell lines. We also review the use of cancer organoids to examine intertumor and intratumor heterogeneity, and introduce the perspective of the clinical use of cancer organoids to enable precision medicine.
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Cagan, Ross. "Drug screening using model systems: some basics." Disease Models & Mechanisms 9, no. 11 (November 1, 2016): 1241–44. http://dx.doi.org/10.1242/dmm.028159.

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Liu, Chen, Tianyu Qin, Yuhan Huang, Yuan Li, Gang Chen, and Chaoyang Sun. "Drug screening model meets cancer organoid technology." Translational Oncology 13, no. 11 (November 2020): 100840. http://dx.doi.org/10.1016/j.tranon.2020.100840.

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Parng, Chuenlei, Wen Lin Seng, Carlos Semino, and Patricia McGrath. "Zebrafish: A Preclinical Model for Drug Screening." ASSAY and Drug Development Technologies 1, no. 1 (November 2002): 41–48. http://dx.doi.org/10.1089/154065802761001293.

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Callahan, H. L., A. C. Portal, R. Devereaux, and M. Grogl. "An axenic amastigote system for drug screening." Antimicrobial Agents and Chemotherapy 41, no. 4 (April 1997): 818–22. http://dx.doi.org/10.1128/aac.41.4.818.

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Currently available primary screens for selection of candidate antileishmanial compounds are not ideal. The choices include screens that are designed to closely reflect the situation in vivo but are labor-intensive and expensive (intracellular amastigotes and animal models) and screens that are designed to facilitate rapid testing of a large number of drugs but do not use the clinically relevant parasite stage (promastigote model). The advent of successful in vitro culture of axenic amastigotes permits the development of a primary screen which is quick and easy like the promastigote screen but still representative of the situation in vivo, since it uses the relevant parasite stage. We have established an axenic amastigote drug screening system using a Leishmania mexicana strain (strain M379). A comparison of the 50% inhibitory concentration (IC50) drug sensitivity profiles of M379 promastigotes, intracellular amastigotes, and axenic amastigotes for six clinically relevant antileishmanial drugs (sodium stibogluconate, meglumine antimoniate, pentamidine, paromomycin, amphotericin B, WR6026) showed that M379 axenic amastigotes are a good model for a primary drug screen. Promastigote and intracellular amastigote IC50s differed for four of the six drugs tested by threefold or more; axenic amastigote and intracellular amastigote IC50s differed by twofold for only one drug. This shows that the axenic amastigote susceptibility to clinically used reference drugs is comparable to the susceptibility of amastigotes in macrophages. These data also suggest that for the compounds tested, susceptibility is intrinsic to the parasite stage. This contradicts previous hypotheses that suggested that the activities of antimonial agents against intracellular amastigotes were solely a function of the macrophage.
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Dixit, Vaibhav A. "A simple model to solve a complex drug toxicity problem." Toxicology Research 8, no. 2 (2019): 157–71. http://dx.doi.org/10.1039/c8tx00261d.

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Decker, S., M. Hollingshead, C. A. Bonomi, J. P. Carter, and E. A. Sausville. "The hollow fibre model in cancer drug screening." European Journal of Cancer 40, no. 6 (April 2004): 821–26. http://dx.doi.org/10.1016/j.ejca.2003.11.029.

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Dissertations / Theses on the topic "Drug screening model"

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Psaroudakis, G. "Virtual screening in drug design and model evaluation." Thesis, University of Essex, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.422234.

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Wu, Yuelong Ph D. Massachusetts Institute of Technology. "A high-throughput antiepileptic drug screening system based on chemically Induced zebrafish behavioral model." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/93816.

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Thesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2014.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 53-59).
Epilepsy, which has the largest worldwide impacts among all nervous system diseases expect for stroke and dementia, is a group of long-term neurological disorders characterized by epileptic seizures. AED medications are the mainstay for epileptic seizure management. However, the existing AEDs cannot fit the needs for every patient due to the efficacy and side effect issues. In this thesis, a high-throughput system to screen new antiepileptic drug is built up. Chemically induced zebrafish larvae are used as a seizure model. The change in fishes' behavior patterns serves as an indicator of the fishes' nervous system condition. The design of the behavior data acquisition setup as well as the requirements of its components is described. A fish tracking program that tracks the locomotion variables like the head position, the tail movement and sideway orientation etc. is developed. The tracking results are treated either by simply computing the statistics of the tracking variables or implementing behavior pattern classifications. Two test datasets involving two different convulsants and one known AED are acquired and analyzed. The results coincide with the existing knowledge about the chemicals' effects on the human nerve system, which suggests the system described in this thesis is promising to help with the actual AED development.
by Yuelong Wu.
S.M.
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Wu, Calvin. "In Vitro Cortical Networks for Disease Modeling and Drug Evaluation." Thesis, University of North Texas, 2013. https://digital.library.unt.edu/ark:/67531/metadc407860/.

