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Article: Prodrug Therapies for Infectious and Neurodegenerative Diseases.

Markovic, Milica / Deodhar, Suyash / Machhi, Jatin / Yeapuri, Pravin / Saleh, Maamoon / J Edagwa, Benson / Mosley, Rodney Lee / Gendelman, Howard E

Pharmaceutics

2022 Volume 14, Issue 3

Abstract: Prodrugs are bioreversible drug derivatives which are metabolized into a pharmacologically active drug following chemical or enzymatic modification. This approach is designed to overcome several obstacles that are faced by the parent drug in ... ...

Abstract	Prodrugs are bioreversible drug derivatives which are metabolized into a pharmacologically active drug following chemical or enzymatic modification. This approach is designed to overcome several obstacles that are faced by the parent drug in physiological conditions that include rapid drug metabolism, poor solubility, permeability, and suboptimal pharmacokinetic and pharmacodynamic profiles. These suboptimal physicochemical features can lead to rapid drug elimination, systemic toxicities, and limited drug-targeting to disease-affected tissue. Improving upon these properties can be accomplished by a prodrug design that includes the careful choosing of the promoiety, the linker, the prodrug synthesis, and targeting decorations. We now provide an overview of recent developments and applications of prodrugs for treating neurodegenerative, inflammatory, and infectious diseases. Disease interplay reflects that microbial infections and consequent inflammation affects neurodegenerative diseases and vice versa, independent of aging. Given the high prevalence, personal, social, and economic burden of both infectious and neurodegenerative disorders, therapeutic improvements are immediately needed. Prodrugs are an important, and might be said a critical tool, in providing an avenue for effective drug therapy.
Language	English
Publishing date	2022-02-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14030518
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Article ; Online: Monocyte biomarkers define sargramostim treatment outcomes for Parkinson's disease.

Abdelmoaty, Mai M / Machhi, Jatin / Yeapuri, Pravin / Shahjin, Farah / Kumar, Vikas / Olson, Katherine E / Mosley, R Lee / Gendelman, Howard E

Clinical and translational medicine

2022 Volume 12, Issue 7, Page(s) e958

Abstract: Background: Dysregulation of innate and adaptive immunity heralds both the development and progression of Parkinson's disease (PD). Deficits in innate immunity in PD are defined by impairments in monocyte activation, function, and pro-inflammatory ... ...

Abstract	Background: Dysregulation of innate and adaptive immunity heralds both the development and progression of Parkinson's disease (PD). Deficits in innate immunity in PD are defined by impairments in monocyte activation, function, and pro-inflammatory secretory factors. Each influences disease pathobiology. Methods and results: To define monocyte biomarkers associated with immune transformative therapy for PD, changes in gene and protein expression were evaluated before and during treatment with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim, Leukine Conclusions: This monocyte profile provides an "early" and unique biomarker strategy to track clinical immune-based interventions, but requiring validation in larger case studies.
MeSH term(s)	Biomarkers ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use ; Humans ; Monocytes/metabolism ; Parkinson Disease/drug therapy ; Parkinson Disease/metabolism ; Proteomics ; Recombinant Proteins ; Treatment Outcome
Chemical Substances	Biomarkers ; Recombinant Proteins ; sargramostim (5TAA004E22) ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
Language	English
Publishing date	2022-07-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2697013-2
ISSN	2001-1326 ; 2001-1326
ISSN (online)	2001-1326
ISSN	2001-1326
DOI	10.1002/ctm2.958
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Article ; Online: Amyloid-β specific regulatory T cells attenuate Alzheimer's disease pathobiology in APP/PS1 mice.

Yeapuri, Pravin / Machhi, Jatin / Lu, Yaman / Abdelmoaty, Mai Mohamed / Kadry, Rana / Patel, Milankumar / Bhattarai, Shaurav / Lu, Eugene / Namminga, Krista L / Olson, Katherine E / Foster, Emma G / Mosley, R Lee / Gendelman, Howard E

Molecular neurodegeneration

2023 Volume 18, Issue 1, Page(s) 97

Abstract: Background: Regulatory T cells (Tregs) maintain immune tolerance. While Treg-mediated neuroprotective activities are now well-accepted, the lack of defined antigen specificity limits their therapeutic potential. This is notable for neurodegenerative ... ...

