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  1. Article ; Online: Impact of Limosilactobacillus fermentum probiotic treatment on gut microbiota composition in sahiwal calves with rotavirus diarrhea: A 16S metagenomic analysis study".

    Murtaza, Nadeem / Nawaz, Muhammad / Yaqub, Tahir / Mehmood, Asim Khalid

    BMC microbiology

    2024  Volume 24, Issue 1, Page(s) 114

    Abstract: Background: Diarrhea poses a major threat to bovine calves leading to mortality and economic losses. Among the causes of calf diarrhea, bovine rotavirus is a major etiological agent and may result in dysbiosis of gut microbiota. The current study was ... ...

    Abstract Background: Diarrhea poses a major threat to bovine calves leading to mortality and economic losses. Among the causes of calf diarrhea, bovine rotavirus is a major etiological agent and may result in dysbiosis of gut microbiota. The current study was designed to investigate the effect of probiotic Limosilactobacillus fermentum (Accession No.OR504458) on the microbial composition of rotavirus-infected calves using 16S metagenomic analysis technique. Screening of rotavirus infection in calves below one month of age was done through clinical signs and Reverse Transcriptase PCR. The healthy calves (n = 10) were taken as control while the infected calves (n = 10) before treatment was designated as diarrheal group were treated with Probiotic for 5 days. All the calves were screened for the presence of rotavirus infection on each day and fecal scoring was done to assess the fecal consistency. Infected calves after treatment were designated as recovered group. Fecal samples from healthy, recovered and diarrheal (infected calves before sampling) were processed for DNA extraction while four samples from each group were processed for 16S metagenomic analysis using Illumina sequencing technique and analyzed via QIIME 2.
    Results: The results show that Firmicutes were more abundant in the healthy and recovered group than in the diarrheal group. At the same time Proteobacteria was higher in abundance in the diarrheal group. Order Oscillospirales dominated healthy and recovered calves and Enterobacterials dominated the diarrheal group. Alpha diversity indices show that diversity indices based on richness were higher in the healthy group and lower in the diarrheal group while a mixed pattern of clustering between diarrheal and recovered groups samples in PCA plots based on beta diversity indices was observed.
    Conclusion: It is concluded that probiotic Limosilactobacillus Fermentum N-30 ameliorate the dysbiosis caused by rotavirus diarrhea and may be used to prevent diarrhea in pre-weaned calves after further exploration.
    MeSH term(s) Animals ; Cattle ; Rotavirus/genetics ; Rotavirus Infections/drug therapy ; Rotavirus Infections/veterinary ; Gastrointestinal Microbiome/genetics ; Limosilactobacillus fermentum ; Dysbiosis ; Diarrhea/drug therapy ; Diarrhea/veterinary ; Feces/microbiology ; Probiotics/therapeutic use ; Cattle Diseases/drug therapy ; Cattle Diseases/microbiology
    Language English
    Publishing date 2024-04-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041505-9
    ISSN 1471-2180 ; 1471-2180
    ISSN (online) 1471-2180
    ISSN 1471-2180
    DOI 10.1186/s12866-024-03254-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Emerging proteomic approaches to identify the underlying pathophysiology of neurodevelopmental and neurodegenerative disorders.

    Murtaza, Nadeem / Uy, Jarryll / Singh, Karun K

    Molecular autism

    2020  Volume 11, Issue 1, Page(s) 27

    Abstract: Proteomics is the large-scale study of the total protein content and their overall function within a cell through multiple facets of research. Advancements in proteomic methods have moved past the simple quantification of proteins to the identification ... ...