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In translational research, disease models in preclinical studies are used as media for discovery of drugs or novel therapeutics. Development of in vitro models for various neurological diseases that enable efficient pharmacological or toxicological screening has been ongoing but challenging. Recognizing the potential benefit of in vitro disease models, dysfunctions in the cortical neuronal networks were induced to mimic the functional pathology of neurological symptoms using microelectrode arrays. Two different disease states – tinnitusand excitotoxicity – were investigated and discussed. In this model, pentylenetetrazol-induced increase in spontaneous firing rate and synchrony in the auditory cortical networks was used as correlate of tinnitus. Potential tinnitus treatment drugs from several different classes – including the novel class of potassium channel openers – were screened and quantified. The potentialtherapeutic values of these drugs were also discussed as the basis for drug repurposing. Functional excitotoxicity was induced by cisplatin (a cancer drug that causes neurological sideeffects) and glutamate (the major excitatory neurotransmitter). As proof-of-principle that the model may contribute to expediting the development of therapeutics, cisplatin excitotoxicity wasprevented by the antioxidant D-methionine, while glutamate excitotoxicity was prevented by ceftriaxone (a modulator of a glutamate reuptake transporter). In the latter part of the study, with results linking two of the screened drugs L-carnitine and D-methionine to GABAA receptor activation, it was demonstrated that this model not only served as an efficient drug-screening platform, but can be utilized to functionally investigate the underlying mechanism of drugs. Inaddition, several practical or conceptual directions for future studies to improve on this in vitro disease model are suggested.
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Aldhumani, Ali Hamed. "Pharmacophore Model Development: Targeting Noncoding RNA for Antibacterial/Antiviral Drug Discovery." Ohio University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1610705872573225.

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Guzman, Castro Gustavo Adolfo [Verfasser], and Stephan [Akademischer Betreuer] Reichl. "Human Hemicornea Model for Drug Transport Testing and Screening of Excipients / Gustavo Adolfo Guzman Castro ; Betreuer: Stephan Reichl." Braunschweig : Technische Universität Braunschweig, 2017. http://d-nb.info/1175816949/34.

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Zraikat, Manar Saleh Ali. "Development of in vitro models of invasion for the pharmacological investigation of small molecule inhibitors of tumour progression : development and validation of a 3-dimensional tumour spheroid invasion model to evaluate the pharmacological effects of novel small molecule β3 integrin antagonists." Thesis, University of Bradford, 2015. http://hdl.handle.net/10454/7511.

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Tumour dissemination is a major reason for failure of therapy for many tumour types therefore there is a requirement for novel targets & therapies. The αIIbβ3 and αvβ3 integrins have been demonstrated to have significant involvement at many stages of the tumour dissemination process including, tumour cell adhesion, migration, metastasis and angiogenesis, and thus the β3 integrins are a potential target for therapeutic antagonism with small molecules. Because of the clear interaction between the different integrin types, targeting integrins as a therapeutic strategy requires targeting more than one integrin type. Consequently, the ICT is developing a group of novel new αIIbβ3 and αvβ3 integrin dual antagonists. One of the main challenges is having a relevant, validated experimental model that expresses these integrins. The aim of the work presented here is to develop and validate an in vitro αIIbβ3 and αvβ3 integrin expressing assay of tumour cell invasion. The spheroid invasion assay has the advantage over standard monolayer transwell chamber invasion assays of being a 3-dimensional assay, and thus mimics better the cell-cell interactions and architecture that are present in a tumour compared to the monolayer-based assay. A panel of human cancer cell lines known to express one of the molecular targets of interest, αvβ3 integrin was evaluated for the ability to form spheroids and to invade through collagen matrices. One glioma cell line, U87-MG, demonstrated consistent spheroid formation and invasion and was thus selected for further studies. Optimum conditions were established for use of U87-MG in the invasion assay, and the assay was validated using a known inhibitor of invasion, LiCl and known β3 antagonist, cRGDfV. Subsequently a group of novel small molecule β3 antagonists were evaluated at nontoxic concentrations using the assay. Both LiCl and cRGDfV inhibited spheroid invasion through the gel in a dose-dependent manner, thus validating the assay. Furthermore, when the novel small molecule β3 antagonists were evaluated using the model, a dose and time dependent reduction in U87-MG spheroids invasion in collagen was observed. In further work initial steps were taken to construct a cell line which expresses both αIIbβ3 and αvβ3 integrin to use in the model to assess for dual integrin antagonism. In conclusion, this work has established a validated assay which has been utilised for some compounds to evaluate a group of novel small molecule β3 integrin antagonists with encouraging results.
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Lee, Bill. "Preclinical antimicrobial drug discovery : development and evaluation of a platform for high-throughput screening in vitro and an immunocompromised animal model." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=100745.