Abstract	Background: Regulatory T cells (Tregs) maintain immune tolerance. While Treg-mediated neuroprotective activities are now well-accepted, the lack of defined antigen specificity limits their therapeutic potential. This is notable for neurodegenerative diseases where cell access to injured brain regions is required for disease-specific therapeutic targeting and improved outcomes. To address this need, amyloid-beta (Aβ) antigen specificity was conferred to Treg responses by engineering the T cell receptor (TCR) specific for Aβ (TCR Methods: TCR Results: TCR Conclusions: TCR
MeSH term(s)	Animals ; Humans ; Mice ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/genetics ; Amyloid beta-Protein Precursor/metabolism ; Amyloidogenic Proteins ; Disease Models, Animal ; Mice, Transgenic ; Presenilin-1/genetics ; Receptors, Antigen, T-Cell ; T-Lymphocytes, Regulatory
Chemical Substances	Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Amyloidogenic Proteins ; Presenilin-1 ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2023-12-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2244557-2
ISSN	1750-1326 ; 1750-1326
ISSN (online)	1750-1326
ISSN	1750-1326
DOI	10.1186/s13024-023-00692-7
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Article ; Online: Immune senescence in aged APP/PS1 mice.

Abdelmoaty, Mai M / Yeapuri, Pravin / Machhi, Jatin / Lu, Yaman / Namminga, Krista L / Kadry, Rana / Lu, Eugene / Bhattarai, Shaurav / Mosley, Rodney Lee / Gendelman, Howard E

NeuroImmune pharmacology and therapeutics

2023 Volume 2, Issue 3, Page(s) 317–330

Abstract: Objectives: To evaluate the linkage between age and deficits in innate and adaptive immunity which heralds both Alzheimer's disease (AD) onset and progression. The pathobiological events which underlie and tie these outcomes remain not fully understood.! ...

Abstract	Objectives: To evaluate the linkage between age and deficits in innate and adaptive immunity which heralds both Alzheimer's disease (AD) onset and progression. The pathobiological events which underlie and tie these outcomes remain not fully understood. Methods: To investigate age-dependent immunity in AD, we evaluated innate and adaptive immunity in coordinate studies of regulatory T cell (Treg) function, T cell frequencies, and microglial integrity. These were assessed in blood, peripheral lymphoid tissues, and the hippocampus of transgenic (Tg) amyloid precursor protein/presenilin 1 (APP/PS1) against non-Tg mice. Additionally, immune arrays of hippocampal tissue were performed at 4, 6, 12, and 20 months of age. Results: APP/PS1 mice showed progressive impairment of Treg immunosuppressive function with age. There was partial restoration of Treg function in 20-month-old mice. Ingenuity pathway analyses of hippocampal tissues were enriched in inflammatory, oxidative, and cellular activation pathways that paralleled advancing age and AD-pathobiology. Operative genes in those pathways included, but were not limited to triggering receptor on myeloid cells 1 (TREM1), T helper type 1 (Th1), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways. Interleukin-17 (IL-17), nitric oxide, acute phase, and T cell receptor signaling pathways were also perturbed. Significant inflammation was observed at 6- and 12-months. However, at 20-months, age associated partial restoration of Treg function reduced inflammatory phenotype. Conclusions: Impaired Treg function, inflammation and oxidative stress were associated with AD pathology. Age associated partial restoration of Treg function in old mice reduced the hippocampal inflammatory phenotype. Restoring Treg suppressive function can be a therapeutic modality for AD.
Language	English
Publishing date	2023-08-14
Publishing country	Germany
Document type	Journal Article
ISSN	2750-6665
ISSN (online)	2750-6665
DOI	10.1515/nipt-2023-0015
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Article ; Online: Monocyte biomarkers define sargramostim treatment outcomes for Parkinson's disease

Mai M. Abdelmoaty / Jatin Machhi / Pravin Yeapuri / Farah Shahjin / Vikas Kumar / Katherine E. Olson / R. Lee Mosley / Howard E. Gendelman

Clinical and Translational Medicine, Vol 12, Iss 7, Pp n/a-n/a (2022)

2022

Abstract: Abstract Background Dysregulation of innate and adaptive immunity heralds both the development and progression of Parkinson's disease (PD). Deficits in innate immunity in PD are defined by impairments in monocyte activation, function, and pro‐ ... ...