    Abstract Proteomics is the large-scale study of the total protein content and their overall function within a cell through multiple facets of research. Advancements in proteomic methods have moved past the simple quantification of proteins to the identification of post-translational modifications (PTMs) and the ability to probe interactions between these proteins, spatially and temporally. Increased sensitivity and resolution of mass spectrometers and sample preparation protocols have drastically reduced the large amount of cells required and the experimental variability that had previously hindered its use in studying human neurological disorders. Proteomics offers a new perspective to study the altered molecular pathways and networks that are associated with autism spectrum disorders (ASD). The differences between the transcriptome and proteome, combined with the various types of post-translation modifications that regulate protein function and localization, highlight a novel level of research that has not been appropriately investigated. In this review, we will discuss strategies using proteomics to study ASD and other neurological disorders, with a focus on how these approaches can be combined with induced pluripotent stem cell (iPSC) studies. Proteomic analysis of iPSC-derived neurons have already been used to measure changes in the proteome caused by patient mutations, analyze changes in PTMs that resulted in altered biological pathways, and identify potential biomarkers. Further advancements in both proteomic techniques and human iPSC differentiation protocols will continue to push the field towards better understanding ASD disease pathophysiology. Proteomics using iPSC-derived neurons from individuals with ASD offers a window for observing the altered proteome, which is necessary in the future development of therapeutics against specific targets.
    MeSH term(s) Animals ; Biomarkers/metabolism ; Brain/metabolism ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Neurodegenerative Diseases/metabolism ; Neurodevelopmental Disorders/metabolism ; Protein Interaction Maps ; Protein Processing, Post-Translational ; Proteomics/methods
    Chemical Substances Biomarkers
    Language English
    Publishing date 2020-04-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2540930-X
    ISSN 2040-2392 ; 2040-2392
    ISSN (online) 2040-2392
    ISSN 2040-2392
    DOI 10.1186/s13229-020-00334-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Disruption of the autism-associated gene

    Brown, Chad O / Uy, Jarryll A / Murtaza, Nadeem / Rosa, Elyse / Alfonso, Alexandria / Dave, Biren M / Kilpatrick, Savannah / Cheng, Annie A / White, Sean H / Scherer, Stephen W / Singh, Karun K

    Frontiers in cellular neuroscience

    2024  Volume 17, Page(s) 1239069

    Abstract: ... ...

    Abstract SCN2A
    Language English
    Publishing date 2024-01-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2023.1239069
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Purinergic Signalling Mediates Aberrant Excitability of Developing Neuronal Circuits in the Fmr1 Knockout Mouse Model.

    Reynolds, Kathryn E / Huang, Eileen / Sabbineni, Monica / Wiseman, Eliza / Murtaza, Nadeem / Ahuja, Desmond / Napier, Matt / Murphy, Kathryn M / Singh, Karun K / Scott, Angela L

    Molecular neurobiology

    2024  

    Abstract: Neuronal hyperexcitability within developing cortical circuits is a common characteristic of several heritable neurodevelopmental disorders, including Fragile X Syndrome (FXS), intellectual disability and autism spectrum disorders (ASD). While this ... ...

    Abstract Neuronal hyperexcitability within developing cortical circuits is a common characteristic of several heritable neurodevelopmental disorders, including Fragile X Syndrome (FXS), intellectual disability and autism spectrum disorders (ASD). While this aberrant circuitry is typically studied from a neuron-centric perspective, glial cells secrete soluble factors that regulate both neurite extension and synaptogenesis during development. The nucleotide-mediated purinergic signalling system is particularly instrumental in facilitating these effects. We recently reported that within a FXS animal model, the Fmr1 KO mouse, the purinergic signalling system is upregulated in cortical astrocytes leading to altered secretion of synaptogenic and plasticity-related proteins. In this study, we examined whether elevated astrocyte purinergic signalling also impacts neuronal morphology and connectivity of Fmr1 KO cortical neurons. Here, we found that conditioned media from primary Fmr1 KO astrocytes was sufficient to enhance neurite extension and complexity of both wildtype and Fmr1 KO neurons to a similar degree as UTP-mediated outgrowth. Significantly enhanced firing was also observed in Fmr1 KO neuron-astrocyte co-cultures grown on microelectrode arrays but was associated with large deficits in firing synchrony. The selective P2Y
    Language English
    Publishing date 2024-04-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645020-9
    ISSN 1559-1182 ; 0893-7648
    ISSN (online) 1559-1182
    ISSN 0893-7648
    DOI 10.1007/s12035-024-04181-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The autism susceptibility kinase, TAOK2, phosphorylates eEF2 and modulates translation.

    Henis, Melad / Rücker, Tabitha / Scharrenberg, Robin / Richter, Melanie / Baltussen, Lucas / Hong, Shuai / Meka, Durga Praveen / Schwanke, Birgit / Neelagandan, Nagammal / Daaboul, Danie / Murtaza, Nadeem / Krisp, Christoph / Harder, Sönke / Schlüter, Hartmut / Kneussel, Matthias / Hermans-Borgmeyer, Irm / de Wit, Joris / Singh, Karun K / Duncan, Kent E /
    de Anda, Froylan Calderón

    Science advances

    2024  Volume 10, Issue 15, Page(s) eadf7001

    Abstract: Genes implicated in translation control have been associated with autism spectrum disorders (ASDs). However, some important genetic causes of autism, including ... ...