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The incidence of infections caused by antibiotic-resistant bacteria and fungi is rising rapidly. Once considered as little more than a nuisance, antibiotic resistance has become a serious threat. The mortality rate for some infections is approaching that of the pre-antibiotic era. New antimicrobials are needed urgently. Prior to the introduction of any new antimicrobial, comprehensive toxicity and efficacy profiles are assessed in preclinical studies. This thesis focuses on two key stages of preclinical antimicrobial drug development, specifically compound screening in vitro and animal efficacy testing in vivo. We developed a sensitive colorimetric platform with high-throughput capacity for the rapid screening of candidate antimicrobials. This platform could be adapted to assess compounds targeting a range of bacteria, fungi (such as Candida albicans), and protozoan parasites (such as Leishmania major). When this assay was modified to measure minimum inhibitory concentrations (MICs) for bacteria, 100% agreement within one dilution was achieved compared to the gold-standard method. A novel antifungal compound was taken forward to animal testing in an immunocompromised mouse model. We demonstrated herein that a histone deacetylase inhibitor in combination with an imidazole can synergise to produce a potent antifungal effect. A dose-dependent response, defined as a lower fungal burden and a higher survival rate, was achieved with increasing concentrations of the novel inhibitor.
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Robinson, Clayt Austin. "Development of an in vitro three-dimensional model for colon cancer study and drug efficacy analysis." Connect to resource, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1124223577.

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Thesis (Ph. D.)--Ohio State University, 2005.
Title from first page of PDF file. Document formatted into pages; contains xvi, 204 p.; also includes graphics (some col.). Includes bibliographical references (p. 196-204). Available online via OhioLINK's ETD Center
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Lindquist, Tera M. "The development of zebrafish (Danio rerio) as a rapid and efficient model system for therapeutic drug screening for Spinal Muscular Atrophy." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1311694979.

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Mosaad, Eman Mohamed Othman. "Three dimensional prostate cancer model systems." Thesis, Queensland University of Technology, 2018. https://eprints.qut.edu.au/118287/1/Eman%20Mohamed%20Othman_Mosaad_Thesis.pdf.

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The prediction of drug efficacy is a major limitation in the cancer research field. This thesis was a step forward in developing an in vitro 3-dimensional prostate cancer model as a potential high throughput drug-screening platform. The merits of using a high throughput microwell platform to efficiently manufacture hundreds of multicellular spheroids were evaluated. The improved Microwell-mesh platform was evaluated as a drug-screening platform. A critical factor was the discovery of the cell-specific bioluminescence assay instability, which was promoter and/or cell line dependent. The first multicellular co-culture micro-tumour system as a potential drug-screening platform for bone metastatic prostate cancer was developed.
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Books on the topic "Drug screening model"

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Ramachandran, Saravanan, and Senthilkumar Rajagopal. Zebrafish: A Model for Marine Peptide Based Drug Screening. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-7844-7.

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Mylonakis, Eleftherios, and George Tegos. Antimicrobial drug discovery: Emerging strategies. Wallingford, Oxfordshire: CABI, 2012.

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Eugene, Lloyd W., American Academy of Veterinary and Comparative Toxicology., and Iowa State University. Veterinary Diagnostic Laboratory., eds. Safety evaluation of drugs and chemicals. Washington: Hemisphere Pub. Corp., 1986.

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Seminar on Human Tumour Xenografts (1986 Milan, Italy). Human tumour xenografts in anticancer drug development. Berlin: Springer-Verlag, 1988.

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R, Cutler Neal, ed. Accelerating CNS drug development. Chichester: John Wily & Sons, 1998.

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Rajagopal, Senthilkumar, and Saravanan Ramachandran. Zebrafish: A Model for Marine Peptide Based Drug Screening. Springer Singapore Pte. Limited, 2020.

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Rajagopal, Senthilkumar, and Saravanan Ramachandran. Zebrafish: A Model for Marine Peptide Based Drug Screening. Springer Singapore Pte. Limited, 2019.

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Haney, Steven A., Douglas Bowman, and Arijit Chakravarty. Introduction to High Content Screening. Wiley & Sons, Incorporated, John, 2014.

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van, Boxtel Christoffel Jos, Holford N. H. G, and Danhof M, eds. The In vivo study of drug action. Amsterdam: Elsevier, 1992.

