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Article ; Online: Neutrophil serine proteases in vitro: How much and why?

Patterson, Eric K / Fraser, Douglas D / Cepinskas, Gediminas

2022 Volume 112, Issue 4, Page(s) 585–586

MeSH term(s)	Cathepsin G ; Neutrophils ; Serine Proteases
Chemical Substances	Serine Proteases (EC 3.4.-) ; Cathepsin G (EC 3.4.21.20)
Language	English
Publishing date	2022-09-08
Publishing country	United States
Document type	Letter
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1002/JLB.3LT0722-360R
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Article ; Online: Anticytokine Therapies in Severe Coronavirus Disease 2019 Should Be Informed by Detailed Inflammatory Profiling and Specific Therapeutic Targets.

Slessarev, Marat / Fraser, Douglas D

Critical care explorations

2020 Volume 2, Issue 10, Page(s) e0246

Keywords	covid19
Language	English
Publishing date	2020-10-15
Publishing country	United States
Document type	Journal Article
ISSN	2639-8028
ISSN (online)	2639-8028
DOI	10.1097/CCE.0000000000000246
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Article ; Online: The plasma proteome differentiates the multisystem inflammatory syndrome in children (MIS-C) from children with SARS-CoV-2 negative sepsis.

Patel, Maitray A / Fraser, Douglas D / Daley, Mark / Cepinskas, Gediminas / Veraldi, Noemi / Grazioli, Serge

Molecular medicine (Cambridge, Mass.)

2024 Volume 30, Issue 1, Page(s) 51

Abstract: Background: The Multi-System Inflammatory Syndrome in Children (MIS-C) can develop several weeks after SARS-CoV-2 infection and requires a distinct treatment protocol. Distinguishing MIS-C from SARS-CoV-2 negative sepsis (SCNS) patients is important to ... ...

Abstract	Background: The Multi-System Inflammatory Syndrome in Children (MIS-C) can develop several weeks after SARS-CoV-2 infection and requires a distinct treatment protocol. Distinguishing MIS-C from SARS-CoV-2 negative sepsis (SCNS) patients is important to quickly institute the correct therapies. We performed targeted proteomics and machine learning analysis to identify novel plasma proteins of MIS-C for early disease recognition. Methods: A case-control study comparing the expression of 2,870 unique blood proteins in MIS-C versus SCNS patients, measured using proximity extension assays. The 2,870 proteins were reduced in number with either feature selection alone or with a prior COMBAT-Seq batch effect adjustment. The leading proteins were correlated with demographic and clinical variables. Organ system and cell type expression patterns were analyzed with Natural Language Processing (NLP). Results: The cohorts were well-balanced for age and sex. Of the 2,870 unique blood proteins, 58 proteins were identified with feature selection (FDR-adjusted P < 0.005, P < 0.0001; accuracy = 0.96, AUC = 1.00, F1 = 0.95), and 15 proteins were identified with a COMBAT-Seq batch effect adjusted feature selection (FDR-adjusted P < 0.05, P < 0.0001; accuracy = 0.92, AUC = 1.00, F1 = 0.89). All of the latter 15 proteins were present in the former 58-protein model. Several proteins were correlated with illness severity scores, length of stay, and interventions (LTA4H, PTN, PPBP, and EGF; P < 0.001). NLP analysis highlighted the multi-system nature of MIS-C, with the 58-protein set expressed in all organ systems; the highest levels of expression were found in the digestive system. The cell types most involved included leukocytes not yet determined, lymphocytes, macrophages, and platelets. Conclusions: The plasma proteome of MIS-C patients was distinct from that of SCNS. The key proteins demonstrated expression in all organ systems and most cell types. The unique proteomic signature identified in MIS-C patients could aid future diagnostic and therapeutic advancements, as well as predict hospital length of stays, interventions, and mortality risks.
MeSH term(s)	Child ; Humans ; Proteome ; SARS-CoV-2 ; COVID-19/complications ; Case-Control Studies ; Proteomics ; Systemic Inflammatory Response Syndrome ; Sepsis ; Blood Proteins
Chemical Substances	Proteome ; Blood Proteins
Language	English
Publishing date	2024-04-17
Publishing country	England
Document type	Journal Article
ZDB-ID	1283676-x
ISSN	1528-3658 ; 1076-1551
ISSN (online)	1528-3658
ISSN	1076-1551
DOI	10.1186/s10020-024-00806-x
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Article ; Online: Differences in career paths of alumni of the Cornell Leadership Program from North American universities compared with those alumni from universities in other countries.

