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  1. Article ; Online: Simultaneous Focal Boost With Stereotactic Radiation Therapy for Localized Intermediate- to High-Risk Prostate Cancer: Primary Outcomes of the SPARC Phase 2 Trial.

    Yasar, Binnaz / Suh, Yae-Eun / Chapman, Ewan / Nicholls, Luke / Henderson, Daniel / Jones, Caroline / Morrison, Kirsty / Wells, Emma / Henderson, Julia / Meehan, Carole / Sohaib, Aslam / Taylor, Helen / Tree, Alison / van As, Nicholas

    International journal of radiation oncology, biology, physics

    2024  

    Abstract: Purpose: Dose-escalated radiation therapy is associated with better biochemical control at the expense of toxicity. Stereotactic body radiation therapy (SBRT) with dose escalation to the dominant intraprostatic lesion (DIL) provides a logical approach ... ...

    Abstract Purpose: Dose-escalated radiation therapy is associated with better biochemical control at the expense of toxicity. Stereotactic body radiation therapy (SBRT) with dose escalation to the dominant intraprostatic lesion (DIL) provides a logical approach to improve outcomes in high-risk disease while limiting toxicity. This study evaluated the toxicity and quality of life (QoL) with CyberKnife-based SBRT and simultaneous integrated boost in localized prostate cancer.
    Methods and materials: Eligible participants included newly diagnosed, biopsy-proven unfavorable intermediate- to high-risk localized prostate cancer (at least 1 of the following: Gleason ≥4+3, magnetic resonance imaging(MRI)-defined T3a N0, prostate-specific antigen ≥20) with up to 2 MRI-identified DILs. Participants received 36.25 Gy in 5 fractions on alternative days with a simultaneous boost to DIL up to 47.5 Gy as allowed by organ-at-risk constraints delivered by CyberKnife. All participants received androgen deprivation therapy. The primary outcome measure was acute grade 2+ genitourinary toxicity. Acute and late genitourinary and gastrointestinal toxicity using Radiation Therapy Oncology Group scoring, biochemical parameters, International Prostate Symptom Score, International Index of Erectile Function 5, and EQ-5D QoL outcomes were assessed.
    Results: Between 2013 and 2023, 20 participants were enrolled with a median follow-up of 30 months. The median D95 dose to DIL was 47.43 Gy. Cumulative acute grade 2+ genitourinary and gastrointestinal toxicity were 25% and 30%, respectively. One patient developed acute grade 3 genitourinary toxicity (5%). There is no late grade 3 genitourinary or gastrointestinal toxicity to date. International Prostate Symptom Score and urinary QoL scores recovered to baseline by 6 months. Patient-reported outcomes showed no significant change in EQ-5D QoL scores at 12 weeks and 1 year. There are no cases of biochemical relapse reported to date.
    Conclusions: CyberKnife SBRT-delivered dose of 36.25 Gy to the prostate with a simultaneous integrated boost up to 47.5 Gy is well tolerated. Acute and late genitourinary and gastrointestinal toxicity rates are comparable to other contemporary SBRT trials and series with focal boost.
    Language English
    Publishing date 2024-03-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 197614-x
    ISSN 1879-355X ; 0360-3016
    ISSN (online) 1879-355X
    ISSN 0360-3016
    DOI 10.1016/j.ijrobp.2024.03.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Corrigendum: Inhibition of phosphodiesterase 12 results in antiviral activity against several RNA viruses including SARS-CoV-2.

    Thursz, Mark / Sadiq, Fouzia / Tree, Julia A / Karayiannis, Peter / Beasley, David W C / Dejnirattisai, Wanwissa / Mongkolsapaya, Juthathip / Screaton, Gavin / Wand, Matthew / Elmore, Michael J / Carroll, Miles W / Matthews, Ian / Thomas, Howard

    The Journal of general virology

    2023  Volume 104, Issue 7

    Language English
    Publishing date 2023-07-25
    Publishing country England
    Document type Journal Article ; Published Erratum
    ZDB-ID 219316-4
    ISSN 1465-2099 ; 0022-1317
    ISSN (online) 1465-2099
    ISSN 0022-1317
    DOI 10.1099/jgv.0.001876
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Interim Toxicity Analysis From the Randomized HERMES Trial of 2- and 5-Fraction Magnetic Resonance Imaging-Guided Adaptive Prostate Radiation Therapy.