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Willner, Paul. Behavioural Models in Psychopharmacology: Theoretical, Industrial and Clinical Perspectives. Cambridge University Press, 1991.

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Book chapters on the topic "Drug screening model"

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Joshi, Shantanu. "Zebrafish Model for Drug Discovery and Screening." In Zebrafish Model for Biomedical Research, 229–58. Singapore: Springer Nature Singapore, 2022. http://dx.doi.org/10.1007/978-981-16-5217-2_11.

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Bilginer, Rumeysa, and Ahu Arslan Yildiz. "Biomimetic Model Membranes as Drug Screening Platform." In Biomimetic Lipid Membranes: Fundamentals, Applications, and Commercialization, 225–47. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-11596-8_10.

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Li, Chunqi, Liqing Luo, and Patricia McGrath. "Zebrafish Xenotransplant Cancer Model for Drug Screening." In Zebrafish, 219–32. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2011. http://dx.doi.org/10.1002/9781118102138.ch17.

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Biswas, Snehasis, and Jayesh Bellare. "Zebrafish Model for Neurotoxic Drug Screening: Methodologies and Protocols." In Zebrafish Model for Biomedical Research, 467–90. Singapore: Springer Nature Singapore, 2022. http://dx.doi.org/10.1007/978-981-16-5217-2_21.

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Ramachandran, Saravanan, and Senthilkumar Rajagopal. "Teratogenic Activity of Peptides in Zebrafish Model." In Zebrafish: A Model for Marine Peptide Based Drug Screening, 15–25. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-7844-7_2.

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Ramachandran, Saravanan, and Senthilkumar Rajagopal. "Teratogenic Activity of Toxins in Zebrafish Model." In Zebrafish: A Model for Marine Peptide Based Drug Screening, 27–42. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-7844-7_3.

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Ramachandran, Saravanan, and Senthilkumar Rajagopal. "Anticancer Properties of Marine Peptides/Toxins Using Zebrafish Model." In Zebrafish: A Model for Marine Peptide Based Drug Screening, 43–53. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-7844-7_4.

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Ramachandran, Saravanan, and Senthilkumar Rajagopal. "Biomedical Importance of Marine Peptides/Toxins." In Zebrafish: A Model for Marine Peptide Based Drug Screening, 1–14. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-7844-7_1.

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Ramachandran, Saravanan, and Senthilkumar Rajagopal. "Protective Effect of Marine Peptides/Toxins in CVD Using Zebrafish Model." In Zebrafish: A Model for Marine Peptide Based Drug Screening, 55–73. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-7844-7_5.

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Gadige, Ambica, Narasimha Tanuj Gunturu, Amit Khurana, Prince Allawadhi, Isha Khurana, Anil Kumar Banothu, Sunitha Thalugula, Ramavath Redya Naik, and Kala Kumar Bharani. "Zebrafish as a Novel Pharmacological Screening Model for Drug Discovery and Development Against Hematological Disorders." In Zebrafish Model for Biomedical Research, 259–87. Singapore: Springer Nature Singapore, 2022. http://dx.doi.org/10.1007/978-981-16-5217-2_12.

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Conference papers on the topic "Drug screening model"

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Che, Chao, Min Zhu, Yongjun Zhu, Qiang Zhang, Dongsheng Zhou, and Bin Wang. "A Protein Embedding Model for Drug Molecular Screening." In 2020 IEEE International Conference on Big Data and Smart Computing (BigComp). IEEE, 2020. http://dx.doi.org/10.1109/bigcomp48618.2020.00-66.

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Girod, Vincent, Marie-Jose Ghoris, Jerome Vicogne, and Vincent Senez. "Microfluidic Culture Model for Drug Screening on Schistosome Parasites." In 2021 IEEE 34th International Conference on Micro Electro Mechanical Systems (MEMS). IEEE, 2021. http://dx.doi.org/10.1109/mems51782.2021.9375137.

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Ham, Stephanie L., Emily Mulvany, and Hossein Tavana. "Abstract 58: High throughput 3D tumor model drug screening technology." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-58.

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Ham, Stephanie L., Emily Mulvany, and Hossein Tavana. "Abstract 58: High throughput 3D tumor model drug screening technology." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-58.

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Benton, Gabriel J., Gerald DeGray, Irina Arnaoutova, Hynda K. Kleinman, and Jay George. "Abstract 324: High throughput triculture: A breast cancer spheroid model for drug screening." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-324.

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Tang, Yuan, Fariborz Soroush, Sudhir Deosarkar, Bin Wang, Balabhaskar Prabhakarpandian, and Mohammad Kiani. "Abstract 3382: A physiological model of the tumor microenvironment for screening drug delivery systems." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-3382.

