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Article ; Online: Rethinking the role of senior medical students in the COVID-19 response.

Wang, Jim H-S / Tan, Sarah / Raubenheimer, Kyle

2020 Volume 212, Issue 10, Page(s) 490–490.e1

MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus Infections/epidemiology ; Education, Medical, Undergraduate ; Humans ; Medical Staff, Hospital/education ; Pandemics ; Pneumonia, Viral/epidemiology ; Professional Role ; SARS-CoV-2 ; Students, Medical
Keywords	covid19
Language	English
Publishing date	2020-05-05
Publishing country	Australia
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	186082-3
ISSN	1326-5377 ; 0025-729X
ISSN (online)	1326-5377
ISSN	0025-729X
DOI	10.5694/mja2.50601
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Article: Rethinking the role of senior medical students in the COVID-19 response

Wang, Jim H-S / Tan, Sarah / Raubenheimer, Kyle

Med J Aust

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #175795
Database	COVID19

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Article ; Online: Rethinking the role of senior medical students in the COVID ‐19 response

Wang, Jim H‐S / Tan, Sarah / Raubenheimer, Kyle

Medical Journal of Australia

2020 Volume 212, Issue 10, Page(s) 490

Keywords	General Medicine ; covid19
Language	English
Publisher	AMPCo
Publishing country	au
Document type	Article ; Online
ZDB-ID	186082-3
ISSN	1326-5377 ; 0025-729X
ISSN (online)	1326-5377
ISSN	0025-729X
DOI	10.5694/mja2.50601
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Glycan degradation promotes macroautophagy.

Baudot, Alice D / Wang, Victoria M-Y / Leach, Josh D / O'Prey, Jim / Long, Jaclyn S / Paulus-Hock, Viola / Lilla, Sergio / Thomson, David M / Greenhorn, John / Ghaffar, Farah / Nixon, Colin / Helfrich, Miep H / Strathdee, Douglas / Pratt, Judith / Marchesi, Francesco / Zanivan, Sara / Ryan, Kevin M

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 26, Page(s) e2111506119

Abstract: Macroautophagy promotes cellular homeostasis by delivering cytoplasmic constituents to lysosomes for degradation [Mizushima, ...

Abstract	Macroautophagy promotes cellular homeostasis by delivering cytoplasmic constituents to lysosomes for degradation [Mizushima,
MeSH term(s)	Animals ; Fucosidosis/genetics ; Fucosidosis/metabolism ; Lysosomes/metabolism ; Macroautophagy/physiology ; Mice ; Polysaccharides/metabolism ; alpha-L-Fucosidase/genetics ; alpha-L-Fucosidase/metabolism
Chemical Substances	Polysaccharides ; alpha-L-Fucosidase (EC 3.2.1.51)
Language	English
Publishing date	2022-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2111506119
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Article ; Online: Single-Cell and Spatial Transcriptomic Analysis of Human Skin Delineates Intercellular Communication and Pathogenic Cells.

The Journal of investigative dermatology

2023 Volume 143, Issue 11, Page(s) 2177–2192.e13

Abstract: Epidermal homeostasis is governed by a balance between keratinocyte proliferation and differentiation with contributions from cell-cell interactions, but conserved or divergent mechanisms governing this equilibrium across species and how an imbalance ... ...

Abstract	Epidermal homeostasis is governed by a balance between keratinocyte proliferation and differentiation with contributions from cell-cell interactions, but conserved or divergent mechanisms governing this equilibrium across species and how an imbalance contributes to skin disease are largely undefined. To address these questions, human skin single-cell RNA sequencing and spatial transcriptomics data were integrated and compared with mouse skin data. Human skin cell-type annotation was improved using matched spatial transcriptomics data, highlighting the importance of spatial context in cell-type identity, and spatial transcriptomics refined cellular communication inference. In cross-species analyses, we identified a human spinous keratinocyte subpopulation that exhibited proliferative capacity and a heavy metal processing signature, which was absent in mouse and may account for species differences in epidermal thickness. This human subpopulation was expanded in psoriasis and zinc-deficiency dermatitis, attesting to disease relevance and suggesting a paradigm of subpopulation dysfunction as a hallmark of the disease. To assess additional potential subpopulation drivers of skin diseases, we performed cell-of-origin enrichment analysis within genodermatoses, nominating pathogenic cell subpopulations and their communication pathways, which highlighted multiple potential therapeutic targets. This integrated dataset is encompassed in a publicly available web resource to aid mechanistic and translational studies of normal and diseased skin.
MeSH term(s)	Humans ; Animals ; Mice ; Transcriptome ; Skin ; Keratinocytes/metabolism ; Epidermis/pathology ; Skin Diseases/pathology ; Cell Communication
Language	English
Publishing date	2023-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2023.02.040
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Article ; Online: CD97 is associated with mitogenic pathway activation, metabolic reprogramming, and immune microenvironment changes in glioblastoma