Abstract	Abstract Background Dysregulation of innate and adaptive immunity heralds both the development and progression of Parkinson's disease (PD). Deficits in innate immunity in PD are defined by impairments in monocyte activation, function, and pro‐inflammatory secretory factors. Each influences disease pathobiology. Methods and Results To define monocyte biomarkers associated with immune transformative therapy for PD, changes in gene and protein expression were evaluated before and during treatment with recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF, sargramostim, Leukine®). Monocytes were recovered after leukapheresis and isolation by centrifugal elutriation, before and 2 and 6 months after initiation of treatment. Transcriptome and proteome biomarkers were scored against clinical motor functions. Pathway enrichments from single cell‐RNA sequencing and proteomic analyses from sargramostim‐treated PD patients demonstrate a neuroprotective signature, including, but not limited to, antioxidant, anti‐inflammatory, and autophagy genes and proteins (LRRK2, HMOX1, TLR2, TLR8, RELA, ATG7, and GABARAPL2). Conclusions This monocyte profile provides an “early” and unique biomarker strategy to track clinical immune‐based interventions, but requiring validation in larger case studies.
Keywords	Parkinson's disease ; GM‐CSF ; monocytes ; scRNA‐seq ; proteomics ; biomarkers ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: New role of phenothiazine derivatives as peripherally acting CB1 receptor antagonizing anti-obesity agents.

Sharma, Mayank Kumar / Machhi, Jatin / Murumkar, Prashant / Yadav, Mange Ram

Scientific reports

2018 Volume 8, Issue 1, Page(s) 1650

Abstract: Developing peripherally active cannabinoid 1 (CB1) receptor antagonists is a novel therapeutic approach for the management of obesity. An unusual phenothiazine scaffold containing CB1R antagonizing hit was identified by adopting virtual screening work ... ...

Abstract	Developing peripherally active cannabinoid 1 (CB1) receptor antagonists is a novel therapeutic approach for the management of obesity. An unusual phenothiazine scaffold containing CB1R antagonizing hit was identified by adopting virtual screening work flow. The hit so identified was further modified by introducing polar functional groups into it to enhance the polar surface area and decrease the hydrophobicity of the resulting molecules. CB1 receptor antagonistic activity for the designed compounds was computed by the previously established pharmacophore and three dimensional quantitative structure-activity relationship models. Docking studies of these designed compounds confirmed the existence of favourable interactions within the active site of the CB1 receptor. The designed compounds were synthesized and evaluated for their CB1 receptor antagonistic activity. Parallel artificial membrane permeability assay was performed to evaluate their potential to permeate into the central nervous system wherein it was observed that the compounds did not possess the propensity to cross the blood brain barrier and would be devoid of central nervous system side effects. In pharmacological evaluation, the synthesized compounds (23, 25, 27 and 34) showed significant decrease in food intake suggesting their potential application in the management of obesity through CB1 receptor antagonist activity.
MeSH term(s)	Animals ; Anti-Obesity Agents/administration & dosage ; Anti-Obesity Agents/chemical synthesis ; Anti-Obesity Agents/pharmacology ; Feeding Behavior/drug effects ; Male ; Molecular Docking Simulation ; Phenothiazines/administration & dosage ; Phenothiazines/chemical synthesis ; Phenothiazines/pharmacology ; Protein Binding ; Quantitative Structure-Activity Relationship ; Rats, Wistar ; Receptor, Cannabinoid, CB1/antagonists & inhibitors
Chemical Substances	Anti-Obesity Agents ; Phenothiazines ; Receptor, Cannabinoid, CB1
Language	English
Publishing date	2018-01-26
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/s41598-018-20078-w
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Article ; Online: Harnessing regulatory T cell neuroprotective activities for treatment of neurodegenerative disorders.

Machhi, Jatin / Kevadiya, Bhavesh D / Muhammad, Ijaz Khan / Herskovitz, Jonathan / Olson, Katherine E / Mosley, R Lee / Gendelman, Howard E

Molecular neurodegeneration

2020 Volume 15, Issue 1, Page(s) 32

Abstract: Emerging evidence demonstrates that adaptive immunity influences the pathobiology of neurodegenerative disorders. Misfolded aggregated self-proteins can break immune tolerance leading to the induction of autoreactive effector T cells (Teffs) with ... ...