    Westley, Rosalyne Laura / Biscombe, Katie / Dunlop, Alex / Mitchell, Adam / Oelfke, Uwe / Nill, Simeon / Murray, Julia / Pathmanathan, Angela / Hafeez, Shaista / Parker, Chris / Ratnakumaran, Ragu / Alexander, Sophie / Herbert, Trina / Hall, Emma / Tree, Alison C

    International journal of radiation oncology, biology, physics

    2023  Volume 118, Issue 3, Page(s) 682–687

    Abstract: Purpose: Ultrahypofractionated radiation therapy (UHRT) is an effective treatment for localized prostate cancer with an acceptable toxicity profile; boosting the visible intraprostatic tumor has been shown to improve biochemical disease-free survival ... ...

    Abstract Purpose: Ultrahypofractionated radiation therapy (UHRT) is an effective treatment for localized prostate cancer with an acceptable toxicity profile; boosting the visible intraprostatic tumor has been shown to improve biochemical disease-free survival with no significant effect on genitourinary (GU) and gastrointestinal (GI) toxicity.
    Methods and materials: HERMES is a single-center noncomparative randomized phase 2 trial in men with intermediate or lower high risk prostate cancer. Patients were allocated (1:1) to 36.25 Gy in 5 fractions over 2 weeks or 24 Gy in 2 fractions over 8 days with an integrated boost to the magnetic resonance imaging (MRI) visible tumor of 27 Gy in 2 fractions. A minimization algorithm with a random element with risk group as a balancing factor was used for participant randomization. Treatment was delivered on the Unity MR-Linac (Elekta AB) with daily online adaption. The primary endpoint was acute GU Common Terminology Criteria for Adverse Events version 5.0 toxicity with the aim of excluding a doubling of the rate of acute grade 2+ GU toxicity seen in PACE. Analysis was by treatment received and included all participants who received at least 1 fraction of study treatment. This interim analysis was prespecified (stage 1 of a 2-stage Simon design) for when 10 participants in each treatment group had completed the acute toxicity monitoring period (12 weeks after radiation therapy).
    Results: Acute grade 2 GU toxicity was reported in 1 (10%) patient in the 5-fraction group and 2 (20%) patients in the 2-fraction group. No grade 3+ GU toxicities were reported.
    Conclusions: At this interim analysis, the rate of GU toxicity in the 2-fraction and 5-fraction treatment groups was found to be below the prespecified threshold (5/10 grade 2+) and continuation of the study to complete recruitment of 23 participants per group was recommended.
    MeSH term(s) Humans ; Male ; Gastrointestinal Diseases ; Magnetic Resonance Imaging ; Pelvis ; Prostate/pathology ; Prostatic Neoplasms/diagnostic imaging ; Prostatic Neoplasms/radiotherapy ; Prostatic Neoplasms/pathology ; Urogenital System/radiation effects ; Randomized Controlled Trials as Topic ; Clinical Trials, Phase II as Topic
    Language English
    Publishing date 2023-09-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 197614-x
    ISSN 1879-355X ; 0360-3016
    ISSN (online) 1879-355X
    ISSN 0360-3016
    DOI 10.1016/j.ijrobp.2023.09.032
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Linked Mutations in the Ebola Virus Polymerase Are Associated with Organ Specific Phenotypes.

    Dong, Xiaofeng / Tree, Julia / Banadyga, Logan / He, Shihua / Zhu, Wenjun / Tipton, Tom / Gouriet, Jade / Qiu, Xiangguo / Elmore, Michael J / Hall, Yper / Carroll, Miles / Hiscox, Julian A

    Microbiology spectrum

    2023  , Page(s) e0415422

    Abstract: Ebola virus (EBOV) causes a severe infection called Ebola virus disease (EVD). The pathogenesis of EBOV infection is complex, and outcome has been associated with a variety of immunological and cellular factors. Disease can result from several mechanisms, ...

    Abstract Ebola virus (EBOV) causes a severe infection called Ebola virus disease (EVD). The pathogenesis of EBOV infection is complex, and outcome has been associated with a variety of immunological and cellular factors. Disease can result from several mechanisms, including direct organ and endothelial cell damage as a result of viral replication. During the2013 to 2016 Western Africa EBOV outbreak, several mutants emerged, with changes in the genes of nucleoprotein (NP), glycoprotein (GP), and the large (L) protein. Reverse genetic analysis has been used to investigate whether these mutations played any role in pathogenesis with mixed results depending on the experimental system used. Previous studies investigated the impact of three single nonsynonymous mutations (GP-A82V, NP-R111C, and L-D759G) on the fatality rate of mouse and ferret models and suggested that the L-D759G mutation decreased the virulence of EBOV. In this study, the effect of these three mutations was further evaluated by deep sequencing to determine viral population genetics and the host response in longitudinal samples of blood, liver, kidney, spleen, and lung tissues taken from the previous ferret model. The data indicated that the mutations were maintained in the different tissues, but the frequency of minor genomic mutations were different. In addition, compared to wild-type virus, the recombinant mutants had different within host effects, where the D759G (and accompanying Q986H) substitution in the L protein resulted in an upregulation of the immune response in the kidney, liver, spleen, and lungs. Together these studies provide insights into the biology of EBOV mutants both between and within hosts.
    Language English
    Publishing date 2023-03-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/spectrum.04154-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Inhibition of phosphodiesterase 12 results in antiviral activity against several RNA viruses including SARS-CoV-2.