    Abstract Genes implicated in translation control have been associated with autism spectrum disorders (ASDs). However, some important genetic causes of autism, including the
    MeSH term(s) Animals ; Mice ; Autistic Disorder/genetics ; Peptide Elongation Factor 2 ; Phosphorylation ; Autism Spectrum Disorder/genetics ; Biological Assay ; Ursidae
    Chemical Substances Peptide Elongation Factor 2
    Language English
    Publishing date 2024-04-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adf7001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Proteomic Analysis Reveals Autism-Associated Gene

    Kwan, Vickie / Rosa, Elyse / Xing, Sansi / Murtaza, Nadeem / Singh, Kanwaldeep / Holzapfel, Nicholas T / Berg, Tobias / Lu, Yu / Singh, Karun K

    Journal of proteome research

    2020  Volume 20, Issue 1, Page(s) 1052–1062

    Abstract: DIX-domain containing 1 (Dixdc1) is an important regulator of neuronal development including cortical neurogenesis, neuronal migration and synaptic connectivity, and sequence variants in the gene have been linked to autism spectrum disorders (ASDs). ... ...

    Abstract DIX-domain containing 1 (Dixdc1) is an important regulator of neuronal development including cortical neurogenesis, neuronal migration and synaptic connectivity, and sequence variants in the gene have been linked to autism spectrum disorders (ASDs). Previous studies indicate that Dixdc1 controls neurogenesis through Wnt signaling, whereas its regulation of dendrite and synapse development requires Wnt and cytoskeletal signaling. However, the prediction of these signaling pathways is primarily based on the structure of Dixdc1. Given the role of Dixdc1 in neural development and brain disorders, we hypothesized that Dixdc1 may regulate additional signaling pathways in the brain. We performed transcriptomic and proteomic analyses of
    MeSH term(s) Animals ; Autistic Disorder ; Cell Movement ; Intracellular Signaling Peptides and Proteins ; Mice ; Microfilament Proteins ; Proteomics
    Chemical Substances Dixdc1 protein, mouse ; Intracellular Signaling Peptides and Proteins ; Microfilament Proteins
    Language English
    Publishing date 2020-12-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.0c00896
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: TAOK2 rescues autism-linked developmental deficits in a 16p11.2 microdeletion mouse model.

    Scharrenberg, Robin / Richter, Melanie / Johanns, Ole / Meka, Durga Praveen / Rücker, Tabitha / Murtaza, Nadeem / Lindenmaier, Zsuzsa / Ellegood, Jacob / Naumann, Anne / Zhao, Bing / Schwanke, Birgit / Sedlacik, Jan / Fiehler, Jens / Hanganu-Opatz, Ileana L / Lerch, Jason P / Singh, Karun K / de Anda, Froylan Calderon

    Molecular psychiatry

    2022  Volume 27, Issue 11, Page(s) 4707–4721

    Abstract: The precise development of the neocortex is a prerequisite for higher cognitive and associative functions. Despite numerous advances that have been made in understanding neuronal differentiation and cortex development, our knowledge regarding the impact ... ...