Fraser, David R / Parker, John S L / McGregor, Douglas D

Journal of the American Veterinary Medical Association

2023 Volume 261, Issue 5, Page(s) 718–722

Abstract: Objective: To characterize and compare the careers of alumni of the Cornell Leadership Program for Veterinary Students according to the countries where they studied and obtained their veterinary qualification. The Cornell Leadership Program is a 10-week ...

Abstract	Objective: To characterize and compare the careers of alumni of the Cornell Leadership Program for Veterinary Students according to the countries where they studied and obtained their veterinary qualification. The Cornell Leadership Program is a 10-week residential research experience program for veterinary students from around the world who have ambitions for research-related careers. Sample: Data on the career development of all 672 alumni were collected each year over the period of 1990 to 2019. Procedures: The annual career profile of each alumnus was recorded and coded in 1 of 28 different categories. The careers and postveterinary qualifications of alumni from universities in the US and Canada (referred to as North American universities) were compared with those alumni who graduated from universities in other countries. Results: Analysis of this 30-year database revealed that a considerable proportion (45.7% [307/672]) of the total 672 alumni are following the traditional career path of veterinary clinical practice rather than the research-related careers they aspired to as students during the Leadership Program. Furthermore, a higher proportion of the 325 North American alumni (56% [182/325]) were in clinical practice compared with 33.6% (112/333) of the 333 alumni from other countries. Clinical relevance: Many veterinary schools now provide research experience programs to encourage highly talented students who have ambitions for careers in which they can advance knowledge about animal disease and contribute to solving the health problems of animals through hypothesis-based research. Comparison of the careers of the Leadership Program alumni indicates that research experience alone is not sufficient to maintain the career goals of alumni. Follow-up mentoring of alumni of such programs is recommended while they complete their veterinary studies to reinforce their career aspirations and provide advice on how to achieve research-related careers.
MeSH term(s)	Animals ; Humans ; Leadership ; Universities ; Students ; Canada ; Schools, Veterinary ; Career Choice
Language	English
Publishing date	2023-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	390811-2
ISSN	1943-569X ; 0003-1488
ISSN (online)	1943-569X
ISSN	0003-1488
DOI	10.2460/javma.22.10.0461
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Article: Endothelial Glycocalyx Degradation in Critical Illness and Injury.

Patterson, Eric K / Cepinskas, Gediminas / Fraser, Douglas D

Frontiers in medicine

2022 Volume 9, Page(s) 898592

Abstract: The endothelial glycocalyx is a gel-like layer on the luminal side of blood vessels that is composed of glycosaminoglycans and the proteins that tether them to the plasma membrane. Interest in its properties and function has grown, particularly in the ... ...

Abstract	The endothelial glycocalyx is a gel-like layer on the luminal side of blood vessels that is composed of glycosaminoglycans and the proteins that tether them to the plasma membrane. Interest in its properties and function has grown, particularly in the last decade, as its importance to endothelial barrier function has come to light. Endothelial glycocalyx studies have revealed that many critical illnesses result in its degradation or removal, contributing to endothelial dysfunction and barrier break-down. Loss of the endothelial glycocalyx facilitates the direct access of immune cells and deleterious agents (e.g., proteases and reactive oxygen species) to the endothelium, that can then further endothelial cell injury and dysfunction leading to complications such as edema, and thrombosis. Here, we briefly describe the endothelial glycocalyx and the primary components thought to be directly responsible for its degradation. We review recent literature relevant to glycocalyx damage in several critical illnesses (sepsis, COVID-19, trauma and diabetes) that share inflammation as a common denominator with actions by several common agents (hyaluronidases, proteases, reactive oxygen species, etc.). Finally, we briefly cover strategies and therapies that show promise in protecting or helping to rebuild the endothelial glycocalyx such as steroids, protease inhibitors, anticoagulants and resuscitation strategies.
Language	English
Publishing date	2022-07-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2022.898592
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Article: Discussion of development processes in insect-fungus association derived from the shaggy parasol fruiting on the nests of hairy wood ants.

