167 results on '"Cameron MJ"'
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2. Relationships and interactions between temperate reef fish communities, physical habitat structure and marine protection
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Cameron, MJ
- Abstract
Habitat heterogeneity and complexity are important factors responsible for structuring the associated faunal and algal compositions of temperate marine communities. Despite the efforts of traditional management approaches, the continued worldwide decline in commercial fisheries has led to a growing awareness and appreciation of ecosystem-based approaches as a potential means to sustainably managing and conserving the biodiversity of the World's oceans. Such an approach requires knowledge of the relevant environmental parameters, resources and habitats at multiple scales that are important in shaping the spatial distributions and abundances of marine communities. The magnitude of sampling effort required to sufficiently quantify marine biodiversity across whole ecosystems is generally prohibitive at broad management scales which has led to the need for more time and cost effective surrogate approaches utilising physical habitat data. Disentangling the separate importance of natural spatial and temporal habitat variability effects from those of spatial marine planning efforts is vital to ensuring successful management outcomes. To achieve this, scientists and managers first need to understand how specific aspects of the physical environment structure temperate reef-fish communities and at which scales they become relevant. The current availability of this information is limited across temperate marine environments of Southern Australia and Tasmania. This thesis investigates patterns in the community structure responses of temperate reef fish communities along the South Australian and Tasmanian coasts in response to aspects of their surrounding habitat structure. The first and second chapters of this thesis investigate how fish community structure varies in response to variability in the physical characteristics, heterogeneity and complexity of reef habitat; and how these responses in fish community assemblage structure vary with the spatial scale at which they are measured. Across large, inter-bioregional scales it is principally climatic and biogeographical differences between varying geographic positions which are important in structuring much of the temperate reef fish community structure around Australia, while at smaller, intra-bioregional and local scales, the importance of ecologically proximal physical variables, such as exposure, biogenic cover, refuge space and habitat substratum begin to come into effect suggesting an increasing importance of physical habitat heterogeneity and complexity towards finer ends of the scales investigated. The third chapter of this thesis investigates the potential of remotely sensed measures of habitat complexity (i.e. multibeam sonar derivative products) as surrogates to understanding how reef-fish community structure responds to the surrounding habitat. The bathymetry derived measures of habitat structure that were investigated were limited predictors of temperate reef fish community structure at fine resolutions with the most important variables identified being those acting as proxies of the predominant swell exposure. The final chapter attempts to disentangle the effects of natural community responses of reef-fish communities to their habitat structure from those related directly to marine protection. The results were largely uninformative but highlight the need for larger scale studies considering additional factors such as local anthropogenic pressure and recruitment variability in order to adequately apply this analysis approach across Tasmanian MPAs and maximise the ability to detect reserve effects. Overall, this thesis provides an improved understanding of the importance of physical structure in determining rocky reef marine assemblages and highlights some of the potential physical surrogate measures which should and should not be applied to predict spatial variability driven by such structure for use in all forms on marine spatial management.
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- 2023
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3. Habitat fragmentation causes collapse of kelp recruitment
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Layton, C, primary, Cameron, MJ, additional, Tatsumi, M, additional, Shelamoff, V, additional, Wright, JT, additional, and Johnson, CR, additional
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- 2020
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4. Patch size and density of canopy-forming kelp modify influences of ecosystem engineering on understorey algal and sessile invertebrate assemblages
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Shelamoff, V, primary, Layton, C, additional, Tatsumi, M, additional, Cameron, MJ, additional, Wright, JT, additional, and Johnson, CR, additional
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- 2019
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5. Proinflammatory gene expression profiles and severity of disease course in SARS patients
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Xu, L, Ran, L, Cameron, MJ, Persad, D, Danesh, A, Gold, W, Keshavjee, S, Brunton, J, Loeb, M, Kelvin, DJ, and the Canadian SARS Research Network
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ddc: 610 - Published
- 2004
6. Immune responses in patients with SARS: Lessons from cytokine and gene expression profiling, FACS analysis and epitope mapping
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Cameron, MJ, Xu, L, Ran, L, Cameron, C, Persad, D, Danesh, A, Gold, W, Keshavjee, S, Brunton, J, Loeb, M, Kelvin, DJ, and Canadian SARS Research Network (CSRN)
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ddc: 610 - Published
- 2004
7. Understanding community-habitat associations of temperate reef fishes using fine-resolution bathymetric measures of physical structure
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Cameron, MJ, primary, Lucieer, V, additional, Barrett, NS, additional, Johnson, CR, additional, and Edgar, GJ, additional
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- 2014
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8. PPO.41 Determining Adverse Events in UK Perinatal Care using The Institute for Healthcare Improvement Perinatal Trigger Tool
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Cameron, MJ, primary, Richardson, S, additional, and Kempenaar, M, additional
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- 2014
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9. PFM.30 Should placental histology be abandoned in times of national financial austerity?
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Partridge, GC, primary, Girling, A, additional, and Cameron, MJ, additional
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- 2014
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10. Behavioral medicine treatment of ruminative vomiting and associated weight loss in an adolescent with autism.
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Luiselli JK, Medeiros J, Jasinowski C, Smith A, and Cameron MJ
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Treated persistent ruminative vomiting of a 15-year-old boy with autism using a multicomponent behavioral medicine program within a residential facility. Preceding intervention the boy had lost 15 pounds associated with high-rate ruminating. The treatment program included a combination of dietary, nutritional, and behavioral procedures that emphasized food restrictions, satiation, and setting condition manipulations. Ruminative vomiting was reduced to near-zero levels and weight gain was achieved following treatment implementation. These therapeutic gains were sustained during a maintenance programming phase and at 1- through 4-month follow-up assessments. Issues related to functional assessment and treatment formulation in behavioral medicine intervention for ruminative vomiting are discussed. [ABSTRACT FROM AUTHOR]
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- 1994
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11. Optical Positions of Bright Galaxies South of +200 Declination
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Glanfield, JR, primary and Cameron, MJ, additional
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- 1967
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12. Sex-dependent niche responses modulate steady-state and regenerative hematopoiesis.
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Chaudhary R, Smith JNP, Tiwari R, Klein BR, Cordova BA, Petroze F, Richardson B, Broncano AV, Lee J, Parthasarathy PB, De Carvalho KIL, Cameron SJ, Lathia JD, Goodman WA, Cameron MJ, and Desai AB
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- Animals, Male, Female, Mice, Stem Cell Niche, Sex Characteristics, Hematopoietic Stem Cells metabolism, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cell Transplantation, Regeneration, Mice, Inbred C57BL, Transcriptome, Chemokine CXCL12 metabolism, Chemokine CXCL12 genetics, Hematopoiesis
- Abstract
Hematopoietic stem cells (HSCs) adapt to organismal blood production needs by balancing self-renewal and differentiation, adjusting to physiological demands and external stimuli. Although sex differences have been implicated in differential hematopoietic function in males versus females, the mediators responsible for these effects require further study. Here, we characterized hematopoiesis at a steady state and during regeneration following hematopoietic stem cell transplantation (HST). RNA sequencing of lineage(-) bone marrow cells from C57/Bl6 mice revealed a broad transcriptional similarity between the sexes. However, we identified distinct sex differences in key biological pathways, with female cells showing reduced expression of signatures involved in inflammation and enrichment of genes related to glycolysis, hypoxia, and cell cycle regulation, suggesting a more quiescent and less inflammatory profile compared with male cells. To determine the functional impacts of the observed transcriptomic differences, we performed sex-matched and mismatched transplantation studies of lineage(-) donor cells. During short-term 56-day HST recovery, we found a male donor cell proliferative advantage, coinciding with elevated serum TNF-α, and a male recipient engraftment advantage, coinciding with increased serum CXCL12. Together, we show that sex-specific cell responses, marked by differing expression of pathways regulating metabolism, hypoxia, and inflammation, shape normal and regenerative hematopoiesis, with implications for the clinical understanding of hematopoietic function., Competing Interests: Conflict of Interest Disclosure The authors have no conflicts of interest to declare., (Copyright © 2024 International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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13. Superficial parasternal intercostal plane blocks in cardiac surgery: a systematic review and meta-analysis.