Michael M. Safaee / Elaina J. Wang / Saket Jain / Jia-Shu Chen / Sabraj Gill / Allison C. Zheng / Joseph H. Garcia / Angad S. Beniwal / Y. Tran / Alan T. Nguyen / Melissa Trieu / Kevin Leung / Jim Wells / James M. Maclean / Keith Wycoff / Manish K. Aghi

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 13

Abstract: Abstract Glioblastoma (GBM) is the most common primary brain tumor with a median survival under two years. Using in silico and in vitro techniques, we demonstrate heterogeneous expression of CD97, a leukocyte adhesion marker, in human GBM. Beyond its ... ...

Abstract	Abstract Glioblastoma (GBM) is the most common primary brain tumor with a median survival under two years. Using in silico and in vitro techniques, we demonstrate heterogeneous expression of CD97, a leukocyte adhesion marker, in human GBM. Beyond its previous demonstrated role in tumor invasion, we show that CD97 is also associated with upregulation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/Erk) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways in GBM. While CD97 knockout decreased Akt activation, CD97 targeting did not alter MAPK/Erk activation, did not slow GBM cell proliferation in culture, and increased levels of glycolytic and oxidative phosphorylation metabolites. Treatment with a soluble CD97 inhibitor did not alter activation of the MAPK/Erk and PI3K/Akt pathways. Tumors with high CD97 expression were associated with immune microenvironment changes including increased naïve macrophages, regulatory T cells, and resting natural killer (NK) cells. These data suggest that, while CD97 expression is associated with conflicting effects on tumor cell proliferative and metabolic pathways that overall do not affect tumor cell proliferation, CD97 exerts pro-tumoral effects on the tumor immune microenvironment, which along with the pro-invasive effects of CD97 we previously demonstrated, provides impetus to continue exploring CD97 as a therapeutic target in GBM.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CD97 is associated with mitogenic pathway activation, metabolic reprogramming, and immune microenvironment changes in glioblastoma.

Safaee, Michael M / Wang, Elaina J / Jain, Saket / Chen, Jia-Shu / Gill, Sabraj / Zheng, Allison C / Garcia, Joseph H / Beniwal, Angad S / Tran, Y / Nguyen, Alan T / Trieu, Melissa / Leung, Kevin / Wells, Jim / Maclean, James M / Wycoff, Keith / Aghi, Manish K

Scientific reports

2022 Volume 12, Issue 1, Page(s) 1464

Abstract: Glioblastoma (GBM) is the most common primary brain tumor with a median survival under two years. Using in silico and in vitro techniques, we demonstrate heterogeneous expression of CD97, a leukocyte adhesion marker, in human GBM. Beyond its previous ... ...

Abstract	Glioblastoma (GBM) is the most common primary brain tumor with a median survival under two years. Using in silico and in vitro techniques, we demonstrate heterogeneous expression of CD97, a leukocyte adhesion marker, in human GBM. Beyond its previous demonstrated role in tumor invasion, we show that CD97 is also associated with upregulation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/Erk) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways in GBM. While CD97 knockout decreased Akt activation, CD97 targeting did not alter MAPK/Erk activation, did not slow GBM cell proliferation in culture, and increased levels of glycolytic and oxidative phosphorylation metabolites. Treatment with a soluble CD97 inhibitor did not alter activation of the MAPK/Erk and PI3K/Akt pathways. Tumors with high CD97 expression were associated with immune microenvironment changes including increased naïve macrophages, regulatory T cells, and resting natural killer (NK) cells. These data suggest that, while CD97 expression is associated with conflicting effects on tumor cell proliferative and metabolic pathways that overall do not affect tumor cell proliferation, CD97 exerts pro-tumoral effects on the tumor immune microenvironment, which along with the pro-invasive effects of CD97 we previously demonstrated, provides impetus to continue exploring CD97 as a therapeutic target in GBM.
MeSH term(s)	Activation, Metabolic/immunology ; Antigens, CD/genetics ; Antigens, CD/metabolism ; Brain Neoplasms/genetics ; Brain Neoplasms/immunology ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Gene Expression Regulation, Neoplastic/immunology ; Gene Knockdown Techniques ; Gene Knockout Techniques ; Glioblastoma/genetics ; Glioblastoma/immunology ; Glioblastoma/pathology ; Humans ; MAP Kinase Signaling System/drug effects ; MAP Kinase Signaling System/immunology ; Metabolomics ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, G-Protein-Coupled/antagonists & inhibitors ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/genetics ; Tumor Microenvironment/immunology
Chemical Substances	ADGRE5 protein, human ; Antigens, CD ; Receptors, G-Protein-Coupled ; AKT1 protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2022-01-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-05259-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Unveiling the autoreactome: Proteome-wide immunological fingerprints reveal the promise of plasma cell depleting therapy.