Abstract	Emerging evidence demonstrates that adaptive immunity influences the pathobiology of neurodegenerative disorders. Misfolded aggregated self-proteins can break immune tolerance leading to the induction of autoreactive effector T cells (Teffs) with associated decreases in anti-inflammatory neuroprotective regulatory T cells (Tregs). An imbalance between Teffs and Tregs leads to microglial activation, inflammation and neuronal injury. The cascade of such a disordered immunity includes the drainage of the aggregated protein antigens into cervical lymph nodes serving to amplify effector immune responses. Both preclinical and clinical studies demonstrate transformation of this altered immunity for therapeutic gain. We posit that the signs and symptoms of common neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and stroke can be attenuated by boosting Treg activities.
MeSH term(s)	Amyotrophic Lateral Sclerosis/immunology ; Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/therapy ; Animals ; Humans ; Inflammation/metabolism ; Neurodegenerative Diseases/immunology ; Neurodegenerative Diseases/therapy ; Neuroprotection ; Parkinson Disease/immunology ; Parkinson Disease/metabolism ; T-Lymphocytes, Regulatory/immunology
Language	English
Publishing date	2020-06-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2244557-2
ISSN	1750-1326 ; 1750-1326
ISSN (online)	1750-1326
ISSN	1750-1326
DOI	10.1186/s13024-020-00375-7
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Article ; Online: Development of an extended half-life GM-CSF fusion protein for Parkinson's disease.

Yeapuri, Pravin / Olson, Katherine E / Lu, Yaman / Abdelmoaty, Mai Mohamed / Namminga, Krista L / Markovic, Milica / Machhi, Jatin / Mosley, R Lee / Gendelman, Howard E

Journal of controlled release : official journal of the Controlled Release Society

2022 Volume 348, Page(s) 951–965

Abstract: Transformation of CD4+ T cell effector to regulatory (Teff to Treg) cells have been shown to attenuate disease progression by restoring immunological balance during the onset and progression of neurodegenerative diseases. In our prior studies, we defined ...

Abstract	Transformation of CD4+ T cell effector to regulatory (Teff to Treg) cells have been shown to attenuate disease progression by restoring immunological balance during the onset and progression of neurodegenerative diseases. In our prior studies, we defined a safe and effective pathway to restore this balance by restoring Treg numbers and function through the daily administration of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). These studies were conducted as a proof-of-concept testing in Parkinson's disease (PD) preclinical models and early phase I clinical investigations. In both instances, they served to ameliorate disease associated signs and symptoms. However, despite the recorded efficacy, the cytokine's short half-life, low bioavailability, and injection site reactions proved to be limitations for any broader use. To overcome these limitations, mRNA lipid nanoparticles encoding an extended half-life albumin-GM-CSF fusion protein were developed for both mouse (Msa-GM-CSF) and rat (Rsa-GM-CSF). These formulations were tested for immunomodulatory and neuroprotective efficacy using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and human wild-type alpha-synuclein (αSyn) overexpression preclinical models of PD. A single dose of the extended half-life mouse and rat mRNA lipid nanoparticles generated measurable GM-CSF plasma cytokine levels up to four days. Increased Treg frequency and function were associated with a resting microglial phenotype, nigrostriatal neuroprotection, and restoration of brain tissue immune homeostasis. These findings were substantively beyond the recorded efficacy of daily recombinant wild-type GM-CSF with a recorded half-life of six hours. Mechanistic evaluation of neuropathological transcriptional profiles performed in the disease-affected nigral brain region demonstrated an upregulation of neuroprotective CREB and synaptogenesis signaling and neurovascular coupling pathways. These findings highlight the mRNA-encoded albumin GM-CSF fusion protein modification linked to improvements in therapeutic efficacy. The improvements achieved were associated with the medicine's increased bioavailability. Taken together, the data demonstrate that mRNA LNP encoding the extended half-life albumin-GM-CSF fusion protein can serve as a benchmark for PD immune-based therapeutics. This is especially notable for improving adherence of drug regimens in a disease-affected patient population with known tremors and gait abnormalities.
MeSH term(s)	Albumins ; Animals ; Cytokines ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use ; Half-Life ; Humans ; Liposomes ; Mice ; Nanoparticles ; Parkinson Disease/drug therapy ; Parkinson Disease/genetics ; RNA, Messenger ; Rats ; Recombinant Proteins
Chemical Substances	Albumins ; Cytokines ; Lipid Nanoparticles ; Liposomes ; RNA, Messenger ; Recombinant Proteins ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
Language	English
Publishing date	2022-06-30
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2022.06.024
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Article ; Online: Immunotherapy for Parkinson's disease.

Schwab, Aaron D / Thurston, Mackenzie J / Machhi, Jatin / Olson, Katherine E / Namminga, Krista L / Gendelman, Howard E / Mosley, R Lee

Neurobiology of disease

2020 Volume 137, Page(s) 104760

Abstract: With the increasing prevalence of Parkinson's disease (PD), there is an immediate need to interdict disease signs and symptoms. In recent years this need was met through therapeutic approaches focused on regenerative stem cell replacement and alpha- ... ...