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Tourlomousis, Filippos, and Robert C. Chang. "Computational Modeling of 3D Printed Tissue-on-a-Chip Microfluidic Devices as Drug Screening Platforms." In ASME 2014 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2014. http://dx.doi.org/10.1115/imece2014-38454.

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Physiological tissue-on-a-chip technology is enabled by adapting microfluidics to create micro scale drug screening platforms that replicate the complex drug transport and reaction processes in the human liver. The ability to incorporate three-dimensional (3d) tissue models using layered fabrication approaches into devices that can be perfused with drugs offer an optimal analog of the in vivo scenario. The dynamic nature of such in vitro metabolism models demands reliable numerical tools to determine the optimum tissue fabrication process, flow, material, and geometric parameters for the most effective metabolic conversion of the perfused drug into the liver microenvironment. Thus, in this modeling-based study, the authors focus on modeling of in vitro 3d microfluidic microanalytical microorgan devices (3MD), where the human liver analog is replicated by 3d cell encapsulated alginate hydrogel based tissue-engineered constructs. These biopolymer constructs are hosted in the chamber of the 3MD device serving as walls of the microfluidic array of channels through which a fluorescent drug substrate is perfused into the microfluidic printed channel walls at a specified volumetric flow rate assuring Stokes flow conditions (Re<<1). Due to the porous nature of the hydrogel walls, a metabolized drug product is collected as an effluent stream at the outlet port. A rigorous modeling approached aimed to capture both the macro and micro scale transport phenomena is presented. Initially, the Stokes Flow Equations (free flow regime) are solved in combination with the Brinkman Equations (porous flow regime) for the laminar velocity profile and wall shear stresses in the whole shear mediated flow regime. These equations are then coupled with the Convection-Diffusion Equation to yield the drug concentration profile by incorporating a reaction term described by the Michael-Menten Kinetics model. This effectively yields a convection-diffusion–cell kinetics model (steady state and transient), where for the prescribed process and material parameters, the drug concentration profile throughout the flow channels can be predicted. A key consideration that is addressed in this paper is the effect of cell mechanotransduction, where shear stresses imposed on the encapsulated cells alter the functional ability of the liver cell enzymes to metabolize the drug. Different cases are presented, where cells are incorporated into the geometric model either as voids that experience wall shear stress (WSS) around their membrane boundaries or as solid materials, with linear elastic properties. As a last step, transient simulations are implemented showing that there exists a tradeoff with respect the drug metabolized effluent product between the shear stresses required and the residence time needed for drug diffusion.
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Tourlomousis, Filippos, and Robert C. Chang. "2D and 3D Multiscale Computational Modeling of Dynamic Microorgan Devices as Drug Screening Platforms." In ASME 2015 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2015. http://dx.doi.org/10.1115/imece2015-52734.

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The ability to incorporate three-dimensional (3D) hepatocyte-laden hydrogel constructs using layered fabrication approaches into devices that can be perfused with drugs enables the creation of dynamic microorgan devices (DMDs) that offer an optimal analog of the in vivo liver metabolism scenario. The dynamic nature of such in vitro metabolism models demands reliable numerical tools to determine the optimum process, material, and geometric parameters for the most effective metabolic conversion of the perfused drug into the liver microenvironment. However, there is a current lack of literature that integrates computational approaches to guide the optimum design of such devices. The groundwork of the present numerical study has been laid by our previous study [1], where the authors modeled in 2D an in vitro DMD of arbitrary dimensions and identified the modeling challenges towards meaningful results. These constructs are hosted in the chamber of the microfluidic device serving as walls of the microfluidic array of channels through which a fluorescent drug substrate is perfused into the microfluidic printed channel walls at a specified volumetric flow rate assuring Stokes flow conditions (Re<<1). Due to the porous nature of the hydrogel walls, a metabolized drug product is collected at the outlet port. A rigorous FEM based modeling approach is presented for a single channel parallel model geometry (1 free flow channel with 2 porous walls), where the hydrodynamics, mass transfer and pharmacokinetics equations are solved numerically in order to yield the drug metabolite concentration profile at the DMD outlet. The fluid induces shear stresses are assessed both in 3D, with only 27 cells modeled as single compartment voids, where all of the enzymatic reactions are assumed to take place. In this way, the mechanotransduction effect that alters the hepatocyte metabolic activity is assessed for a small scale model. This approach overcomes the numerical limitations imposed by the cell density (∼1012 cells/m3) of the large scale DMD device. In addition, a compartmentalization technique is proposed in order to assess the metabolism process at the subcellular level. The numerical results are validated with experiments to reveal the robustness of the proposed modeling approach and the necessity of scaling the numerical results by preserving dynamic and biochemical similarity between the small and large scale model.
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Pellegrini, Paola, Martin Haraldsson, Annika Jenmalm Jensen, Thomas Lundbäck, and Angelo De Milito. "Abstract 5509: A drug-screening model to identify compounds active in cells under metabolic stress." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-5509.