Fraser, Douglas

Ecology and evolution

2019 Volume 9, Issue 20, Page(s) 11619–11630

Abstract: Chlorophyllum ... ...

Abstract	Chlorophyllum rhacodes
Language	English
Publishing date	2019-09-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2635675-2
ISSN	2045-7758
ISSN	2045-7758
DOI	10.1002/ece3.5611
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Article ; Online: Endothelial Glycocalyx Degradation in Critical Illness and Injury

Eric K. Patterson / Gediminas Cepinskas / Douglas D. Fraser

Frontiers in Medicine, Vol

2022 Volume 9

Abstract	The endothelial glycocalyx is a gel-like layer on the luminal side of blood vessels that is composed of glycosaminoglycans and the proteins that tether them to the plasma membrane. Interest in its properties and function has grown, particularly in the last decade, as its importance to endothelial barrier function has come to light. Endothelial glycocalyx studies have revealed that many critical illnesses result in its degradation or removal, contributing to endothelial dysfunction and barrier break-down. Loss of the endothelial glycocalyx facilitates the direct access of immune cells and deleterious agents (e.g., proteases and reactive oxygen species) to the endothelium, that can then further endothelial cell injury and dysfunction leading to complications such as edema, and thrombosis. Here, we briefly describe the endothelial glycocalyx and the primary components thought to be directly responsible for its degradation. We review recent literature relevant to glycocalyx damage in several critical illnesses (sepsis, COVID-19, trauma and diabetes) that share inflammation as a common denominator with actions by several common agents (hyaluronidases, proteases, reactive oxygen species, etc.). Finally, we briefly cover strategies and therapies that show promise in protecting or helping to rebuild the endothelial glycocalyx such as steroids, protease inhibitors, anticoagulants and resuscitation strategies.
Keywords	glycocalyx ; inflammation ; sepsis ; trauma ; endothelium ; Medicine (General) ; R5-920
Subject code	570
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Pediatric sepsis inflammatory blood biomarkers that correlate with clinical variables and severity of illness scores.

Leonard, Sean / Guertin, Hailey / Odoardi, Natalya / Miller, Michael R / Patel, Maitray A / Daley, Mark / Cepinskas, Gediminas / Fraser, Douglas D

Journal of inflammation (London, England)

2024 Volume 21, Issue 1, Page(s) 7

Abstract: Background: Sepsis is a dysregulated systemic inflammatory response triggered by infection, resulting in organ dysfunction. A major challenge in clinical pediatrics is to identify sepsis early and then quickly intervene to reduce morbidity and mortality. ...