Bodansky, Aaron / Yu, David Jl / Rallistan, Alysa / Kalaycioglu, Muge / Boonyaratanakornkit, Jim / Green, Damian J / Gauthier, Jordan / Turtle, Cameron J / Zorn, Kelsey / O'Donovan, Brian / Mandel-Brehm, Caleigh / Asaki, James / Kortbawi, Hannah / Kung, Andrew F / Rackaityte, Elze / Wang, Chung-Yu / Saxena, Aditi / de Dios, Kimberly / Masi, Gianvito /

Nowak, Richard J / O'Connor, Kevin C / Li, Hao / Diaz, Valentina E / Casaletto, Kaitlin B / Gontrum, Eva Q / Chan, Brandon / Kramer, Joel H / Wilson, Michael R / Utz, Paul J / Hill, Joshua A / Jackson, Shaun W / Anderson, Mark S / DeRisi, Joseph L

medRxiv : the preprint server for health sciences

2023

Abstract: ... B-Cell Maturation Antigen (BCMA) profoundly alter an individual's autoreactome, while anti-CD19 and CD-20 therapies have ...

Abstract	The prevalence and burden of autoimmune and autoantibody mediated disease is increasing worldwide, yet most disease etiologies remain unclear. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the effects of these treatments longitudinally are lacking. Here, we leverage advances in programmable-phage immunoprecipitation (PhIP-Seq) methodology to explore the modulation, or lack thereof, of proteome-wide autoantibody profiles in both health and disease. We demonstrate that each individual, regardless of disease state, possesses a distinct set of autoreactivities constituting a unique immunological fingerprint, or "autoreactome", that is remarkably stable over years. In addition to uncovering important new biology, the autoreactome can be used to better evaluate the relative effectiveness of various therapies in altering autoantibody repertoires. We find that therapies targeting B-Cell Maturation Antigen (BCMA) profoundly alter an individual's autoreactome, while anti-CD19 and CD-20 therapies have minimal effects, strongly suggesting a rationale for BCMA or other plasma cell targeted therapies in autoantibody mediated diseases.
Language	English
Publishing date	2023-12-20
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.19.23300188
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Article ; Online: Staphylococcus aureus peptidoglycan (PGN) induces pathogenic autoantibody production via autoreactive B cell receptor clonal selection, implications in systemic lupus erythematosus.

Ning, Wangbin / Cheng, Da / Howe, Philip H / Bian, Chuanxiu / Kamen, Diane L / Luo, Zhenwu / Fu, Xiaoyu / Ogunrinde, Elizabeth / Yang, Liuqing / Wang, Xu / Li, Quan-Zhen / Oates, Jim / Zhang, Weiru / White, David / Wan, Zhuang / Gilkeson, Gary S / Jiang, Wei

Journal of autoimmunity

2022 Volume 131, Page(s) 102860

Abstract: ... were analyzed. Further, the association between plasma S. aureus translocation and systemic ... whereas S. aureus PGN induced pathogenic anti-dsDNA autoantibodies (e.g., prolonged IgG production, low IgM ... autoantibody-mediated kidney damage) in C57BL/6 and/or MRL/lpr mice. However, serum total IgG did not differ. S ...