    Abstract The precise development of the neocortex is a prerequisite for higher cognitive and associative functions. Despite numerous advances that have been made in understanding neuronal differentiation and cortex development, our knowledge regarding the impact of specific genes associated with neurodevelopmental disorders on these processes is still limited. Here, we show that Taok2, which is encoded in humans within the autism spectrum disorder (ASD) susceptibility locus 16p11.2, is essential for neuronal migration. Overexpression of de novo mutations or rare variants from ASD patients disrupts neuronal migration in an isoform-specific manner. The mutated TAOK2α variants but not the TAOK2β variants impaired neuronal migration. Moreover, the TAOK2α isoform colocalizes with microtubules. Consequently, neurons lacking Taok2 have unstable microtubules with reduced levels of acetylated tubulin and phosphorylated JNK1. Mice lacking Taok2 develop gross cortical and cortex layering abnormalities. Moreover, acute Taok2 downregulation or Taok2 knockout delayed the migration of upper-layer cortical neurons in mice, and the expression of a constitutively active form of JNK1 rescued these neuronal migration defects. Finally, we report that the brains of the Taok2 KO and 16p11.2 del Het mouse models show striking anatomical similarities and that the heterozygous 16p11.2 microdeletion mouse model displayed reduced levels of phosphorylated JNK1 and neuronal migration deficits, which were ameliorated upon the introduction of TAOK2α in cortical neurons and in the developing cortex of those mice. These results delineate the critical role of TAOK2 in cortical development and its contribution to neurodevelopmental disorders, including ASD.
    MeSH term(s) Animals ; Humans ; Mice ; Autism Spectrum Disorder/genetics ; Autistic Disorder/genetics ; Disease Models, Animal ; Microtubules/genetics ; Microtubules/metabolism ; Neocortex/metabolism ; Neurogenesis/genetics ; Neurogenesis/physiology ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism
    Chemical Substances Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Taok2 protein, mouse (EC 2.7.11.1) ; TAOK2 protein, human (EC 2.7.1.-)
    Language English
    Publishing date 2022-09-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 1330655-8
    ISSN 1476-5578 ; 1359-4184
    ISSN (online) 1476-5578
    ISSN 1359-4184
    DOI 10.1038/s41380-022-01785-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Impaired OTUD7A-dependent Ankyrin regulation mediates neuronal dysfunction in mouse and human models of the 15q13.3 microdeletion syndrome.

    Unda, Brianna K / Chalil, Leon / Yoon, Sehyoun / Kilpatrick, Savannah / Irwin, Courtney / Xing, Sansi / Murtaza, Nadeem / Cheng, Anran / Brown, Chad / Afonso, Alexandria / McCready, Elizabeth / Ronen, Gabriel M / Howe, Jennifer / Caye-Eude, Aurélie / Verloes, Alain / Doble, Brad W / Faivre, Laurence / Vitobello, Antonio / Scherer, Stephen W /
    Lu, Yu / Penzes, Peter / Singh, Karun K

    Molecular psychiatry

    2023  Volume 28, Issue 4, Page(s) 1747–1769

    Abstract: Copy number variations (CNVs) are associated with psychiatric and neurodevelopmental disorders (NDDs), and most, including the recurrent 15q13.3 microdeletion disorder, have unknown disease mechanisms. We used a heterozygous 15q13.3 microdeletion mouse ... ...

    Abstract Copy number variations (CNVs) are associated with psychiatric and neurodevelopmental disorders (NDDs), and most, including the recurrent 15q13.3 microdeletion disorder, have unknown disease mechanisms. We used a heterozygous 15q13.3 microdeletion mouse model and patient iPSC-derived neurons to reveal developmental defects in neuronal maturation and network activity. To identify the underlying molecular dysfunction, we developed a neuron-specific proximity-labeling proteomics (BioID2) pipeline, combined with patient mutations, to target the 15q13.3 CNV genetic driver OTUD7A. OTUD7A is an emerging independent NDD risk gene with no known function in the brain, but has putative deubiquitinase function. The OTUD7A protein-protein interaction network included synaptic, axonal, and cytoskeletal proteins and was enriched for ASD and epilepsy risk genes (Ank3, Ank2, SPTAN1, SPTBN1). The interactions between OTUD7A and Ankyrin-G (Ank3) and Ankyrin-B (Ank2) were disrupted by an epilepsy-associated OTUD7A L233F variant. Further investigation of Ankyrin-G in mouse and human 15q13.3 microdeletion and OTUD7A
    MeSH term(s) Humans ; Mice ; Animals ; Ankyrins/genetics ; DNA Copy Number Variations ; Epilepsy/genetics ; Neurons
    Chemical Substances Ankyrins
    Language English
    Publishing date 2023-01-06
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1330655-8
    ISSN 1476-5578 ; 1359-4184
    ISSN (online) 1476-5578
    ISSN 1359-4184
    DOI 10.1038/s41380-022-01937-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Neuron-specific protein network mapping of autism risk genes identifies shared biological mechanisms and disease-relevant pathologies.

    Murtaza, Nadeem / Cheng, Annie A / Brown, Chad O / Meka, Durga Praveen / Hong, Shuai / Uy, Jarryll A / El-Hajjar, Joelle / Pipko, Neta / Unda, Brianna K / Schwanke, Birgit / Xing, Sansi / Thiruvahindrapuram, Bhooma / Engchuan, Worrawat / Trost, Brett / Deneault, Eric / Calderon de Anda, Froylan / Doble, Bradley W / Ellis, James / Anagnostou, Evdokia /
    Bader, Gary D / Scherer, Stephen W / Lu, Yu / Singh, Karun K

    Cell reports

    2022  Volume 41, Issue 8, Page(s) 111678

    Abstract: There are hundreds of risk genes associated with autism spectrum disorder (ASD), but signaling networks at the protein level remain unexplored. We use neuron-specific proximity-labeling proteomics (BioID2) to identify protein-protein interaction (PPI) ... ...