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Heuchel, Rainer L., Salvatore Nania, Jianping Liu, and J. Matthias Löhr. "Abstract B43: High-throughput drug screening model using 3D cultured human pancreatic ductal adenocarcinoma cells." In Abstracts: AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; May 12-15, 2016; Orlando, FL. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.panca16-b43.

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Reports on the topic "Drug screening model"

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Bisoffi, Marco. Curcumin Based Drug Screening for Inhibitors of NF kappa B in a Cell Model of Prostate Cancer Progression. Fort Belvoir, VA: Defense Technical Information Center, February 2008. http://dx.doi.org/10.21236/ada482629.

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Cytryn, Eddie, Mark R. Liles, and Omer Frenkel. Mining multidrug-resistant desert soil bacteria for biocontrol activity and biologically-active compounds. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7598174.bard.

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Control of agro-associated pathogens is becoming increasingly difficult due to increased resistance and mounting restrictions on chemical pesticides and antibiotics. Likewise, in veterinary and human environments, there is increasing resistance of pathogens to currently available antibiotics requiring discovery of novel antibiotic compounds. These drawbacks necessitate discovery and application of microorganisms that can be used as biocontrol agents (BCAs) and the isolation of novel biologically-active compounds. This highly-synergistic one year project implemented an innovative pipeline aimed at detecting BCAs and associated biologically-active compounds, which included: (A) isolation of multidrug-resistant desert soil bacteria and root-associated bacteria from medicinal plants; (B) invitro screening of bacterial isolates against known plant, animal and human pathogens; (C) nextgeneration sequencing of isolates that displayed antagonistic activity against at least one of the model pathogens and (D) in-planta screening of promising BCAs in a model bean-Sclerotiumrolfsii system. The BCA genome data were examined for presence of: i) secondary metabolite encoding genes potentially linked to the anti-pathogenic activity of the isolates; and ii) rhizosphere competence-associated genes, associated with the capacity of microorganisms to successfully inhabit plant roots, and a prerequisite for the success of a soil amended BCA. Altogether, 56 phylogenetically-diverse isolates with bioactivity against bacterial, oomycete and fungal plant pathogens were identified. These strains were sent to Auburn University where bioassays against a panel of animal and human pathogens (including multi-drug resistant pathogenic strains such as A. baumannii 3806) were conducted. Nineteen isolates that showed substantial antagonistic activity against at least one of the screened pathogens were sequenced, assembled and subjected to bioinformatics analyses aimed at identifying secondary metabolite-encoding and rhizosphere competence-associated genes. The genome size of the bacteria ranged from 3.77 to 9.85 Mbp. All of the genomes were characterized by a plethora of secondary metabolite encoding genes including non-ribosomal peptide synthase, polyketidesynthases, lantipeptides, bacteriocins, terpenes and siderophores. While some of these genes were highly similar to documented genes, many were unique and therefore may encode for novel antagonistic compounds. Comparative genomic analysis of root-associated isolates with similar strains not isolated from root environments revealed genes encoding for several rhizospherecompetence- associated traits including urea utilization, chitin degradation, plant cell polymerdegradation, biofilm formation, mechanisms for iron, phosphorus and sulfur acquisition and antibiotic resistance. Our labs are currently writing a continuation of this feasibility study that proposes a unique pipeline for the detection of BCAs and biopesticides that can be used against phytopathogens. It will combine i) metabolomic screening of strains from our collection that contain unique secondary metabolite-encoding genes, in order to isolate novel antimicrobial compounds; ii) model plant-based experiments to assess the antagonistic capacities of selected BCAs toward selected phytopathogens; and iii) an innovative next-generation-sequencing based method to monitor the relative abundance and distribution of selected BCAs in field experiments in order to assess their persistence in natural agro-environments. We believe that this integrated approach will enable development of novel strains and compounds that can be used in large-scale operations.
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Shpigel, Nahum, Raul Barletta, Ilan Rosenshine, and Marcelo Chaffer. Identification and characterization of Mycobacterium paratuberculosis virulence genes expressed in vivo by negative selection. United States Department of Agriculture, January 2004. http://dx.doi.org/10.32747/2004.7696510.bard.

