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Article ; Online: Rugby's implementation lessons: the importance of a 'compliance wedge' to support successful implementation for injury prevention.

Raftery, Martin / Falvey, Éanna Cian

2021 Volume 56, Issue 1, Page(s) 1–2

MeSH term(s)	Brain Concussion/prevention & control ; Football/injuries ; Humans ; Rugby
Language	English
Publishing date	2021-02-03
Publishing country	England
Document type	Editorial
ZDB-ID	600592-5
ISSN	1473-0480 ; 0306-3674
ISSN (online)	1473-0480
ISSN	0306-3674
DOI	10.1136/bjsports-2020-103454
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Article ; Online: Response to: World Rugby's erroneous and misleading representation of Australian sports' injury statistics.

Raftery, Martin

British journal of sports medicine

2016 Volume 51, Issue 15, Page(s) 1174

MeSH term(s)	Athletic Injuries ; Australia ; Brain Concussion ; Continental Population Groups ; Football ; Humans ; Sports
Language	English
Publishing date	2016-09-15
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	600592-5
ISSN	1473-0480 ; 0306-3674
ISSN (online)	1473-0480
ISSN	0306-3674
DOI	10.1136/bjsports-2016-096902
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Article: Next-Generation CEA-CAR-NK-92 Cells against Solid Tumors: Overcoming Tumor Microenvironment Challenges in Colorectal Cancer.

Franzén, Alexander Sebastian / Boulifa, Abdelhadi / Radecke, Clarissa / Stintzing, Sebastian / Raftery, Martin J / Pecher, Gabriele

Cancers

2024 Volume 16, Issue 2

Abstract: Colorectal carcinoma (CRC) presents a formidable medical challenge, demanding innovative therapeutic strategies. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy has emerged as a promising alternative to CAR T-cell therapy for cancer. A ... ...

Abstract	Colorectal carcinoma (CRC) presents a formidable medical challenge, demanding innovative therapeutic strategies. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy has emerged as a promising alternative to CAR T-cell therapy for cancer. A suitable tumor antigen target on CRC is carcinoembryonic antigen (CEA), given its widespread expression and role in tumorigenesis and metastasis. CEA is known to be prolifically shed from tumor cells in a soluble form, thus hindering CAR recognition of tumors and migration through the TME. We have developed a next-generation CAR construct exclusively targeting cell-associated CEA, incorporating a PD1-checkpoint inhibitor and a CCR4 chemokine receptor to enhance homing and infiltration of the CAR-NK-92 cell line through the TME, and which does not induce fratricidal killing of CAR-NK-92-cells. To evaluate this therapeutic approach, we harnessed intricate 3D multicellular tumor spheroid models (MCTS), which emulate key elements of the TME. Our results demonstrate the effective cytotoxicity of CEA-CAR-NK-92 cells against CRC in colorectal cell lines and MCTS models. Importantly, minimal off-target activity against non-cancerous cell lines underscores the precision of this therapy. Furthermore, the integration of the CCR4 migration receptor augments homing by recognizing target ligands, CCL17 and CCL22. Notably, our CAR design results in no significant trogocytosis-induced fratricide. In summary, the proposed CEA-targeting CAR-NK cell therapy could offer a promising solution for CRC treatment, combining precision and efficacy in a tailored approach.
Language	English
Publishing date	2024-01-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16020388
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Article: Natural Variation in Age-Related Dopamine Neuron Degeneration is Glutathione-Dependent and Linked to Life Span.

Coleman, Colin R / Pallos, Judit / Arreola-Bustos, Alicia / Wang, Lu / Raftery, Daniel / Promislow, Daniel E L / Martin, Ian

bioRxiv : the preprint server for biology

2024

Abstract: Aging is the biggest risk factor for Parkinson's disease (PD), suggesting that age-related changes in the brain promote dopamine neuron vulnerability. It is unclear, however, whether aging alone is sufficient to cause significant dopamine neuron loss and ...