    Abstract There are hundreds of risk genes associated with autism spectrum disorder (ASD), but signaling networks at the protein level remain unexplored. We use neuron-specific proximity-labeling proteomics (BioID2) to identify protein-protein interaction (PPI) networks for 41 ASD risk genes. Neuron-specific PPI networks, including synaptic transmission proteins, are disrupted by de novo missense variants. The PPI network map reveals convergent pathways, including mitochondrial/metabolic processes, Wnt signaling, and MAPK signaling. CRISPR knockout displays an association between mitochondrial activity and ASD risk genes. The PPI network shows an enrichment of 112 additional ASD risk genes and differentially expressed genes from postmortem ASD patients. Clustering of risk genes based on PPI networks identifies gene groups corresponding to clinical behavior score severity. Our data report that cell type-specific PPI networks can identify individual and convergent ASD signaling networks, provide a method to assess patient variants, and highlight biological insight into disease mechanisms and sub-cohorts of ASD.
    MeSH term(s) Humans ; Autistic Disorder/genetics ; Autism Spectrum Disorder/genetics ; Protein Interaction Maps/genetics ; Neurons ; Proteins ; Wnt Signaling Pathway
    Chemical Substances Proteins
    Language English
    Publishing date 2022-11-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2022.111678
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: CD70 as an actionable immunotherapeutic target in recurrent glioblastoma and its microenvironment.

    Seyfrid, Mathieu / Maich, William Thomas / Shaikh, Vaseem Muhammad / Tatari, Nazanin / Upreti, Deepak / Piyasena, Deween / Subapanditha, Minomi / Savage, Neil / McKenna, Dillon / Mikolajewicz, Nicholas / Han, Hong / Chokshi, Chirayu / Kuhlmann, Laura / Khoo, Amanda / Salim, Sabra Khalid / Archibong-Bassey, Blessing / Gwynne, William / Brown, Kevin / Murtaza, Nadeem /
    Bakhshinyan, David / Vora, Parvez / Venugopal, Chitra / Moffat, Jason / Kislinger, Thomas / Singh, Sheila

    Journal for immunotherapy of cancer

    2022  Volume 10, Issue 1

    Abstract: Purpose: Glioblastoma (GBM) patients suffer from a dismal prognosis, with standard of care therapy inevitably leading to therapy-resistant recurrent tumors. The presence of cancer stem cells (CSCs) drives the extensive heterogeneity seen in GBM, ... ...

    Abstract Purpose: Glioblastoma (GBM) patients suffer from a dismal prognosis, with standard of care therapy inevitably leading to therapy-resistant recurrent tumors. The presence of cancer stem cells (CSCs) drives the extensive heterogeneity seen in GBM, prompting the need for novel therapies specifically targeting this subset of tumor-driving cells. Here, we identify CD70 as a potential therapeutic target for recurrent GBM CSCs.
    Experimental design: In the current study, we identified the relevance and functional influence of CD70 on primary and recurrent GBM cells, and further define its function using established stem cell assays. We use CD70 knockdown studies, subsequent RNAseq pathway analysis, and
    Results: CD70 expression is elevated in recurrent GBM and CD70 knockdown reduces tumorigenicity
    Conclusion: CD70 plays a key role in recurrent GBM cell aggressiveness and maintenance. Immunotherapeutic targeting of CD70 significantly improves survival in animal models and the CD70/CD27 axis may be a viable polytherapeutic avenue to co-target both GBM and its TIME.
    MeSH term(s) Animals ; Brain Neoplasms/immunology ; Brain Neoplasms/therapy ; CD27 Ligand/metabolism ; Cell Proliferation ; Glioblastoma/immunology ; Glioblastoma/therapy ; Humans ; Immunotherapy/methods ; Male ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Recurrence, Local ; Prognosis ; Proteomics/methods ; Transcriptome/genetics ; Tumor Microenvironment/immunology ; Mice
    Chemical Substances CD27 Ligand
    Language English
    Publishing date 2022-01-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2021-003289
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