Abstract	Background: Sepsis is a dysregulated systemic inflammatory response triggered by infection, resulting in organ dysfunction. A major challenge in clinical pediatrics is to identify sepsis early and then quickly intervene to reduce morbidity and mortality. As blood biomarkers hold promise as early sepsis diagnostic tools, we aimed to measure a large number of blood inflammatory biomarkers from pediatric sepsis patients to determine their predictive ability, as well as their correlations with clinical variables and illness severity scores. Methods: Pediatric patients that met sepsis criteria were enrolled, and clinical data and blood samples were collected. Fifty-eight inflammatory plasma biomarker concentrations were determined using immunoassays. The data were analyzed with both conventional statistics and machine learning. Results: Twenty sepsis patients were enrolled (median age 13 years), with infectious pathogens identified in 75%. Vasopressors were administered to 85% of patients, while 55% received invasive ventilation and 20% were ventilated non-invasively. A total of 24 inflammatory biomarkers were significantly different between sepsis patients and age/sex-matched healthy controls. Nine biomarkers (IL-6, IL-8, MCP-1, M-CSF, IL-1RA, hyaluronan, HSP70, MMP3, and MMP10) yielded AUC parameters > 0.9 (95% CIs: 0.837-1.000; p < 0.001). Boruta feature reduction yielded 6 critical biomarkers with their relative importance: IL-8 (12.2%), MCP-1 (11.6%), HSP70 (11.6%), hyaluronan (11.5%), M-CSF (11.5%), and IL-6 (11.5%); combinations of 2 biomarkers yielded AUC values of 1.00 (95% CI: 1.00-1.00; p < 0.001). Specific biomarkers strongly correlated with illness severity scoring, as well as other clinical variables. IL-3 specifically distinguished bacterial versus viral infection (p < 0.005). Conclusions: Specific inflammatory biomarkers were identified as markers of pediatric sepsis and strongly correlated to both clinical variables and sepsis severity.
Language	English
Publishing date	2024-03-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2164385-4
ISSN	1476-9255
ISSN	1476-9255
DOI	10.1186/s12950-024-00379-w
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Article: Pharmacokinetics of recombinant human annexin A5 (SY-005) in patients with severe COVID-19.

Tschirhart, Brent J / Lu, Xiangru / Mokale Kognou, Aristide Laurel / Martin, Claudio M / Slessarev, Marat / Fraser, Douglas D / Leligdowicz, Aleksandra / Urquhart, Bradley / Feng, Qingping

Frontiers in pharmacology

2024 Volume 14, Page(s) 1299613

Abstract: Objective: ...

Abstract	Objective:
Language	English
Publishing date	2024-01-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1299613
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Article: Pivoting injury prevention efforts during a pandemic: results of an international survey.

Charyk Stewart, Tanya / Unni, Purnima / Hanson, Holly Renee / Gilliland, Jason / Clark, Andrew / Fraser, Douglas D

Injury epidemiology

2023 Volume 10, Issue Suppl 1, Page(s) 59

Abstract: Background: The COVID-19 a pandemic changed the world. Public health directives to socially distance with stay-at-home orders altered injury risk factor exposure, resulting injury patterns and conducting injury prevention (IP). The objective of this ... ...

Abstract	Background: The COVID-19 a pandemic changed the world. Public health directives to socially distance with stay-at-home orders altered injury risk factor exposure, resulting injury patterns and conducting injury prevention (IP). The objective of this study was to determine the impact the COVID-19 pandemic on injury and IP at North American trauma centers (TC). Results: Sixty-two responses were received from pediatric (44%), adult (11%), and combined (31%) TC, from 22 American states, 5 Canadian provinces and Australia. The majority (91%) of programs targeted age groups from birth to 15 years old. Nearly one-third reported IP to be less of an institutional priority with funding redistributed in 15% of centers [median (IQR) - 25% (- 43, 1)], and resultant staffing changes at 38% of centers. A decrease in IP efforts was reported at 64% of TC. Overall, the majority of respondents reviewed injury data, with the top reported increased mechanisms mainly intentional: Firearm-related (75%), assaults (72%), and abuse (71%). Leading increased unintentional injuries were injuries occurring in the home such as falls (70%), followed by ATV (62%), and cycling (57%). Sites pivoted by presenting (74%) or participating (73%) in IP education virtually, social media posts (61%) and the addition of technology (29%). Top barriers were redeployment of partners (45%) and staff (31%), as well as lack of technology (40%) in the target population. Facilitators were technology at TC (74%), support of trauma program (63%), and having IP funding maintained (55%). Conclusions: Nearly two-thirds of TC decreased IP efforts during the pandemic due to staffing and funding reductions. The leading reported increased injuries were intentional, indicating that violence prevention is needed, along with support for mental health. While TC successfully pivoted by using technology, access issues in the target population was a barrier resulting in health inequities.
Language	English
Publishing date	2023-11-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2764253-7
ISSN	2197-1714
ISSN	2197-1714
DOI	10.1186/s40621-023-00472-3
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