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Cameron MJ, Long J, Kardash K, and Yang SS
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- Humans, Sternotomy methods, Sternotomy adverse effects, Analgesics, Opioid administration & dosage, Nerve Block methods, Pain, Postoperative prevention & control, Pain, Postoperative drug therapy, Cardiac Surgical Procedures methods, Intercostal Nerves drug effects, Randomized Controlled Trials as Topic
- Abstract
Purpose: Traditional multimodal analgesic strategies have several contraindications in cardiac surgery patients, forcing clinicians to use alternative options. Superficial parasternal intercostal plane blocks, anesthetizing the anterior cutaneous branches of the thoracic intercostal nerves, are being explored as a straightforward method to treat pain after sternotomy. We sought to evaluate the literature on the effects of superficial parasternal blocks on pain control after cardiac surgery., Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched MEDLINE, Embase, CENTRAL, and Web of Science databases for RCTs evaluating superficial parasternal intercostal plane blocks in adult patients undergoing cardiac surgery via midline sternotomy published from inception to 11 March 2022. The prespecified primary outcome was opioid consumption at 12 hr. The risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool, and the quality of evidence was evaluated using the grading of recommendations, assessments, development, and evaluations. Outcomes were analyzed with a random-effects model. All subgroups were prespecified., Results: We reviewed 1,275 citations. Eleven RCTs, comprising 756 patients, fulfilled the inclusion criteria. Only one study reported the prespecified primary outcome, precluding the possibility of meta-analysis. This study reported a reduction in opioid consumption (-11.2 mg iv morphine equivalents; 95% confidence interval [CI], -8.2 to -14.1) There was a reduction in opioid consumption at 24 hr (-7.2 mg iv morphine equivalents; 95% CI, -5.6 to -8.7; five trials; 436 participants; moderate certainty evidence). All five studies measuring complications reported that none were detected, which included a sample of 196 blocks., Conclusion: The literature suggests a potential benefit of using superficial parasternal blocks to improve acute postoperative pain control after cardiac surgery via midline sternotomy. Future studies specifying dosing regimens and adjuncts are required., Study Registration: PROSPERO (CRD42022306914); first submitted 22 March 2022., (© 2024. Canadian Anesthesiologists' Society.)
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- 2024
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14. Pre-vaccination transcriptomic profiles of immune responders to the MUC1 peptide vaccine for colon cancer prevention.
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Cameron CM, Raghu V, Richardson B, Zagore LL, Tamilselvan B, Golden J, Cartwright M, Schoen RE, Finn OJ, Benos PV, and Cameron MJ
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Self-antigens abnormally expressed on tumors, such as MUC1, have been targeted by therapeutic cancer vaccines. We recently assessed in two clinical trials in a preventative setting whether immunity induced with a MUC1 peptide vaccine could reduce high colon cancer risk in individuals with a history of premalignant colon adenomas. In both trials, there were immune responders and non-responders to the vaccine. Here we used PBMC pre-vaccination and 2 weeks after the first vaccine of responders and non-responders selected from both trials to identify early biomarkers of immune response involved in long-term memory generation and prevention of adenoma recurrence. We performed flow cytometry, phosflow, and differential gene expression analyses on PBMCs collected from MUC1 vaccine responders and non-responders pre-vaccination and two weeks after the first of three vaccine doses. MUC1 vaccine responders had higher frequencies of CD4 cells pre-vaccination, increased expression of CD40L on CD8 and CD4 T-cells, and a greater increase in ICOS expression on CD8 T-cells. Differential gene expression analysis revealed that iCOSL, PI3K AKT MTOR, and B-cell signaling pathways are activated early in response to the MUC1 vaccine. We identified six specific transcripts involved in elevated antigen presentation, B-cell activation, and NF-kB1 activation that were directly linked to finding antibody response at week 12. Finally, a model using these transcripts was able to predict non-responders with accuracy. These findings suggest that individuals who can be predicted to respond to the MUC1 vaccine, and potentially other vaccines, have greater readiness in all immune compartments to present and respond to antigens. Predictive biomarkers of MUC1 vaccine response may lead to more effective vaccines tailored to individuals with high risk for cancer but with varying immune fitness.
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- 2024
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15. Adjuvant AS01 activates human monocytes for costimulation and systemic inflammation.
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Smith CL, Richardson B, Rubsamen M, Cameron MJ, Cameron CM, and Canaday DH
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- Humans, Aged, Aged, 80 and over, Leukocytes, Mononuclear, Monocytes, Adjuvants, Immunologic pharmacology, Vaccines, Synthetic, Inflammation, Herpes Zoster prevention & control, Herpes Zoster Vaccine
- Abstract
Background: The adjuvanted recombinant zoster vaccine (RZV) is highly effective even in adults over 80 years old. The high efficacy of RZV is attributed to its highly reactogenic adjuvant, AS01, but limited studies have been done on AS01's activation of human immune cells., Methods: We stimulated peripheral blood mononuclear cells (PBMC) with AS01 and used flow cytometry and RNA Sequencing (RNAseq) to analyze the impacts on human primary cells., Results: We found that incubation of PBMC with AS01 activated monocytes to a greater extent than any other cell population, including dendritic cells. Both classical and non-classical monocytes demonstrated this activation. RNASeq showed that TNF-ɑ and IL1R pathways were highly upregulated in response to AS01 exposure, even in older adults., Conclusions: In a PBMC co-culture, AS01 strongly activates human monocytes to upregulate costimulation markers and induce cytokines that mediate systemic inflammation. Understanding AS01's impacts on human cells opens possibilities to further address the reduced vaccine response associated with aging., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David Canaday, Mark Cameron, Cheryl Cameron reports financial support was provided by National Institute of Allergy and Infectious Diseases. David Canaday reports financial support was provided by Veterans Health Administration., (Copyright © 2023. Published by Elsevier Ltd.)
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- 2024
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16. Simulated galactic cosmic ray exposure activates dose-dependent DNA repair response and down regulates glucosinolate pathways in arabidopsis seedlings.
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Dixit AR, Meyers AD, Richardson B, Richards JT, Richards SE, Neelam S, Levine HG, Cameron MJ, and Zhang Y
- Abstract
Outside the protection of Earth's magnetic field, organisms are constantly exposed to space radiation consisting of energetic protons and other heavier charged particles. With the goal of crewed Mars exploration, the production of fresh food during long duration space missions is critical for meeting astronauts' nutritional and psychological needs. However, the biological effects of space radiation on plants have not been sufficiently investigated and characterized. To that end, 10-day-old Arabidopsis seedlings were exposed to simulated Galactic Cosmic Rays (GCR) and assessed for transcriptomic changes. The simulated GCR irradiation was carried out in the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Lab (BNL). The exposures were conducted acutely for two dose points at 40 cGy or 80 cGy, with sequential delivery of proton, helium, oxygen, silicon, and iron ions. Control and irradiated seedlings were then harvested and preserved in RNAlater at 3 hrs post irradiation. Total RNA was isolated for transcriptomic analyses using RNAseq. The data revealed that the transcriptomic responses were dose-dependent, with significant upregulation of DNA repair pathways and downregulation of glucosinolate biosynthetic pathways. Glucosinolates are important for plant pathogen defense and for the taste of a plant, which are both relevant to growing plants for spaceflight. These findings fill in knowledge gaps of how plants respond to radiation in beyond-Earth environments., Competing Interests: AD and JR were employed by the company AETOS Systems Inc. under NASA LASSO II contract. SR was employed by the company Bionetics Corp. under NASA LASSO contract. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2023 Dixit, Meyers, Richardson, Richards, Richards, Neelam, Levine, Cameron and Zhang.)
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- 2023
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17. Loss of function of ribosomal protein L13a blocks blastocyst formation and reveals a potential nuclear role in gene expression.
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Kour R, Kim J, Roy A, Richardson B, Cameron MJ, Knott JG, and Mazumder B
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- Animals, Female, Humans, Mice, Pregnancy, Blastocyst, Chromatin Immunoprecipitation, Gene Expression, Embryonic Development genetics, Ribosomal Proteins genetics
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Ribosomal proteins play diverse roles in development and disease. Most ribosomal proteins have canonical roles in protein synthesis, while some exhibit extra-ribosomal functions. Previous studies in our laboratory revealed that ribosomal protein L13a (RPL13a) is involved in the translational silencing of a cohort of inflammatory proteins in myeloid cells. This prompted us to investigate the role of RPL13a in embryonic development. Here we report that RPL13a is required for early development in mice. Crosses between Rpl13a+/- mice resulted in no Rpl13a-/- offspring. Closer examination revealed that Rpl13a-/- embryos were arrested at the morula stage during preimplantation development. RNA sequencing analysis of Rpl13a-/- morulae revealed widespread alterations in gene expression, including but not limited to several genes encoding proteins involved in the inflammatory response, embryogenesis, oocyte maturation, stemness, and pluripotency. Ex vivo analysis revealed that RPL13a was localized to the cytoplasm and nucleus between the two-cell and morula stages. RNAi-mediated depletion of RPL13a phenocopied Rpl13a-/- embryos and knockdown embryos exhibited increased expression of IL-7 and IL-17 and decreased expression of the lineage specifier genes Sox2, Pou5f1, and Cdx2. Lastly, a protein-protein interaction assay revealed that RPL13a is associated with chromatin, suggesting an extra ribosomal function in transcription. In summary, our data demonstrate that RPL13a is essential for the completion of preimplantation embryo development. The mechanistic basis of the absence of RPL13a-mediated embryonic lethality will be addressed in the future through follow-up studies on ribosome biogenesis, global protein synthesis, and identification of RPL13a target genes using chromatin immunoprecipitation and RNA-immunoprecipitation-based sequencing., (© 2023 Federation of American Societies for Experimental Biology.)