    Thursz, Mark / Sadiq, Fouzia / Tree, Julia A / Karayiannis, Peter / Beasley, David W C / Dejnirattisai, Wanwissa / Mongkolsapaya, Juthathip / Screaton, Gavin / Wand, Matthew / Elmore, Michael J / Carroll, Miles W / Matthews, Ian / Thomas, Howard

    The Journal of general virology

    2023  Volume 104, Issue 7

    Abstract: The 2',5'- oligoadenylate synthetase (OAS) - ribonuclease L (RNAseL) - phosphodiesterase 12 (PDE12) pathway is an essential interferon-induced effector mechanism against RNA virus infection. Inhibition of PDE12 leads to selective amplification of RNAseL ... ...

    Abstract The 2',5'- oligoadenylate synthetase (OAS) - ribonuclease L (RNAseL) - phosphodiesterase 12 (PDE12) pathway is an essential interferon-induced effector mechanism against RNA virus infection. Inhibition of PDE12 leads to selective amplification of RNAseL activity in infected cells. We aimed to investigate PDE12 as a potential pan-RNA virus antiviral drug target and develop PDE12 inhibitors that elicit antiviral activity against a range of viruses. A library of 18 000 small molecules was screened for PDE12 inhibitor activity using a fluorescent probe specific for PDE12. The lead compounds (CO-17 or CO-63) were tested in cell-based antiviral assays using encephalomyocarditis virus (EMCV), hepatitis C virus (HCV), dengue virus (DENV), West Nile virus (WNV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),
    MeSH term(s) Humans ; Mice ; Animals ; Rats ; Antiviral Agents/pharmacology ; SARS-CoV-2 ; COVID-19 ; RNA Viruses ; Interferon-alpha ; Encephalomyocarditis virus ; Phosphoric Diester Hydrolases
    Chemical Substances Antiviral Agents ; diethylstilbestrol monophosphate (47341-71-9) ; Interferon-alpha ; Phosphoric Diester Hydrolases (EC 3.1.4.-)
    Language English
    Publishing date 2023-07-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 219316-4
    ISSN 1465-2099 ; 0022-1317
    ISSN (online) 1465-2099
    ISSN 0022-1317
    DOI 10.1099/jgv.0.001865
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Prostate cancer - Advantages and disadvantages of MR-guided RT.

    Murray, Julia / Tree, Alison C

    Clinical and translational radiation oncology

    2019  Volume 18, Page(s) 68–73

    Abstract: External beam radiotherapy for prostate cancer is an optimal treatment choice for men with localised prostate cancer and is associated with long term disease control in most patients. Image-guided prostate radiotherapy is standard of care, however, ... ...

    Abstract External beam radiotherapy for prostate cancer is an optimal treatment choice for men with localised prostate cancer and is associated with long term disease control in most patients. Image-guided prostate radiotherapy is standard of care, however, current techniques can include invasive procedures with imaging of poor soft tissue resolution, thus limiting accuracy. MRI is the imaging of choice for local prostate cancer staging and in radiotherapy planning has been shown to reduce target volume and reduce inter-observer prostate contouring variability. The ultimate aim would be to have a MR-only workflow for prostate radiotherapy. Within this article, we discuss these opportunities and challenges, relevant due to the increasing availability of MR-guided radiotherapy. Prospective multi-centre studies are underway to determine the feasibility of MR-guided prostate radiotherapy and daily adaptive replanning. In parallel, development and adaptation of the existing radiotherapy multidisciplinary workforce is essential to enable an efficient and effective MR-guided radiotherapy workflow. This technology potentially provides us with the anatomical and biological information to further improve outcomes for our patients.
    Language English
    Publishing date 2019-04-01
    Publishing country Ireland
    Document type Journal Article ; Review
    ISSN 2405-6308
    ISSN (online) 2405-6308
    DOI 10.1016/j.ctro.2019.03.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Publisher Correction: Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab')