Abstract	Aging is the biggest risk factor for Parkinson's disease (PD), suggesting that age-related changes in the brain promote dopamine neuron vulnerability. It is unclear, however, whether aging alone is sufficient to cause significant dopamine neuron loss and if so, how this intersects with PD-related neurodegeneration. Here, through examining a large collection of naturally varying
Language	English
Publishing date	2024-02-14
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.12.580013
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Article: Implications for Immunotherapy of Breast Cancer by Understanding the Microenvironment of a Solid Tumor.

Franzén, Alexander S / Raftery, Martin J / Pecher, Gabriele

Cancers

2022 Volume 14, Issue 13

Abstract: Breast cancer is poorly immunogenic due to immunosuppressive mechanisms produced in part by the tumor microenvironment (TME). The TME is a peritumoral area containing significant quantities of (1) cancer-associated fibroblasts (CAF), (2) tumor- ... ...

Abstract	Breast cancer is poorly immunogenic due to immunosuppressive mechanisms produced in part by the tumor microenvironment (TME). The TME is a peritumoral area containing significant quantities of (1) cancer-associated fibroblasts (CAF), (2) tumor-infiltrating lymphocytes (TIL) and (3) tumor-associated macrophages (TAM). This combination protects the tumor from effective immune responses. How these protective cell types are generated and how the changes in the developing tumor relate to these subsets is only partially understood. Immunotherapies targeting solid tumors have proven ineffective largely due to this protective TME barrier. Therefore, a better understanding of the interplay between the tumor, the tumor microenvironment and immune cells would both advance immunotherapeutic research and lead to more effective immunotherapies. This review will summarize the current understanding of the microenvironment of breast cancer giving implications for future immunotherapeutic strategies.
Language	English
Publishing date	2022-06-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14133178
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Article ; Online: Epstein-Barr virus, interleukin-10 and multiple sclerosis: A ménage à trois.

Schönrich, Günther / Abdelaziz, Mohammed O / Raftery, Martin J

Frontiers in immunology

2022 Volume 13, Page(s) 1028972

Abstract: Multiple Sclerosis (MS) is an autoimmune disease that is characterized by inflammation and demyelination of nerve cells. There is strong evidence that Epstein-Barr virus (EBV), a human herpesvirus infecting B cells, greatly increases the risk of ... ...

Abstract	Multiple Sclerosis (MS) is an autoimmune disease that is characterized by inflammation and demyelination of nerve cells. There is strong evidence that Epstein-Barr virus (EBV), a human herpesvirus infecting B cells, greatly increases the risk of subsequent MS. Intriguingly, EBV not only induces human interleukin-10 but also encodes a homologue of this molecule, which is a key anti-inflammatory cytokine of the immune system. Although EBV-encoded IL-10 (ebvIL-10) has a high amino acid identity with its cellular counterpart (cIL-10), it shows more restricted and partially weaker functionality. We propose that both EBV-induced cIL-10 and ebvIL-10 act in a temporally and functionally coordinated manner helping the pathogen to establish latency in B cells and, at the same time, to balance the function of antiviral T cells. As a result, the EBV load persisting in the immune system is kept at a constant but individually different level (set point). During this immunological tug of war between virus and host, however, MS can be induced as collateral damage if the set point is too high. Here, we discuss a possible role of ebvIL-10 and EBV-induced cIL-10 in EBV-driven pathogenesis of MS.
MeSH term(s)	Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections ; Interleukin-10/metabolism ; Multiple Sclerosis/etiology ; Fenofibrate ; Antiviral Agents/metabolism ; Amino Acids/metabolism
Chemical Substances	Interleukin-10 (130068-27-8) ; Fenofibrate (U202363UOS) ; Antiviral Agents ; Amino Acids
Language	English
Publishing date	2022-10-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1028972
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Article ; Online: Concussion and chronic traumatic encephalopathy: International Rugby Board's response.

Raftery, Martin

British journal of sports medicine

2014 Volume 48, Issue 2, Page(s) 79–80

MeSH term(s)	Brain Concussion/prevention & control ; Brain Injury, Chronic/prevention & control ; Football/injuries ; Humans ; Recovery of Function ; Risk Factors
Language	English
Publishing date	2014-01
Publishing country	England
Document type	Editorial
ZDB-ID	600592-5
ISSN	1473-0480 ; 0306-3674
ISSN (online)	1473-0480
ISSN	0306-3674
DOI	10.1136/bjsports-2013-093051
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Article ; Online: Role of beta-(1→3)(1→6)-D-glucan derived from yeast on natural killer (NK) cells and breast cancer cell lines in 2D and 3D cultures.