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- 2023
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18. Activated NK Cells with Pro-inflammatory Features are Associated with Atherogenesis in Perinatally HIV-Acquired Adolescents.
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Alles M, Gunasena M, Kettelhut A, Ailstock K, Musiime V, Kityo C, Richardson B, Mulhern W, Tamilselvan B, Rubsamen M, Kasturiratna D, Demberg T, Cameron CM, Cameron MJ, Dirajlal-Fargo S, Funderburg NT, and Liyanage NPM
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Human immunodeficiency virus (HIV) is associated with persistent immune activation and dysfunction in people with HIV despite treatment with antiretroviral therapy (ART). Modulation of the immune system may be driven by: low-level HIV replication, co-pathogens, gut dysbiosis /translocation, altered lipid profiles, and ART toxicities. In addition, perinatally acquired HIV (PHIV) and lifelong ART may alter the development and function of the immune system. Our preliminary data and published literature suggest reprogramming innate immune cells may accelerate aging and increase the risk for future end-organ complications, including cardiovascular disease (CVD). The exact mechanisms, however, are currently unknown. Natural killer (NK) cells are a highly heterogeneous cell population with divergent functions. They play a critical role in HIV transmission and disease progression in adults. Recent studies suggest the important role of NK cells in CVDs; however, little is known about NK cells and their role in HIV-associated cardiovascular risk in PHIV adolescents. Here, we investigated NK cell subsets and their potential role in atherogenesis in PHIV adolescents compared to HIV-negative adolescents in Uganda. Our data suggest, for the first time, that activated NK subsets in PHIV adolescents may contribute to atherogenesis by promoting plasma oxidized low-density lipoprotein (Ox-LDL) uptake by vascular macrophages.
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- 2023
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19. IL-21-IgFc immunotherapy alters transcriptional landscape of lymph node cells leading to enhanced flu vaccine response in aging and SIV infection.
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Pallikkuth S, Kvistad D, Sirupangi T, Kizhner A, Pahwa R, Cameron MJ, Richardson B, Williams S, Ayupe A, Brooks M, Petrovas C, Villinger F, and Pahwa S
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- Humans, Animals, T-Lymphocytes, Helper-Inducer, Macaca mulatta, Lymph Nodes, Interleukins genetics, Vaccination, Influenza Vaccines, Simian Acquired Immunodeficiency Syndrome, Simian Immunodeficiency Virus physiology
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Aging people living with HIV (PWH) frequently manifest impaired antibody (Ab) responses to seasonal flu vaccination which has been attributed to ongoing inflammation and immune activation. We have recently reported a similar scenario in old simian immunodeficiency virus (SIV) infected rhesus macaques (RM) with controlled viremia and have been able to compensate for this deficiency by immunotherapy with interleukin (IL)-21-IgFc. To understand the underlying mechanisms of IL-21-induced immunomodulation leading to enhanced flu vaccine response in aging and SIV, we have investigated draining lymph node (LN) cells of IL-21-treated and -untreated animals at postvaccination. We observed IL-21-induced proliferation of flu-specific LN memory CD4 T cells, expansion of B cells expressing IL-21 receptor (IL-21R), and modest expansion of T follicular helper cells (Tfh) co-expressing T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and DNAX accessory molecule (DNAM-1). Transcriptional analysis of LN cells of IL-21-treated animals revealed significant inhibition of germinal center (GC) Tfh and B-cell interferon signaling pathways along with enhanced B-cell development and antigen presentation pathways. We conclude that IL-21 treatment at the time of flu vaccination in aging SIV-infected animals modulates the inductive LN GC activity, to reverse SIV-associated LN Tfh and B-cell dysfunction. IL-21 is a potential candidate molecule for immunotherapy to enhance flu vaccine responses in aging PWH who have deficient antibody responses., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
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- 2023
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20. A transcriptional evaluation of the melanoma and squamous cell carcinoma TIL compartment reveals an unexpected spectrum of exhausted and functional T cells.
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Cameron CM, Richardson B, Golden JB, Phoon YP, Tamilselvan B, Pfannenstiel L, Thapaliya S, Roversi G, Gao XH, Zagore LL, Cameron MJ, and Gastman BR
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Introduction: Significant heterogeneity exists within the tumor-infiltrating CD8 T cell population, and exhausted T cells harbor a subpopulation that may be replicating and may retain signatures of activation, with potential functional consequences in tumor progression. Dysfunctional immunity in the tumor microenvironment is associated with poor cancer outcomes, making exploration of these exhausted T cell subpopulations critical to the improvement of therapeutic approaches., Methods: To investigate mechanisms associated with terminally exhausted T cells, we sorted and performed transcriptional profiling of CD8
+ tumor-infiltrating lymphocytes (TILs) co-expressing the exhaustion markers PD-1 and TIM-3 from large-volume melanoma tumors. We additionally performed immunologic phenotyping and functional validation, including at the single-cell level, to identify potential mechanisms that underlie their dysfunctional phenotype., Results: We identified novel dysregulated pathways in CD8+ PD-1+ TIM-3+ cells that have not been well studied in TILs; these include bile acid and peroxisome pathway-related metabolism and mammalian target of rapamycin (mTOR) signaling pathways, which are highly correlated with immune checkpoint receptor expression., Discussion: Based on bioinformatic integration of immunophenotypic data and network analysis, we propose unexpected targets for therapies to rescue the immune response to tumors in melanoma., Competing Interests: BG is a consultant/advisory board member for Merck. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cameron, Richardson, Golden, Phoon, Tamilselvan, Pfannenstiel, Thapaliya, Roversi, Gao, Zagore, Cameron and Gastman.)- Published
- 2023
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21. Culture and Language Inclusion in the Practice of Applied Behavior Analysis: Next Steps for Improving Outcomes for Autistic Clients.
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Hernandez CD, Williams Awodeha NF, and Cameron MJ
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As applied behavior analysis (ABA) is widely prescribed as an intervention for autistic children, ABA practitioners must have a thorough understanding of the impact of language and culture on the individuals and families they serve. The twin purposes of this article are to discuss cultural humility in ASD service delivery, and to provide an overview of practice parameters for the expansion of equity and inclusion. These efforts are guided by the National Standards for Culturally and Linguistically Appropriate Services (CLAS) in Health and Health Care. Readers will be provided with recommendations for incorporating culturally and linguistically appropriate services into training, practice, and supervision in ABA settings., (© Association for Behavior Analysis International 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
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- 2023
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22. Upregulation of IFN-stimulated genes persists beyond the transitory broad immunologic changes of acute HIV-1 infection.
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Mackelprang RD, Filali-Mouhim A, Richardson B, Lefebvre F, Katabira E, Ronald A, Gray G, Cohen KW, Klatt NR, Pecor T, Celum C, McElrath MJ, Hughes SM, Hladik F, Cameron MJ, and Lingappa JR
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Chronic immune activation during HIV-1 infection contributes to morbidity and mortality in people living with HIV. To elucidate the underlying biological pathways, we evaluated whole blood gene expression trajectories from before, through acute, and into chronic HIV-1 infection. Interferon-stimulated genes, including MX1, IFI27 and ISG15, were upregulated during acute infection, remained elevated into chronic infection, and were strongly correlated with plasma HIV-1 RNA as well as TNF-α and CXCL10 cytokine levels. In contrast, genes involved in cellular immune responses, such as CD8A, were upregulated during acute infection before reaching a peak and returning to near pre-infection levels in chronic infection. Our results indicate that chronic immune activation during HIV-1 infection is characterized by persistent elevation of a narrow set of interferon-stimulated genes and innate cytokines. These findings raise the prospect of devising a targeted intervention to restore healthy immune homeostasis in people living with HIV-1., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)
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- 2023
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23. Upregulation of PTPRC and Interferon Response Pathways in HIV-1 Seroconverters Prior to Infection.
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Li Y, Lefebvre F, Nakku-Joloba E, Ronald A, Gray G, de Bruyn G, Kiarie J, Celum C, Cameron MJ, Lingappa JR, and Mackelprang RD
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- Humans, Interferons genetics, Up-Regulation, Leukocyte Common Antigens, HIV-1, HIV Infections
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Human immunodeficiency virus 1 (HIV-1) exposed seronegative (HESN) individuals may have unique characteristics that alter susceptibility to HIV-1 infection. However, identifying truly exposed HESN is challenging. We utilized stored data and biospecimens from HIV-1 serodifferent couple cohorts, in which couples' HIV-1 exposures were quantified based on unprotected sex frequency and viral load of the partner with HIV-1. We compared peripheral blood gene expression between 15 HESN and 18 seroconverters prior to infection. We found PTPRC (encoding CD45 antigen) and interferon-response pathways had significantly higher expression among individuals who went on to become seropositive and thus may be a signature for increased acquisition risk., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2023
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24. Differential CD4+ T-Cell Cytokine and Cytotoxic Responses Between Reactivation and Latent Phases of Herpes Zoster Infection.