    Findlay-Wilson, Stephen / Easterbrook, Linda / Smith, Sandra / Pope, Neville / Aldridge, Matthew / Humphries, Gareth / Schuhmann, Holger / Ngabo, Didier / Rayner, Emma / Otter, Ashley / Coleman, Thomas / Hicks, Bethany / Halkerston, Rachel / Apostolakis, Kostis / Taylor, Stephen / Fotheringham, Susan / Horton, Amanda / CanoCejas, Irene / Wand, Matthew /
    Tree, Julia A / Sutton, Mark / Graham, Victoria / Hewson, Roger / Dowall, Stuart

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 15419

    Language English
    Publishing date 2023-09-18
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-42526-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Oligoprogression in Metastatic, Castrate-Resistant Prostate Cancer-Prevalence and Current Clinical Practice.

    Patel, Priyanka H / Tunariu, Nina / Levine, Daniel S / de Bono, Johann S / Eeles, Rosalind A / Khoo, Vincent / Murray, Julia / Parker, Christopher C / Pathmanathan, Angela / Reid, Alison / van As, Nicholas / Tree, Alison C

    Frontiers in oncology

    2022  Volume 12, Page(s) 862995

    Abstract: Aims: Oligoprogression is poorly defined in current literature. Little is known about the natural history and significance of oligoprogression in patients with hormone-resistant prostate cancer on abiraterone or enzalutamide treatment [termed androgen ... ...

    Abstract Aims: Oligoprogression is poorly defined in current literature. Little is known about the natural history and significance of oligoprogression in patients with hormone-resistant prostate cancer on abiraterone or enzalutamide treatment [termed androgen receptor-targeted therapy (ARTT)]. The aim of this study was to determine the prevalence of oligoprogression, describe the characteristics of oligoprogression in a cohort of patients from a single center, and identify the number of patients potentially treatable with stereotactic body radiotherapy (SBRT).
    Methods: Castration-resistant prostate cancer (CRPC) patients who radiologically progressed while on ARTT were included. Patients with oligoprogressive disease (OPD) (≤3 lesions) on any imaging were identified in a retrospective analysis of electronic patient records. Kaplan-Meier method and log-rank test were used to calculate progression-free and overall survival.
    Results: A total of 102 patients with metastatic CRPC on ARTT were included. Thirty (29%) patients presented with oligoprogression (46 lesions in total); 21 (21% of total) patients had lesions suitable for SBRT. The majority of lesions were in the bone (21, 46%) or lymph nodes (15, 33%). Patients with oligoprogression while on ARTT had a significantly better prostate-specific antigen (PSA) response on commencing ARTT as compared to patients who later developed polyprogression. However, PSA doubling time immediately prior to progression did not predict OPD. Median progression-free survival to oligoprogression versus polyprogression was 16.8 vs. 11.7 months. Time to further progression after oligoprogression was 13.6 months in those treated with radiotherapy (RT) for oligoprogression vs. 5.7 months in those treated with the continuation of ARTT alone.
    Conclusions: In this study, nearly a third of patients on ARTT for CRPC were found to have OPD. OPD patients had a better PSA response on ART and a longer duration on ARTT before developing OPD as compared to those developing polyprogressive disease (Poly-PD). The majority of patients (70%) with OPD had lesions suitable for SBRT treatment. Prospective randomized control trials are needed to establish if there is a survival benefit of SBRT in oligoprogressive prostate cancer and to determine predictive indicators.
    Language English
    Publishing date 2022-05-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.862995
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  9. Article ; Online: Standard and Hypofractionated Dose Escalation to Intraprostatic Tumor Nodules in Localized Prostate Cancer: 5-Year Efficacy and Toxicity in the DELINEATE Trial.

    Tree, Alison C / Satchwell, Laura / Alexander, Emma / Blasiak-Wal, Irena / deSouza, Nandita M / Gao, Annie / Greenlay, Emily / McNair, Helen / Parker, Chris / Talbot, James / Dearnaley, David / Murray, Julia

    International journal of radiation oncology, biology, physics

    2022  Volume 115, Issue 2, Page(s) 305–316

    Abstract: Purpose: Our purpose was to report 5-year efficacy and toxicity of intraprostatic lesion boosting using standard and hypofractionated radiation therapy.: Methods and materials: DELINEATE (ISRCTN 04483921) is a single center phase 2 multicohort study ... ...