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Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of a severe inflammatory bowel disease (IBD) in ruminants, known as Johne’s disease or paratuberculosis. Johne’s disease is considered to be one of the most serious diseases affecting dairy cattle both in Israel and worldwide. Heavy economic losses are incurred by dairy farmers due to the severe effect of subclinical infection on milk production, fertility, lower disease resistance and early culling. Its influence in the United States alone is staggering, causing an estimated loss of $1.5 billion to the agriculture industry every year. Isolation of MAP from intestinal tissue and blood of Crohn's patients has lead to concern that it plays a potential pathogenic role in promoting human IDB including Crohn’s disease. There is great concern following the identification of the organism in animal products and shedding of the organism to the environment by subclinically infected animals. Little is known about the molecular basis for MAP virulence. The goal of the original proposed research was to identify MAP genes that are required for the critical stage of initial infection and colonization of ruminants’ intestine by MAP. We proposed to develop and use signature tag mutagenesis (STM) screen to find MAP genes that are specifically required for survival in ruminants upon experimental infection. This research projected was approved as one-year feasibility study to prove the ability of the research team to establish the animal model for mutant screening and alternative in-vitro cell systems. In Israel, neonatal goat kids were repeatedly inoculated with either one of the following organisms; MAP K-10 strain and three transposon mutants of K-10 which were produced and screened by the US PI. Six months after the commencement of inoculation we have necropsied the goats and taken multiple tissue samples from the jejunum, ileum and mesenteric lymph nodes. Both PCR and histopathology analysis indicated on efficient MAP colonization of all the inoculated animals. We have established several systems in the Israeli PI’s laboratory; these include using IS900 PCR for the identification of MAP and using HSP65-based PCR for the differentiation between MAV and MAP. We used Southern blot analysis for the differentiation among transposon mutants of K-10. In addition the Israeli PI has set up a panel of in-vitro screening systems for MAP mutants. These include assays to test adhesion, phagocytosis and survival of MAP to/within macrophages, assays that determine the rate of MAPinduced apoptosis of macrophages and MAP-induced NO production by macrophages, and assays testing the interference with T cell ã Interferon production and T cell proliferation by MAP infected macrophages (macrophage studies were done in BoMac and RAW cell lines, mouse peritoneal macrophages and bovine peripheral blood monocytes derived macrophages, respectively). All partners involved in this project feel that we are currently on track with this novel, highly challenging and ambitious research project. We have managed to establish the above described research systems that will clearly enable us to achieve the original proposed scientific objectives. We have proven ourselves as excellent collaborative groups with very high levels of complementary expertise. The Israeli groups were very fortunate to work with the US group and in a very short time period to master numerous techniques in the field of Mycobacterium research. The Israeli group has proven its ability to run this complicated animal model. This research, if continued, may elucidate new and basic aspects related to the pathogenesis MAP. In addition the work may identify new targets for vaccine and drug development. Considering the possibility that MAP might be a cause of human Crohn’s disease, better understanding of virulence mechanisms of this organism might also be of public health interest as well.
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Hajarizadeh, Behzad, Jennifer MacLachlan, Benjamin Cowie, and Gregory J. Dore. Population-level interventions to improve the health outcomes of people living with hepatitis B: an Evidence Check brokered by the Sax Institute for the NSW Ministry of Health, 2022. The Sax Institute, August 2022. http://dx.doi.org/10.57022/pxwj3682.