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Jin W, Fang M, Sayin I, Smith C, Hunter JL, Richardson B, Golden JB, Haley C, Schmader KE, Betts MR, Tyring SK, Cameron CM, Cameron MJ, and Canaday DH
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Background: CD4+ T cells are a critical component of effective immune responses to varicella zoster virus (VZV), but their functional properties during the reactivation acute vs latent phase of infection remain poorly defined., Methods: Here we assessed the functional and transcriptomic properties of peripheral blood CD4+ T cells in persons with acute herpes zoster (HZ) compared to those with a prior history of HZ infection using multicolor flow cytometry and RNA sequencing., Results: We found significant differences between the polyfunctionality of VZV-specific total memory, effector memory, and central memory CD4+ T cells in acute vs prior HZ. VZV-specific CD4+ memory T-cell responses in acute HZ reactivation had higher frequencies of IFN-γ and IL-2 producing cells compared to those with prior HZ. In addition, cytotoxic markers were higher in VZV-specific CD4+ T cells than non-VZV-specific cells. Transcriptomic analysis of ex vivo total memory CD4+ T cells from these individuals showed differential regulation of T-cell survival and differentiation pathways, including TCR, cytotoxic T lymphocytes (CTL), T helper, inflammation, and MTOR signaling pathways. These gene signatures correlated with the frequency of IFN-γ and IL-2 producing cells responding to VZV., Conclusions: In summary, VZV-specific CD4+ T cells from acute HZ individuals had unique functional and transcriptomic features, and VZV-specific CD4+ T cells as a group had a higher expression of cytotoxic molecules including Perforin, Granzyme-B, and CD107a., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023 Pathogens and Immunity.)
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- 2023
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25. Significant Reduction in Vaccine-Induced Antibody Levels and Neutralization Activity Among Healthcare Workers and Nursing Home Residents 6 Months Following Coronavirus Disease 2019 BNT162b2 mRNA Vaccination.
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Canaday DH, Oyebanji OA, Keresztesy D, Payne M, Wilk D, Carias L, Aung H, St Denis K, Lam EC, Rowley CF, Berry SD, Cameron CM, Cameron MJ, Wilson BM, Balazs AB, King CL, and Gravenstein S
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- Antibodies, Neutralizing, Antibodies, Viral, BNT162 Vaccine, Health Personnel, Humans, Nursing Homes, RNA, Messenger, Vaccination, COVID-19 prevention & control, Influenza Vaccines
- Abstract
Antibody decline occurred from 2 weeks to 6 months post-BNT162b2 mRNA vaccination in nursing home (NH) residents and healthcare workers. Antispike, receptor-binding domain, and neutralization levels dropped >81% irrespective of prior infection. Notably, 69% of infection-naive NH residents had neutralizing antibodies at or below the assay's limit of detection., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)
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- 2022
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26. Pediatric Pain and Neurodevelopmental Disorders: Implications for Research and Practice in Behavior Analysis.
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McKeown CA, Vollmer TR, Cameron MJ, Kinsella L, and Shaibani S
- Abstract
Individuals diagnosed with a neurodevelopmental disorder also are commonly diagnosed with a medical comorbidity. Because of this, it is estimated that this population experiences nearly twice the incidence of pain or discomfort as their neurotypical peers. Although behavior analysts consider the effect of biological variables on a client's behavior, considerations of pain appear to be underdiscussed and understudied. The purpose of this article is to discuss how pain may interact with the efficacy of behavior analytic assessments and treatments, provide potential solutions to the barriers associated with pain states, and describe avenues to promote clinical research to improve our behavior analysis of pediatric pain while developing treatments for behavior problems such as aggression., Competing Interests: Conflict of Interests/Competing InterestsThe authors have no potential conflicts of interests to disclose., (© Association for Behavior Analysis International 2022.)
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- 2022
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27. Host transcriptomic signatures of tuberculosis can predict immune reconstitution inflammatory syndrome in HIV patients.
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Mbandi SK, Painter H, Penn-Nicholson A, Toefy A, Erasmus M, Hanekom WA, Scriba TJ, Lai RPJ, Marais S, Fletcher HA, Meintjes G, Wilkinson RJ, Cotton MF, Pahwa S, Cameron MJ, and Nemes E
- Subjects
- Adult, BCG Vaccine, Child, Humans, Transcriptome, HIV Infections complications, HIV Infections drug therapy, Immune Reconstitution Inflammatory Syndrome complications, Immune Reconstitution Inflammatory Syndrome diagnosis, Tuberculosis diagnosis
- Abstract
Immune reconstitution inflammatory syndrome (IRIS) can be a complication of antiretroviral therapy (ART) in patients with advanced HIV, but its pathogenesis is uncertain. In tuberculosis (TB) endemic countries, IRIS is often associated with mycobacterial infections or Bacille-Calmette-Guerin (BCG) vaccination in children. With no predictive or confirmatory tests at present, IRIS remains a diagnosis of exclusion. We tested whether RISK6 and Sweeney3, validated immune-based blood transcriptomic signatures for TB, could predict or diagnose IRIS in HIV+ children and adults. Transcripts were measured by RT-qPCR in BCG-vaccinated children and by microarray in HIV+ adults with TB including TB meningitis (TBM). Signature scores before ART initiation and up to IRIS diagnosis were compared between participants who did or did not develop IRIS. In children, RISK6 and Sweeney3 discriminated IRIS cases from non-IRIS controls before ART, and at diagnosis. In adults with TB, RISK6 discriminated IRIS cases from controls after half-week on ART and at TB-IRIS onset. In adults with TBM, only Sweeney3 discriminated IRIS cases from controls before ART, while both signatures distinguished cases from controls at TB-IRIS onset. Parsimonious whole blood transcriptomic signatures for TB showed potential to predict and diagnose IRIS in HIV+ children and adults., (© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)
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- 2022
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28. COVID-19 vaccine booster dose needed to achieve Omicron-specific neutralisation in nursing home residents.
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Canaday DH, Oyebanji OA, White E, Keresztesy D, Payne M, Wilk D, Carias L, Aung H, St Denis K, Sheehan ML, Berry SD, Cameron CM, Cameron MJ, Wilson BM, Balazs AB, King CL, and Gravenstein S
- Subjects
- Aged, Antibodies, Viral, BNT162 Vaccine, Humans, Immunization, Secondary, Middle Aged, Nursing Homes, SARS-CoV-2, Vaccines, Synthetic, mRNA Vaccines, COVID-19 prevention & control, COVID-19 Vaccines
- Abstract
Background: Nursing home (NH) residents have borne a disproportionate share of SARS-CoV-2 morbidity and mortality. Vaccines have limited hospitalisation and death from earlier variants in this vulnerable population. With the rise of Omicron and future variants, it is vital to sustain and broaden vaccine-induced protection. We examined the effect of boosting with BNT162b2 mRNA vaccine on humoral immunity and Omicron-specific neutralising activity among NH residents and healthcare workers (HCWs)., Methods: We longitudinally enrolled 85 NH residents (median age 77) and 48 HCWs (median age 51), and sampled them after the initial vaccination series; and just before and 2 weeks after booster vaccination. Anti-spike, anti-receptor binding domain (RBD) and neutralisation titres to the original Wuhan strain and neutralisation to the Omicron strain were obtained., Findings: Booster vaccination significantly increased vaccine-specific anti-spike, anti-RBD, and neutralisation levels above the pre-booster levels in NH residents and HCWs, both in those with and without prior SARS-CoV-2 infection. Omicron-specific neutralisation activity was low after the initial 2 dose series with only 28% of NH residents' and 28% HCWs' titres above the assay's lower limit of detection. Omicron neutralising activity following the booster lifted 86% of NH residents and 93% of HCWs to the detectable range., Interpretation: With boosting, the vast majority of HCWs and NH residents developed detectable Omicron-specific neutralising activity. These data provide immunologic evidence that strongly supports booster vaccination to broaden neutralising activity and counter waning immunity in the hope it will better protect this vulnerable, high-risk population against the Omicron variant., Funding: NIH AI129709-03S1, U01 CA260539-01, CDC 200-2016-91773, and VA BX005507-01., (Published by Elsevier B.V.)
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- 2022
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29. Density-dependence and seasonal variation in reproductive output and sporophyte production in the kelp, Ecklonia radiata.