Abstract	Objectives: There is an intricate interplay between the microbiome and the immune response impacting development of normal immunity and autoimmunity. However, we do not fully understand how the microbiome affects production of natural-like and pathogenic autoantibodies. Peptidoglycan (PGN) is a component of the bacterial cell wall which is highly antigenic. PGNs from different bacteria can differ in their immune regulatory activities. Methods: C57BL/6 and MRL/lpr mice were intraperitoneally injected with saline or PGN from Staphylococcus aureus or Bacillus subtilis. Spleen anti-double-stranded DNA (dsDNA) IgG + B cells were sorted for B-cell receptor sequencing. Serum autoantibody levels and kidney damage were analyzed. Further, the association between plasma S. aureus translocation and systemic lupus erythematosus (SLE) pathogenesis was assessed in women. Results: Administration of B. subtilis PGN induced natural-like anti-dsDNA autoantibodies (e.g., IgM, short lived IgG response, and no tissue damage), whereas S. aureus PGN induced pathogenic anti-dsDNA autoantibodies (e.g., prolonged IgG production, low IgM, autoantibody-mediated kidney damage) in C57BL/6 and/or MRL/lpr mice. However, serum total IgG did not differ. S. aureus PGN induced antibodies with reduced clonality and greater hypermutation of IGHV3-74 in splenic anti-dsDNA IgG + B cells from C57BL/6 mice. Further, S. aureus PGN promoted IgG class switch recombination via toll-like receptor 2. Plasma S. aureus DNA levels were increased in women with SLE versus control women and correlated with levels of lupus-related autoantibodies and renal involvement. Conclusions: S. aureus PGN induces pathogenic autoantibody production, whereas B. subtilis PGN drives production of natural nonpathogenic autoantibodies.
MeSH term(s)	Animals ; Antibodies, Antinuclear ; Autoantibodies ; Cell Wall/pathology ; DNA ; Female ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Lupus Erythematosus, Systemic ; Mice ; Mice, Inbred C57BL ; Mice, Inbred MRL lpr ; Peptidoglycan ; Receptors, Antigen, B-Cell ; Staphylococcus aureus/genetics
Chemical Substances	Antibodies, Antinuclear ; Autoantibodies ; Immunoglobulin G ; Immunoglobulin M ; Peptidoglycan ; Receptors, Antigen, B-Cell ; anti-dsDNA autoantibody ; DNA (9007-49-2)
Language	English
Publishing date	2022-07-08
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	639452-8
ISSN	1095-9157 ; 0896-8411
ISSN (online)	1095-9157
ISSN	0896-8411
DOI	10.1016/j.jaut.2022.102860
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Article ; Online: Endovascular thrombectomy and intravenous alteplase in patients with acute ischemic stroke due to large vessel occlusion: A clinical practice guideline.

Ye, Zhikang / Busse, Jason W / Hill, Michael D / Lindsay, M Patrice / Guyatt, Gordon H / Prasad, Kameshwar / Agarwal, Arnav / Beattie, Cheryl / Beattie, Jim / Dodd, Cynthia / Heran, Manraj K S / Narayan, Sunil / Chartúir, Norita Ní / O'Donnell, Martin / Resmini, Ilaria / Sacco, Simona / Sylaja, P N / Volders, David / Wang, Xin /

Xie, Feng / Zachrison, Kori S / Zhang, Lingli / Zhong, Hongliang / An, Zhuoling / Smith, Eric E

Journal of evidence-based medicine

2022 Volume 15, Issue 3, Page(s) 263–271

Abstract: Aim: Whether or not use of intravenous alteplase in combination with endovascular thrombectomy (EVT) improves outcomes versus EVT alone, for acute stroke patients with large vessel occlusion presenting directly to a comprehensive stroke center, is ... ...

Abstract	Aim: Whether or not use of intravenous alteplase in combination with endovascular thrombectomy (EVT) improves outcomes versus EVT alone, for acute stroke patients with large vessel occlusion presenting directly to a comprehensive stroke center, is uncertain. Methods: Six randomized trials exploring this issue were published, and we synthesized this evidence to inform a rapid guideline based on the Guidelines International Network principles and guided by the GRADE approach. Results: We enlisted an international panel that included 4 patient partners and 1 caregiver, individuals from 6 countries. The panel considered low certainty evidence that EVT alone, relative to EVT with intravenous alteplase, possibly results in a small decrease in the proportion of patients that achieve functional independence and possibly a small increase in mortality. Both effect estimates were downgraded twice due to very serious imprecision. The panel also considered moderate certainty evidence that EVT alone probably decreases symptomatic intracranial hemorrhage, versus EVT with alteplase, and combination therapy was more costly than EVT alone. As a result of the low certainty for improved recovery without impairment and mortality for combination therapy versus EVT alone, and moderate certainty for increased harm with combination therapy, the panel made a weak recommendation in favor of EVT alone for stroke patients eligible for both treatments, and initially presenting directly to a comprehensive stroke center that provides both treatments. Conclusions: Consistent with this weak recommendation, optimal patient management will likely often include co-treatment with intravenous alteplase, depending on local circumstances and patient presentation.
MeSH term(s)	Brain Ischemia/drug therapy ; Brain Ischemia/therapy ; Endovascular Procedures/methods ; Fibrinolytic Agents/therapeutic use ; Humans ; Ischemic Stroke ; Stroke/therapy ; Thrombectomy/methods ; Thrombolytic Therapy/methods ; Tissue Plasminogen Activator/therapeutic use ; Treatment Outcome
Chemical Substances	Fibrinolytic Agents ; Tissue Plasminogen Activator (EC 3.4.21.68)
Language	English
Publishing date	2022-09-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2474496-7
ISSN	1756-5391 ; 1756-5383
ISSN (online)	1756-5391
ISSN	1756-5383
DOI	10.1111/jebm.12493
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