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Background An estimated 292 million people are living with chronic hepatitis B virus (HBV) infection globally, including 223,000 people in Australia. HBV diagnosis and linkage of people living with HBV to clinical care is suboptimal in Australia, with 27% of people living with HBV undiagnosed and 77% not receiving regular HBV clinical care. This systematic review aimed to characterize population-level interventions implemented to enhance all components of HBV care cascade and analyse the effectiveness of interventions. Review questions Question 1: What population-level interventions, programs or policy approaches have been shown to be effective in reducing the incidence of hepatitis B; and that may not yet be fully rolled out or evaluated in Australia demonstrate early effectiveness, or promise, in reducing the incidence of hepatitis B? Question 2: What population-level interventions and/or programs are effective at reducing disease burden for people in the community with hepatitis B? Methods Four bibliographic databases and 21 grey literature sources were searched. Studies were eligible for inclusion if the study population included people with or at risk of chronic HBV, and the study conducted a population-level interventions to decrease HBV incidence or disease burden or to enhance any components of HBV care cascade (i.e., diagnosis, linkage to care, treatment initiation, adherence to clinical care), or HBV vaccination coverage. Studies published in the past 10 years (since January 2012), with or without comparison groups were eligible for inclusion. Studies conducting an HBV screening intervention were eligible if they reported proportion of people participating in screening, proportion of newly diagnosed HBV (participant was unaware of their HBV status), proportion of people received HBV vaccination following screening, or proportion of participants diagnosed with chronic HBV infection who were linked to HBV clinical care. Studies were excluded if study population was less than 20 participants, intervention included a pharmaceutical intervention or a hospital-based intervention, or study was implemented in limited clinical services. The records were initially screened by title and abstract. The full texts of potentially eligible records were reviewed, and eligible studies were selected for inclusion. For each study included in analysis, the study outcome and corresponding 95% confidence intervals (95%CIs) were calculated. For studies including a comparison group, odds ratio (OR) and corresponding 95%CIs were calculated. Random effect meta-analysis models were used to calculate the pooled study outcome estimates. Stratified analyses were conducted by study setting, study population, and intervention-specific characteristics. Key findings A total of 61 studies were included in the analysis. A large majority of studies (study n=48, 79%) included single-arm studies with no concurrent control, with seven (12%) randomised controlled trials, and six (10%) non-randomised controlled studies. A total of 109 interventions were evaluated in 61 included studies. On-site or outreach HBV screening and linkage to HBV clinical care coordination were the most frequent interventions, conducted in 27 and 26 studies, respectively. Question 1 We found no studies reporting HBV incidence as the study outcome. One study conducted in remote area demonstrated that an intervention including education of pregnant women and training village health volunteers enhanced coverage of HBV birth dose vaccination (93% post-intervention, vs. 81% pre-intervention), but no data of HBV incidence among infants were reported. Question 2 Study outcomes most relevant to the HBV burden for people in the community with HBV included, HBV diagnosis, linkage to HBV care, and HBV vaccination coverage. Among randomised controlled trials aimed at enhancing HBV screening, a meta-analysis was conducted including three studies which implemented an intervention including community face-to-face education focused on HBV and/or liver cancer among migrants from high HBV prevalence areas. This analysis demonstrated a significantly higher HBV testing uptake in intervention groups with the likelihood of HBV testing 3.6 times higher among those participating in education programs compared to the control groups (OR: 3.62, 95% CI 2.72, 4.88). In another analysis, including 25 studies evaluating an intervention to enhance HBV screening, a pooled estimate of 66% of participants received HBV testing following the study intervention (95%CI: 58-75%), with high heterogeneity across studies (range: 17-98%; I-square: 99.9%). A stratified analysis by HBV screening strategy demonstrated that in the studies providing participants with on-site HBV testing, the proportion receiving HBV testing (80%, 95%CI: 72-87%) was significantly higher compared to the studies referring participants to an external site for HBV testing (54%, 95%CI: 37-71%). In the studies implementing an intervention to enhance linkage of people diagnosed with HBV infection to clinical care, the interventions included different components and varied across studies. The most common component was post-test counselling followed by assistance with scheduling clinical appointments, conducted in 52% and 38% of the studies, respectively. In meta-analysis, a pooled estimate of 73% of people with HBV infection were linked to HBV clinical care (95%CI: 64-81%), with high heterogeneity across studies (range: 28-100%; I-square: 99.2%). A stratified analysis by study population demonstrated that in the studies among general population in high prevalence countries, 94% of people (95%CI: 88-100%) who received the study intervention were linked to care, significantly higher than 72% (95%CI: 61-83%) in studies among migrants from high prevalence area living in a country with low prevalence. In 19 studies, HBV vaccination uptake was assessed after an intervention, among which one study assessed birth dose vaccination among infants, one study assessed vaccination in elementary school children and 17 studies assessed vaccination in adults. Among studies assessing adult vaccination, a pooled estimate of 38% (95%CI: 21-56%) of people initiated vaccination, with high heterogeneity across studies (range: 0.5-93%; I square: 99.9%). A stratified analysis by HBV vaccination strategy demonstrated that in the studies providing on-site vaccination, the uptake was 78% (95%CI: 62-94%), significantly higher compared to 27% (95%CI: 13-42%) in studies referring participants to an external site for vaccination. Conclusion This systematic review identified a wide variety of interventions, mostly multi-component interventions, to enhance HBV screening, linkage to HBV clinical care, and HBV vaccination coverage. High heterogeneity was observed in effectiveness of interventions in all three domains of screening, linkage to care, and vaccination. Strategies identified to boost the effectiveness of interventions included providing on-site HBV testing and vaccination (versus referral for testing and vaccination) and including community education focussed on HBV or liver cancer in an HBV screening program. Further studies are needed to evaluate the effectiveness of more novel interventions (e.g., point of care testing) and interventions specifically including Indigenous populations, people who inject drugs, men who have sex with men, and people incarcerated.
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