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Tatsumi M, Mabin CJT, Layton C, Shelamoff V, Cameron MJ, Johnson CR, and Wright JT
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- Ecosystem, Reproduction, Seasons, Kelp, Phaeophyceae
- Abstract
The kelp, Ecklonia radiata, is an abundant subtidal ecosystem engineer in southern Australia. Density-dependent changes in the abiotic environment engineered by Ecklonia may feedback to affect reproduction and subsequent recruitment. Here, we examined: 1) how the reproductive capacity of Ecklonia individuals in the field (zoospores released · mm
-2 reproductive tissue) varied with adult density and time, and 2) how the recruitment of microscopic gametophytes and sporophytes was influenced by zoospore density at two times. Zoospore production did not vary with adult density, with only one month out of ten sampled over a 2-y period showing a significant effect of density. However, zoospore production varied hugely over time, being generally highest in mid-autumn and lowest in mid-late summer. There were strong effects of initial zoospore density on gametophyte and sporophyte recruitment with both a minimum and an optimum zoospore density for sporophyte recruitment, but these varied in time. Almost no sporophytes developed when initial zoospore density was <6.5 · mm-2 in spring or <0.5 · mm-2 in winter with optimum densities of 90-355 · mm-2 in spring and 21-261 · mm-2 in winter, which resulted in relatively high recruitment of 4-7 sporophytes · mm-2 . Sporophyte recruitment declined at initial zoospore densities >335 · mm-2 in spring and >261 · mm-2 in winter and was zero at very high zoospore densities. These findings suggest that although adult Ecklonia density does not affect per-capita zoospore production, because there is a minimum zoospore density for sporophyte production, a decline in population-level output could feedback to impact recruitment., (© 2021 Phycological Society of America.)- Published
- 2022
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30. Iron supplementation for patients undergoing cardiac surgery: a systematic review and meta-analysis of randomized controlled trials.
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Yang SS, Al Kharusi L, Gosselin A, Chirico A, Baradari PG, and Cameron MJ
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- Adult, Dietary Supplements, Humans, Iron therapeutic use, Randomized Controlled Trials as Topic, Anemia, Cardiac Surgical Procedures
- Abstract
Purpose: Iron supplementation has been evaluated in several randomized controlled trials (RCTs) for its potential to increase baseline hemoglobin and decrease red blood cell transfusion during cardiac surgery. This study's main objective was to evaluate the current evidence for iron administration in cardiac surgery patients., Methods: We searched MEDLINE, EMBASE, CENTRAL, Web of Science databases, and Google Scholar from inception to 19 November 2020 for RCTs evaluating perioperative iron administration in adult patients undergoing cardiac surgery. The RCTs were assessed using a risk of bias assessment and the quality of evidence was assessed using the grading of recommendations, assessments, development, and evaluations., Results: We reviewed 1,767 citations, and five studies (n = 554) met the inclusion criteria. The use of iron showed no statistical difference in incidence of transfusion (risk ratio, 0.86; 95% confidence interval, 0.65 to 1.13). Trial sequential analysis suggested an optimal information size of 1,132 participants, which the accrued information size did not reach., Conclusion: The current literature does not support or refute the routine use of iron therapy in cardiac surgery patients., Trial Registration: PROSPERO (CRD42020161927); registered 19 December 2019., (© 2021. Canadian Anesthesiologists' Society.)
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- 2022
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31. Significantly elevated antibody levels and neutralization titers in nursing home residents after SARS-CoV-2 BNT162b2 mRNA booster vaccination.
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Canaday DH, Oyebanji OA, White E, Keresztesy D, Payne M, Wilk D, Carias L, Aung H, St Denis K, Sheehan ML, Berry SD, Cameron CM, Cameron MJ, Wilson BM, Balazs AB, King CL, and Gravenstein S
- Abstract
Nursing home (NH) residents have experienced significant morbidity and mortality to SARS-CoV-2 throughout the pandemic. Vaccines initially curbed NH resident morbidity and mortality, but antibody levels and protection have declined with time since vaccination, prompting introduction of booster vaccination. This study assesses humoral immune response to booster vaccination in 85 NH residents and 44 health care workers (HCW) that we have followed longitudinally since initial SARS-CoV-2 BNT162b2 mRNA vaccination. The findings reveal that booster vaccination significantly increased anti-spike, anti-receptor binding domain, and neutralization titers above the pre-booster levels in almost all NH residents and HCW to significantly higher levels than shortly after the completion of the initial vaccine series. These data support the CDC recommendation to offer vaccine boosters to HCWs and NH residents on an immunological basis. Notably, even the older, more frail and more multi-morbid NH residents have sizable antibody increases with boosting.
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- 2021
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32. Reduced BNT162b2 Messenger RNA Vaccine Response in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Naive Nursing Home Residents.
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Canaday DH, Carias L, Oyebanji OA, Keresztesy D, Wilk D, Payne M, Aung H, St Denis K, Lam EC, Rowley CF, Berry SD, Cameron CM, Cameron MJ, Wilson B, Balazs AB, Gravenstein S, and King CL
- Subjects
- BNT162 Vaccine, COVID-19 Vaccines, Humans, Nursing Homes, RNA, Messenger, Vaccines, Synthetic, mRNA Vaccines, COVID-19, SARS-CoV-2
- Abstract
After BNT162b2 messenger RNA vaccination, antibody levels to spike, receptor-binding domain, and virus neutralization were examined in 149 nursing home residents and 110 healthcare worker controls. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-naive nursing home residents' median post-second vaccine dose antibody neutralization titers are one-quarter that of SARS-CoV-2-naive healthcare workers., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)
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- 2021
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33. Does a lack of vaccine side effects correlate with reduced BNT162b2 mRNA vaccine response among healthcare workers and nursing home residents?
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Oyebanji OA, Wilson B, Keresztesy D, Carias L, Wilk D, Payne M, Aung H, Denis KS, Lam EC, Rowley CF, Berry SD, Cameron CM, Cameron MJ, Schmader KE, Balazs AB, King CL, Canaday DH, and Gravenstein S
- Subjects
- BNT162 Vaccine, COVID-19 Vaccines, Health Personnel, Humans, Nursing Homes, RNA, Messenger genetics, SARS-CoV-2, COVID-19, Vaccines
- Abstract
Background: The BNT162b2 SARS-CoV-2 mRNA vaccination has mitigated the burden of COVID-19 among residents of long-term care facilities considerably, despite being excluded from the vaccine trials. Data on reactogenicity (vaccine side effects) in this population are limited., Aims: To assess reactogenicity among nursing home (NH) residents. To provide a plausible proxy for predicting vaccine response among this population., Methods: We enrolled and sampled NH residents and community-dwelling healthcare workers who received the BNT162b2 mRNA vaccine, to assess local or systemic reactogenicity and antibody levels (immunogenicity)., Results: NH residents reported reactions at a much lower frequency and lesser severity than the community-dwelling healthcare workers. These reactions were mild and transient with all subjects experiencing more local than systemic reactions. Based on our reactogenicity and immunogenicity data, we developed a linear regression model predicting log-transformed anti-spike, anti-receptor-binding domain (RBD), and neutralizing titers, with a dichotomous variable indicating the presence or absence of reported reactions which revealed a statistically significant effect, with estimated shifts in log-transformed titers ranging from 0.32 to 0.37 (all p < 0.01) indicating greater immunogenicity in subjects with one or more reported reactions of varying severity., Discussion: With a significantly lower incidence of post-vaccination reactions among NH residents as reported in this study, the BNT162b2 mRNA vaccine appears to be well-tolerated among this vulnerable population. If validated in larger populations, absence of reactogenicity could help guide clinicians in prioritizing vaccine boosters., Conclusions: Reactogenicity is significantly mild among nursing home residents and overall, subjects who reported post-vaccination reactions developed higher antibody titers., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)
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- 2021
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34. Interactive effects of canopy-driven changes in light, scour and water flow on microscopic recruits in kelp.
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Tatsumi M, Layton C, Cameron MJ, Shelamoff V, Johnson CR, and Wright JT
- Subjects
- Ecosystem, Forests, Water, Kelp, Phaeophyceae
- Abstract
Ecosystem engineering kelp forms habitat and influences associated communities by altering abiotic conditions. These conditions can also affect the engineer's own demographic rates but the mechanisms underpinning these feedbacks are not well known. Here, we tested the interactive effects of three abiotic factors engineered by the Australasian kelp Ecklonia radiata (light, water flow and scour) on the early survivorship and growth of its outplanted microscopic recruits. After six weeks, recruit survivorship was high in the absence of scour and low light (2-3 times higher than when scour was present) and under low water flow-ambient light conditions. Growth of sporophytes was strongly related to light, with recruits under ambient light approximately four times larger after six weeks. Overall, reduced scour (for survivorship) and ambient light (for growth) appear crucial for maximising E. radiata recruitment suggesting a healthy forest can provide microenvironments to enhance survivorship while gaps in the canopy enhance growth., (Copyright © 2021. Published by Elsevier Ltd.)
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- 2021
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35. Blastocyst Vitrification and Trophectoderm Biopsy Cumulatively Alter Embryonic Gene Expression in a Mouse Model.