    Abstract Purpose: Our purpose was to report 5-year efficacy and toxicity of intraprostatic lesion boosting using standard and hypofractionated radiation therapy.
    Methods and materials: DELINEATE (ISRCTN 04483921) is a single center phase 2 multicohort study including standardly fractionated (cohort A: 74 Gy/37F to prostate and seminal vesicles [PSV]; cohort C 74 Gy/37F to PSV plus 60 Gy/37F to pelvic lymph nodes) and moderately hypofractionated (cohort B: 60 Gy/20F to PSV) prostate intensity-modulated radiation therapy patients with National Comprehensive Cancer Network intermediate/high-risk disease. Patients received an integrated boost of 82 Gy (cohorts A and C) or 67 Gy (cohort B) to multiparametric magnetic resonance imaging identified lesion(s). Primary endpoint was late Radiation Therapy Oncology Group (RTOG) gastrointestinal (GI) toxicity at 1 year. Secondary endpoints were acute and late toxicity (clinician and patient reported) and freedom from biochemical/clinical failure at 5 years.
    Results: Two hundred and sixty-five men were recruited and 256 were treated (55 cohort A, 153 cohort B, and 48 cohort C). Median follow-up for each cohort was >5 years. Cumulative late RTOG grade 2+ GI toxicity at 1 year was 3.6% (95% confidence interval [CI], 0.9%-13.8%) (cohort A), 7.2% (95% CI, 4%-12.6%) (cohort B), and 8.4% (95% CI, 3.2%-20.8%) (cohort C). Cumulative late RTOG grade 2+ GI toxicity to 5 years was 12.8% (95% CI, 6.3%-25.1%) (cohort A), 14.6% (95% CI, 9.9%-21.4%) (cohort B), and 20.7% (95% CI, 11.2%-36.2%) (cohort C). Cumulative RTOG grade 2+ genitourinary toxicity to 5 years was 12.9% (95% CI, 6.4%-25.2%) (cohort A), 18.2% (95% CI, 12.8%-25.4%) (cohort B), and 18.2% (95% CI, 9.5%-33.2%) (cohort C). Five-year freedom from biochemical/clinical failure was 98.2% (95% CI, 87.8%-99.7%) (cohort A), 96.7% (95% CI, 91.3%- 98.8%) (cohort B), and 95.1% (95% CI, 81.6-98.7%) (cohort C).
    Conclusions: The DELINEATE trial has shown safety, tolerability, and feasibility of focal boosting in 20 or 37 fractions. Efficacy results indicate a low chance of prostate cancer recurrence 5 years after radiation therapy. Evidence from ongoing phase 3 randomized trials is awaited.
    MeSH term(s) Humans ; Male ; Gastrointestinal Diseases/etiology ; Neoplasm Recurrence, Local/etiology ; Prostate/pathology ; Prostatic Neoplasms/pathology ; Radiation Dose Hypofractionation ; Radiotherapy, Intensity-Modulated/adverse effects ; Radiotherapy, Intensity-Modulated/methods
    Language English
    Publishing date 2022-09-21
    Publishing country United States
    Document type Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 197614-x
    ISSN 1879-355X ; 0360-3016
    ISSN (online) 1879-355X
    ISSN 0360-3016
    DOI 10.1016/j.ijrobp.2022.09.058
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab')

    Findlay-Wilson, Stephen / Easterbrook, Linda / Smith, Sandra / Pope, Neville / Aldridge, Matthew / Humphries, Gareth / Schuhmann, Holger / Ngabo, Didier / Rayner, Emma / Otter, Ashley / Coleman, Thomas / Hicks, Bethany / Halkerston, Rachel / Apostolakis, Kostis / Taylor, Stephen / Fotheringham, Susan / Horton, Amanda / CanoCejas, Irene / Wand, Matthew /
    Tree, Julia A / Sutton, Mark / Graham, Victoria / Hewson, Roger / Dowall, Stuart

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 13912

    Abstract: The development of new therapies against SARS-CoV-2 is required to extend the toolkit of intervention strategies to combat the global pandemic. In this study, hyperimmune plasma from sheep immunised with whole spike SARS-CoV-2 recombinant protein has ... ...

    Abstract The development of new therapies against SARS-CoV-2 is required to extend the toolkit of intervention strategies to combat the global pandemic. In this study, hyperimmune plasma from sheep immunised with whole spike SARS-CoV-2 recombinant protein has been used to generate candidate products. In addition to purified IgG, we have refined candidate therapies by removing non-specific IgG via affinity binding along with fragmentation to eliminate the Fc region to create F(ab')
    MeSH term(s) Cricetinae ; Animals ; Sheep ; SARS-CoV-2 ; COVID-19 ; Immunization, Passive ; Kinetics ; Immunoglobulin G
    Chemical Substances Immunoglobulin G
    Language English
    Publishing date 2023-08-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-40277-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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