Abstract	With the increasing prevalence of Parkinson's disease (PD), there is an immediate need to interdict disease signs and symptoms. In recent years this need was met through therapeutic approaches focused on regenerative stem cell replacement and alpha-synuclein clearance. However, neither have shown long-term clinical benefit. A novel therapeutic approach designed to affect disease is focused on transforming the brain's immune microenvironment. As disordered innate and adaptive immune functions are primary components of neurodegenerative disease pathogenesis, this has emerged as a clear opportunity for therapeutic development. Interventions that immunologically restore the brain's homeostatic environment can lead to neuroprotective outcomes. These have recently been demonstrated in both laboratory and early clinical investigations. To these ends, efforts to increase the numbers and function of regulatory T cells over dominant effector cells that exacerbate systemic inflammation and neurodegeneration have emerged as a primary research focus. These therapeutics show broad promise in affecting disease outcomes beyond PD, such as for Alzheimer's disease, stroke and traumatic brain injuries, which share common neurodegenerative disease processes.
MeSH term(s)	Alzheimer Disease/immunology ; Alzheimer Disease/therapy ; Animals ; Humans ; Immunologic Factors/immunology ; Immunotherapy ; Inflammation/immunology ; Inflammation/therapy ; Parkinson Disease/immunology ; Parkinson Disease/pathology ; Parkinson Disease/therapy ; alpha-Synuclein/metabolism
Chemical Substances	Immunologic Factors ; alpha-Synuclein
Language	English
Publishing date	2020-01-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1211786-9
ISSN	1095-953X ; 0969-9961
ISSN (online)	1095-953X
ISSN	0969-9961
DOI	10.1016/j.nbd.2020.104760
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Article: Development of an extended half-life GM-CSF fusion protein for Parkinson's disease

Yeapuri, Pravin / Olson, Katherine E. / Lu, Yaman / Abdelmoaty, Mai Mohamed / Namminga, Krista L. / Markovic, Milica / Machhi, Jatin / Mosley, R. Lee / Gendelman, Howard E.

Journal of controlled release. 2022 June 10,

2022

Abstract	Transformation of CD4+ T cell effector to regulatory (Teff to Treg) cells have been shown to attenuate disease progression by restoring immunological balance during the onset and progression of neurodegenerative diseases. In our prior studies, we defined a safe and effective pathway to restore this balance by restoring Treg numbers and function through the daily administration of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). These studies were conducted as a proof-of-concept testing in Parkinson's disease (PD) preclinical models and early phase I clinical investigations. In both instances they served to ameliorate disease associated signs and symptoms. However, despite the recorded efficacy, the cytokine's short half-life, low bioavailability, and injection site reactions proved to be limitations for any broader use. To overcome these limitations, mRNA lipid nanoparticles encoding an extended half-life albumin-GM-CSF fusion protein were developed for both mouse (Msa-GM-CSF) and rat (Rsa-GM-CSF). These formulations were tested for immunomodulatory and neuroprotective efficacy using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and human wild-type alpha-synuclein (αSyn) overexpression preclinical models of PD. A single dose of the extended half-life mouse and rat mRNA lipid nanoparticles generated measurable GM-CSF plasma cytokine levels up to four days. Increased Treg frequency and function were associated with a resting microglial phenotype, nigrostriatal neuroprotection, and restoration of brain tissue immune homeostasis. These findings were substantively beyond the recorded efficacy of daily recombinant wild-type GM-CSF with a recorded half-life of six hours. Mechanistic evaluation of neuropathological transcriptional profiles performed in the disease-affected nigral brain region demonstrated an upregulation of neuroprotective CREB and synaptogenesis signaling and neurovascular coupling pathways. These findings highlight the mRNA-encoded albumin GM-CSF fusion protein modification linked to improvements in therapeutic efficacy. The improvements achieved were associated with the medicine's increased bioavailability. Taken together, the data demonstrate that mRNA LNP encoding the extended half-life albumin-GM-CSF fusion protein can serve as a benchmark for PD immune-based therapeutics. This is especially notable for improving adherence of drug regimens in a disease-affected patient population with known tremors and gait abnormalities.
Keywords	CD4-positive T-lymphocytes ; Parkinson disease ; albumins ; bioavailability ; brain ; disease progression ; drugs ; gait ; granulocyte-macrophage colony-stimulating factor ; half life ; homeostasis ; humans ; injection site ; lipids ; medicine ; mice ; neuroprotective effect ; patients ; phenotype ; rats ; synaptogenesis ; therapeutics ; transcription (genetics)
Language	English
Dates of publication	2022-0610
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2022.06.024
Database	NAL-Catalogue (AGRICOLA)

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