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Van Heertum K, Lam L, Richardson B, Cartwright MJ, Mesiano SA, Cameron MJ, and Weinerman R
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- Animals, Blastocyst pathology, Cytoskeleton genetics, Cytoskeleton metabolism, Cytoskeleton pathology, Female, Mice, Pregnancy, Blastocyst metabolism, Embryo Culture Techniques methods, Embryo Transfer methods, Gene Expression Profiling methods, Transcription, Genetic physiology, Vitrification
- Abstract
Although embryo vitrification has been used extensively in human assisted reproductive technology (ART) and animal models, epidemiologic evidence and randomized controlled trials suggest differences in pregnancy/perinatal outcomes (birthweight, risk for preterm birth, and pre-eclampsia) between babies born from fresh versus frozen embryo transfers. To address the uncertainty surrounding the effects of laboratory manipulations of embryos on clinical outcomes, we subjected mouse blastocysts to increasing levels of manipulation for transcriptome analysis. Blastocysts were randomly divided into four groups: no manipulation (control), single vitrification/thaw (1 vit), double vitrification/thaw (2 vit), and single vitrification/thaw plus trophectoderm biopsy and again vitrified/thawed (2 vit + bx). Three sets of 15 blastocysts in each group were pooled for RNA sequencing, and differentially expressed genes (DEGs) and pathways were determined by statistical analysis. Blastocysts were also stained for ZO-1 and F-actin to assess cytoskeletal integrity. Freeze/thaw and biopsy manipulation affected multiple biological pathways. The most significant differences were detected in genes related to innate immunity, apoptosis, and mitochondrial function, with the magnitude of change proportional to the extent to manipulation. Significant disruptions were also seen in cytoskeletal staining, with greater disruptions seen with greater of manipulation. Our data suggests that embryo vitrification and biopsy affect embryo gene transcription, with several identified DEGs that may have plausible mechanisms for the clinical outcomes seen in human offspring following ART. Further study is required to determine whether these alterations in gene expression are associated with clinical differences seen in children born from fresh or frozen embryo transfer., (© 2021. Society for Reproductive Investigation.)
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- 2021
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36. Germinal Center T follicular helper (GC-Tfh) cell impairment in chronic HIV infection involves c-Maf signaling.
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Chakhtoura M, Fang M, Cubas R, O'Connor MH, Nichols CN, Richardson B, Talla A, Moir S, Cameron MJ, Tardif V, and Haddad EK
- Subjects
- Adult, Chronic Disease, Female, Germinal Center immunology, Humans, Male, Signal Transduction immunology, HIV Infections immunology, Proto-Oncogene Proteins c-maf immunology, T Follicular Helper Cells immunology
- Abstract
We have recently demonstrated that the function of T follicular helper (Tfh) cells from lymph nodes (LN) of HIV-infected individuals is impaired. We found that these cells were unable to provide proper help to germinal center (GC)-B cells, as observed by altered and inefficient anti-HIV antibody response and premature death of memory B cells. The underlying molecular mechanisms of this dysfunction remain poorly defined. Herein, we have used a unique transcriptional approach to identify these molecular defects. We consequently determined the transcriptional profiles of LN GC-Tfh cells following their interactions with LN GC-B cells from HIV-infected and HIV-uninfected individuals, rather than analyzing resting ex-vivo GC-Tfh cells. We observed that proliferating GC-Tfh cells from HIV-infected subjects were transcriptionally different than their HIV-uninfected counterparts, and displayed a significant downregulation of immune- and GC-Tfh-associated pathways and genes. Our results strongly demonstrated that MAF (coding for the transcription factor c-Maf) and its upstream signaling pathway mediators (IL6R and STAT3) were significantly downregulated in HIV-infected subjects, which could contribute to the impaired GC-Tfh and GC-B cell functions reported during infection. We further showed that c-Maf function was associated with the adenosine pathway and that the signaling upstream c-Maf could be partially restored by adenosine deaminase -1 (ADA-1) supplementation. Overall, we identified a novel mechanism that contributes to GC-Tfh cell impairment during HIV infection. Understanding how GC-Tfh cell function is altered in HIV is crucial and could provide critical information about the mechanisms leading to the development and maintenance of effective anti-HIV antibodies., Competing Interests: The authors have declared that no competing interests exist.
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- 2021
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37. Sex and age bias viral burden and interferon responses during SARS-CoV-2 infection in ferrets.
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Francis ME, Richardson B, Goncin U, McNeil M, Rioux M, Foley MK, Ge A, Pechous RD, Kindrachuk J, Cameron CM, Richardson C, Lew J, Machtaler S, Cameron MJ, Gerdts V, Falzarano D, and Kelvin AA
- Subjects
- Age Factors, Animals, Antibodies, Viral, COVID-19 metabolism, Disease Models, Animal, Female, Ferrets metabolism, Host Microbial Interactions, Interferons genetics, Male, SARS-CoV-2 isolation & purification, SARS-CoV-2 physiology, Sex Factors, Viral Load, Virus Replication, COVID-19 virology, Ferrets virology, Interferons metabolism
- Abstract
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and older ages. Here we investigated the impact of male sex and age comparing sex-matched or age-matched ferrets infected with SARS-CoV-2. Differences in temperature regulation was identified for male ferrets which was accompanied by prolonged viral replication in the upper respiratory tract after infection. Gene expression analysis of the nasal turbinates indicated that 1-year-old female ferrets had significant increases in interferon response genes post infection which were delayed in males. These results provide insight into COVID-19 and suggests that older males may play a role in viral transmission due to decreased antiviral responses., (© 2021. The Author(s).)
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- 2021
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38. Noninvasive prenatal screening in twin pregnancies with cell-free DNA using the IONA test: a prospective multicenter study.
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Khalil A, Archer R, Hutchinson V, Mousa HA, Johnstone ED, Cameron MJ, Cohen KE, Ioannou C, Kelly B, Reed K, Hulme R, and Papageorghiou AT
- Subjects
- Adult, Down Syndrome diagnosis, Female, Gestational Age, Humans, Infant, Newborn, Pregnancy, Prospective Studies, Sensitivity and Specificity, Trisomy 13 Syndrome diagnosis, Trisomy 18 Syndrome diagnosis, Cell-Free Nucleic Acids blood, Maternal Serum Screening Tests methods, Noninvasive Prenatal Testing methods, Pregnancy, Twin genetics
- Abstract
Background: In singleton pregnancies, studies investigating cell-free DNA in maternal blood have consistently reported high detection rate and low false-positive rate for the 3 common fetal trisomies (trisomies 21, 18, and 13). The potential advantages of noninvasive prenatal testing in twin pregnancies are even greater than in singletons, in particular lower need for invasive testing and consequent fetal loss rate. However, several organizations do not recommend cell-free DNA in twin pregnancies and call for larger prospective studies., Objective: In response to this, we undertook a large prospective multicenter study to establish the screening performance of cell-free DNA for the 3 common trisomies in twin pregnancies. Moreover, we combined our data with that reported in published studies to obtain the best estimate of screening performance., Study Design: This was a prospective multicenter blinded study evaluating the screening performance of cell-free DNA in maternal plasma for the detection of fetal trisomies in twin pregnancies. The study took place in 6 fetal medicine centers in England, United Kingdom. The primary outcome was the screening performance and test failure rate of cell-free DNA using next generation sequencing (the IONA test). Maternal blood was taken at the time of (or after) a conventional screening test. Data were collected at enrolment, at any relevant invasive testing throughout pregnancy, and after delivery until the time of hospital discharge. Prospective detailed outcome ascertainment was undertaken on all newborns. The study was undertaken and reported according to the Standards for Reporting of Diagnostic Accuracy Studies. A pooled analysis was also undertaken using our data and those in the studies identified by a literature search (MEDLINE, Embase, CENTRAL, Cochrane Library, and ClinicalTrials.gov) on June 6, 2020., Results: A total of 1003 women with twin pregnancies were recruited, and complete data with follow-up and reference data were available for 961 (95.8%); 276 were monochorionic and 685 were dichorionic. The failure rate was 0.31%. The mean fetal fraction was 12.2% (range, 3%-36%); all 9 samples with a 3% fetal fraction provided a valid result. There were no false-positive or false-negative results for trisomy 21 or trisomy 13, whereas there was 1 false-negative and 1 false-positive result for trisomy 18. The IONA test had a detection rate of 100% for trisomy 21 (n=13; 95% confidence interval, 75-100), 0% for trisomy 18 (n=1; 95% confidence interval, 0-98), and 100% for trisomy 13 (n=1; 95% confidence interval, 3-100). The corresponding false-positive rates were 0% (95% confidence interval, 0-0.39), 0.10% (95% confidence interval, 0-0.58), and 0% (95% confidence interval, 0-0.39), respectively. By combining data from our study with the 11 studies identified by literature search, the detection rate for trisomy 21 was 95% (n=74; 95% confidence interval, 90-99) and the false-positive rate was 0.09% (n=5598; 95% confidence interval, 0.03-0.19). The corresponding values for trisomy 18 were 82% (n=22; 95% confidence interval, 66-93) and 0.08% (n=4869; 95% confidence interval, 0.02-0.18), respectively. There were 5 cases of trisomy 13 and 3881 non-trisomy 13 pregnancies, resulting in a computed average detection rate of 80% and a false-positive rate of 0.13%., Conclusion: This large multicenter study confirms that cell-free DNA testing is the most accurate screening test for trisomy 21 in twin pregnancies, with screening performance similar to that in singletons and very low failure rates (0.31%). The predictive accuracy for trisomies 18 and 13 may be less. However, given the low false-positive rate, offering first-line screening with cell-free DNA to women with twin pregnancy is appropriate in our view and should be considered a primary screening test for trisomy 21 in twins., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2021
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39. Iron supplementation for patients undergoing cardiac surgery: a protocol for a systematic review and meta-analysis of randomized controlled trials.
- Author
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Cameron MJ, Al Kharusi L, Gosselin A, Baradari PG, Chirico A, Amar-Zifkin A, and Yang SS
- Subjects
- Hematinics pharmacology, Humans, Meta-Analysis as Topic, Research Design, Systematic Reviews as Topic, Cardiac Surgical Procedures methods, Iron Compounds pharmacology, Perioperative Care methods
- Abstract
Background: Iron administration has been evaluated in several randomized controlled trials for the potential of increasing baseline hemoglobin values and decreasing the incidence of red blood cell transfusion during cardiac surgery. We describe the protocol for a study aiming to evaluate the efficacy and safety of perioperative iron administration in patients undergoing cardiac surgery., Methods: We will search MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Web of Science, from inception to Nov. 19, 2020, for randomized controlled trials in any language evaluating the perioperative administration of iron in adult patients undergoing cardiac surgery; we will also include the first 50 results from Google Scholar. The primary outcome will be the incidence of red blood cell transfusion from the study intervention time until 8 weeks postoperatively. The secondary outcomes will be the number of red blood cell units transfused; change in ferritin level, reticulocyte count and hemoglobin concentration after iron administration; and adverse events. We will assess the risk of bias with the Cochrane Collaboration Risk of Bias Tool, and will analyze the primary and secondary outcomes using a random-effects model., Interpretation: This study will summarize the current evidence about perioperative iron administration in patients undergoing cardiac surgery, help determine whether this intervention should be included in enhanced-recovery protocols, and shape future research if needed. The final manuscript will be submitted to a peer-reviewed journal., Trial Registration: PROSPERO no. CRD42020161927., Competing Interests: Competing interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)
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- 2021
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40. Cell-free DNA in twin pregnancy: time to change screening recommendations.
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Papageorghiou AT, Hulme R, Khalil A, Archer R, Hutchinson V, Mousa HA, Johnstone ED, Cameron MJ, Cohen KE, Ioannou C, Kelly B, and Reed K
- Subjects
- Female, Humans, Pregnancy, Pregnancy, Twin, Trisomy, Cell-Free Nucleic Acids, Maternal Serum Screening Tests
- Published
- 2021
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41. A follicular regulatory Innate Lymphoid Cell population impairs interactions between germinal center Tfh and B cells.
- Author
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O'Connor MH, Muir R, Chakhtoura M, Fang M, Moysi E, Moir S, Carey AJ, Terk A, Nichols CN, Metcalf T, Petrovas C, Cameron MJ, Tardif V, and Haddad EK
- Subjects
- Adolescent, Adult, B-Lymphocytes immunology, Child, Child, Preschool, Female, Humans, Immunity, Innate immunology, Lymph Nodes immunology, Lymph Nodes metabolism, Lymphocyte Activation immunology, Lymphocytes metabolism, Male, Palatine Tonsil immunology, Palatine Tonsil metabolism, T Follicular Helper Cells immunology, Germinal Center immunology, Germinal Center physiology, Lymphocytes immunology
- Abstract
Innate Lymphoid Cells (ILCs) are immune cells typically found on mucosal surfaces and in secondary lymphoid organs where they regulate the immune response to pathogens. Despite their key role in the immune response, there are still fundamental gaps in our understanding of ILCs. Here we report a human ILC population present in the follicles of tonsils and lymph nodes termed follicular regulatory ILCs (ILC
FR ) that to our knowledge has not been previously identified. ILCFR have a distinct phenotype and transcriptional program when compared to other defined ILCs. Surprisingly, ILCFR inhibit the ability of follicular helper T (Tfh) cells to provide B cell help. The localization of ILCFR to the germinal centers suggests these cells may interfere with germinal center B cell (GC-B) and germinal center Tfh cell (GC-Tfh) interactions through the production of transforming growth factor beta (TGF-β. Intriguingly, under conditions of impaired GC-Tfh-GC-B cell interactions, such as human immunodeficiency virus (HIV) infection, the frequency of these cells is increased. Overall, we predict a role for ILCFR in regulating GC-Tfh-GC-B cell interactions and propose they expand in chronic inflammatory conditions.- Published
- 2021
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42. Transcriptional and Immunologic Correlates of Response to Pandemic Influenza Vaccine in Aviremic, HIV-Infected Children.
- Author
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de Armas LR, George V, Filali-Mouhim A, Steel C, Parmigiani A, Cunningham CK, Weinberg A, Trautmann L, Sekaly RP, Cameron MJ, and Pahwa S
- Subjects
- Adolescent, Adult, Antibodies, Viral immunology, Child, Child, Preschool, Female, Hemagglutination Inhibition Tests methods, Humans, Influenza A Virus, H1N1 Subtype immunology, Influenza, Human genetics, Influenza, Human immunology, Male, Receptors, CXCR5 immunology, T Follicular Helper Cells immunology, Vaccination methods, Young Adult, Antibody Formation genetics, Antibody Formation immunology, HIV Infections genetics, HIV Infections immunology, Influenza Vaccines immunology, Pandemics prevention & control, Transcription, Genetic genetics
- Abstract
People living with HIV (PWH) often exhibit poor responses to influenza vaccination despite effective combination anti-retroviral (ART) mediated viral suppression. There exists a paucity of data in identifying immune correlates of influenza vaccine response in context of HIV infection that would be useful in improving its efficacy in PWH, especially in younger individuals. Transcriptomic data were obtained by microarray from whole blood isolated from aviremic pediatric and adolescent HIV-infected individuals (4-25 yrs) given two doses of Novartis/H1N1 09 vaccine during the pandemic H1N1 influenza outbreak. Supervised clustering and gene set enrichment identified contrasts between individuals exhibiting high and low antibody responses to vaccination. High responders exhibited hemagglutination inhibition antibody titers >1:40 post-first dose and 4-fold increase over baseline. Baseline molecular profiles indicated increased gene expression in metabolic stress pathways in low responders compared to high responders. Inflammation-related and interferon-inducible gene expression pathways were higher in low responders 3 wks post-vaccination. The broad age range and developmental stage of participants in this study prompted additional analysis by age group (e.g. <13yrs and ≥13yrs). This analysis revealed differential enrichment of gene pathways before and after vaccination in the two age groups. Notably, CXCR5 , a homing marker expressed on T follicular helper (Tfh) cells, was enriched in high responders (>13yrs) following vaccination which was accompanied by peripheral Tfh expansion. Our results comprise a valuable resource of immune correlates of vaccine response to pandemic influenza in HIV infected children that may be used to identify favorable targets for improved vaccine design in different age groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 de Armas, George, Filali-Mouhim, Steel, Parmigiani, Cunningham, Weinberg, Trautmann, Sekaly, Cameron and Pahwa.)
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- 2021
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43. 15-PGDH inhibition activates the splenic niche to promote hematopoietic regeneration.
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Smith JN, Dawson DM, Christo KF, Jogasuria AP, Cameron MJ, Antczak MI, Ready JM, Gerson SL, Markowitz SD, and Desai AB
- Subjects
- Animals, Bone Marrow Cells cytology, Female, Gene Expression Profiling, Mice, Mice, Inbred C57BL, Spleen enzymology, Spleen metabolism, Bone Marrow Cells drug effects, Enzyme Inhibitors pharmacology, Hematopoiesis, Extramedullary drug effects, Hydroxyprostaglandin Dehydrogenases antagonists & inhibitors, Regeneration, Spleen drug effects
- Abstract
The splenic microenvironment regulates hematopoietic stem and progenitor cell (HSPC) function, particularly during demand-adapted hematopoiesis; however, practical strategies to enhance splenic support of transplanted HSPCs have proved elusive. We have previously demonstrated that inhibiting 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using the small molecule (+)SW033291 (PGDHi), increases BM prostaglandin E2 (PGE2) levels, expands HSPC numbers, and accelerates hematologic reconstitution after BM transplantation (BMT) in mice. Here we demonstrate that the splenic microenvironment, specifically 15-PGDH high-expressing macrophages, megakaryocytes (MKs), and mast cells (MCs), regulates steady-state hematopoiesis and potentiates recovery after BMT. Notably, PGDHi-induced neutrophil, platelet, and HSPC recovery were highly attenuated in splenectomized mice. PGDHi induced nonpathologic splenic extramedullary hematopoiesis at steady state, and pretransplant PGDHi enhanced the homing of transplanted cells to the spleen. 15-PGDH enzymatic activity localized specifically to macrophages, MK lineage cells, and MCs, identifying these cell types as likely coordinating the impact of PGDHi on splenic HSPCs. These findings suggest that 15-PGDH expression marks HSC niche cell types that regulate hematopoietic regeneration. Therefore, PGDHi provides a well-tolerated strategy to therapeutically target multiple HSC niches, promote hematopoietic regeneration, and improve clinical outcomes of BMT.
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- 2021
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44. Reduced BNT162b2 mRNA vaccine response in SARS-CoV-2-naive nursing home residents.
- Author
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Canaday DH, Carias L, Oyebanji OA, Keresztesy D, Wilk D, Payne M, Aung H, St Denis K, Lam EC, Wilson B, Rowley CF, Berry SD, Cameron CM, Cameron MJ, Balazs AB, Gravenstein S, and King CL
- Abstract
The SARS-CoV-2 pandemic impact on nursing home (NH) residents prompted their prioritization for early vaccination. To fill the data gap for vaccine immunogenicity in NH residents, we examined antibody levels after BNT162b2 mRNA vaccine to spike, receptor binding domain (RBD) and for virus neutralization in 149 NH residents and 111 health care worker controls. SARS-CoV-2-naive NH residents mount antibody responses with nearly 4-fold lower median neutralization titers and half the anti-spike level compared to SARS-CoV-2-naive healthcare workers. By contrast, SARS-CoV-2-recovered vaccinated NH residents had neutralization, anti-spike and anti-RBD titers similar to SARS-CoV-2-recovered vaccinated healthcare workers. NH residents' blunted antibody responses have important implications regarding the quality and durability of protection afforded by neoantigen vaccines. We urgently need better longitudinal evidence on vaccine effectiveness specific to NH resident populations to inform best practices for NH infection control measures, outbreak prevention and potential indication for a vaccine boost.
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- 2021
- Full Text
- View/download PDF
45. Levels of Soluble CD14 and Tumor Necrosis Factor Receptors 1 and 2 May Be Predictive of Death in Severe Coronavirus Disease 2019.
- Author
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Bowman ER, Cameron CMA, Avery A, Gabriel J, Kettelhut A, Hecker M, Sontich CU, Tamilselvan B, Nichols CN, Richardson B, Cartwright M, Funderburg NT, and Cameron MJ
- Subjects
- Biomarkers blood, COVID-19 blood, Cross-Sectional Studies, Humans, Longitudinal Studies, Predictive Value of Tests, Severity of Illness Index, COVID-19 mortality, Lipopolysaccharide Receptors blood, Receptors, Tumor Necrosis Factor, Type I blood, Receptors, Tumor Necrosis Factor, Type II blood
- Abstract
People infected with severe acute respiratory syndrome coronavirus 2 display a wide range of illness, from asymptomatic infection to severe respiratory distress resulting in death. We measured serum biomarkers in uninfected individuals and in individuals with mild, moderate, or critical coronavirus disease 2019 (COVID-19) disease. Levels of monocyte activation (soluble CD14 and fatty acid-binding protein 4) and inflammation (tumor necrosis factor receptors 1 and 2 [TNFR1 and TNFR2]) were increased in COVID-19 individuals, regardless of disease severity. Among patients with critical disease, individuals who recovered from COVID-19 had lower levels of TNFR1 and TNFR2 at hospital admission compared to these levels in patients with critical disease who ultimately died., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2021
- Full Text
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46. Monocytes as endogenous immune sensors: Identification of inflammatory, adhesion, and mTOR-related signatures in psoriasis.
- Author
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Golden JB, Richardson B, Seth D, Goldberg S, McCormick TS, Cooper KD, and Cameron MJ
- Subjects
- Cell Adhesion genetics, Cell Adhesion immunology, Gene Expression Regulation immunology, Humans, Monocytes metabolism, Psoriasis blood, Psoriasis pathology, RNA-Seq, Signal Transduction genetics, Signal Transduction immunology, TOR Serine-Threonine Kinases metabolism, Tacrolimus Binding Proteins genetics, Tacrolimus Binding Proteins metabolism, Monocytes immunology, Psoriasis immunology
- Abstract
Competing Interests: Declaration of Competing Interest KDC receives honoraria for consulting and serving on the advisory board for Novartis and Almirall. He is a principal investigator and receives funding from Pfizer (fellowship grant), Soligenix (sponsored study), and Celgene. All other authors have no conflict of interest to declare.
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- 2021
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47. Letter to the Editor: Prehabilitation Before Major Abdominal Surgery-A Systematic Review and Meta-Analysis.
- Author
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Chirico A, Cameron MJ, and Yang SS
- Subjects
- Humans, Preoperative Care, Abdomen surgery, Preoperative Exercise
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- 2021
- Full Text
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48. Development and deployment of COVID-19 vaccines for those most vulnerable.
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Koff WC, Schenkelberg T, Williams T, Baric RS, McDermott A, Cameron CM, Cameron MJ, Friemann MB, Neumann G, Kawaoka Y, Kelvin AA, Ross TM, Schultz-Cherry S, Mastro TD, Priddy FH, Moore KA, Ostrowsky JT, Osterholm MT, and Goudsmit J
- Subjects
- Animals, COVID-19 Vaccines adverse effects, Disease Models, Animal, Humans, Phylogeny, COVID-19 immunology, COVID-19 virology, COVID-19 Vaccines immunology, Disease Susceptibility, SARS-CoV-2 physiology
- Abstract
Development of safe and effective COVID-19 vaccines is a global priority and the best hope for ending the COVID-19 pandemic. Remarkably, in less than 1 year, vaccines have been developed and shown to be efficacious and are already being deployed worldwide. Yet, many challenges remain. Immune senescence and comorbidities in aging populations and immune dysregulation in populations living in low-resource settings may impede vaccine effectiveness. Distribution of vaccines among these populations where vaccine access is historically low remains challenging. In this Review, we address these challenges and provide strategies for ensuring that vaccines are developed and deployed for those most vulnerable., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
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- 2021
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49. Male sex and age biases viral burden, viral shedding, and type 1 and 2 interferon responses during SARS-CoV-2 infection in ferrets.
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Francis ME, Richardson B, McNeil M, Rioux M, Foley MK, Ge A, Pechous RD, Kindrachuk J, Cameron CM, Richardson C, Lew J, Cameron MJ, Gerdts V, Falzarano D, and Kelvin AA
- Abstract
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and the elderly. Here we investigated the impact of male sex and age by infecting adult male, aged male, and adult female ferrets with SARS-CoV-2. Aged male ferrets had a decrease in temperature which was accompanied by prolonged viral replication with increased pathology in the upper respiratory tract after infection. Transcriptome analysis of the nasal turbinates and lungs indicated that female ferrets had significant increases in interferon response genes (OASL, MX1, ISG15, etc.) on day 2 post infection which was delayed in aged males. In addition, genes associated with taste and smell such as RTP1, CHGA, and CHGA1 at later time points were upregulated in males but not in females. These results provide insight into COVID-19 and suggests that older males may play a role in viral transmission due to decreased antiviral responses.
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- 2021
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50. Drug perturbation gene set enrichment analysis (dpGSEA): a new transcriptomic drug screening approach.
- Author
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Fang M, Richardson B, Cameron CM, Dazard JE, and Cameron MJ
- Subjects
- CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes metabolism, Cell Cycle drug effects, Cell Cycle genetics, Humans, Phenotype, Probability, Computational Biology, Drug Evaluation, Preclinical methods, Transcriptome drug effects
- Abstract
Background: In this study, we demonstrate that our modified Gene Set Enrichment Analysis (GSEA) method, drug perturbation GSEA (dpGSEA), can detect phenotypically relevant drug targets through a unique transcriptomic enrichment that emphasizes biological directionality of drug-derived gene sets., Results: We detail our dpGSEA method and show its effectiveness in detecting specific perturbation of drugs in independent public datasets by confirming fluvastatin, paclitaxel, and rosiglitazone perturbation in gastroenteropancreatic neuroendocrine tumor cells. In drug discovery experiments, we found that dpGSEA was able to detect phenotypically relevant drug targets in previously published differentially expressed genes of CD4+T regulatory cells from immune responders and non-responders to antiviral therapy in HIV-infected individuals, such as those involved with virion replication, cell cycle dysfunction, and mitochondrial dysfunction. dpGSEA is publicly available at https://github.com/sxf296/drug_targeting ., Conclusions: dpGSEA is an approach that uniquely enriches on drug-defined gene sets while considering directionality of gene modulation. We recommend dpGSEA as an exploratory tool to screen for possible drug targeting molecules.
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- 2021
- Full Text
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