Boulifa, Abdelhadi / Raftery, Martin J / Franzén, Alexander Sebastian / Radecke, Clarissa / Stintzing, Sebastian / Blohmer, Jens-Uwe / Pecher, Gabriele

BMC cancer

2024 Volume 24, Issue 1, Page(s) 339

Abstract: Background: Beta-(1,3)(1,6)-D-glucan is a complex polysaccharide, which is found in the cell wall of various fungi, yeasts, bacteria, algae, barley, and oats and has immunomodulatory, anticancer and antiviral effects. In the present study, we ... ...

Abstract	Background: Beta-(1,3)(1,6)-D-glucan is a complex polysaccharide, which is found in the cell wall of various fungi, yeasts, bacteria, algae, barley, and oats and has immunomodulatory, anticancer and antiviral effects. In the present study, we investigated the effect of beta-(1,3)(1,6)-D-glucan derived from yeast on the proliferation of primary NK cells and breast cancer cell lines in 2D and 3D models, and on the cytotoxicity of primary NK cells against breast cancer cell lines in 2D and 3D models. Methods: In this study, we investigated the effects of different concentrations of yeast-derived beta-(1→3)(1→6)-D-glucan on the proliferation and cytotoxicity of human NK cells and breast cancer cell lines in 2D and 3D models using the XTT cell proliferation assay and the CellTiter-Glo® 2.0 assay to determine the cytotoxicity of human NK cells on breast cancer cell lines in 2D and 3D models. Results: We found that the co-incubation of NK cells with beta-glucan in the absence of IL2 at 48 h significantly increased the proliferation of NK cells, whereas the co-incubation of NK cells with beta-glucan in the presence of IL2 (70 U/ml) increased the proliferation of NK cells but not significantly. Moreover, beta-glucan significantly inhibited the proliferation of breast cancer cell lines in 2D model and induced a weak, non-significant growth inhibitory effect on breast cancer multicellular tumor spheroids (3D). In addition, the cytotoxicity of NK cells against breast cancer cell lines was examined in 2D and 3D models, and beta-glucan significantly increased the cytotoxicity of NK cells against MCF-7 (in 2D). Conclusions: Yeast derived beta-(1,3)(1,6)-D-glucan could contribute to the treatment of cancer by enhancing NK cell immune response as well as contributing to inhibition of breast cancer cell growth.
MeSH term(s)	Humans ; Female ; MCF-7 Cells ; Glucans/pharmacology ; Breast Neoplasms/pathology ; Saccharomyces cerevisiae ; Interleukin-2 ; Killer Cells, Natural ; beta-Glucans/pharmacology
Chemical Substances	Glucans ; Interleukin-2 ; beta-Glucans
Language	English
Publishing date	2024-03-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-024-11979-3
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Article ; Online: Symptom presentation and evolution in the first 48 hours after injury are associated with return to play after concussion in elite Rugby Union.

Tucker, Ross / Cross, Matt / Stokes, Keith / Starling, Lindsay / Hyman, Rosy / Kemp, Simon / West, Stephen / Raftery, Martin / Falvey, Eanna / Brown, James

Journal of sport and health science

2024

Abstract: Background: Return to play (RTP) in elite rugby is managed using a 6-stage graduated RTP protocol, which can result in clearance to play within 1 week of injury. We aimed to explore how symptom, cognitive, and balance presentation and evolution during ... ...

Abstract	Background: Return to play (RTP) in elite rugby is managed using a 6-stage graduated RTP protocol, which can result in clearance to play within 1 week of injury. We aimed to explore how symptom, cognitive, and balance presentation and evolution during concussion screens 2 h (head injury assessment (HIA) 2) and 48 h (HIA3) after injury were associated with time to RTP) to identify whether a more conservative graduated RTP may be appropriate. Methods: A retrospective cohort study was conducted in 380 concussed rugby players from elite men's rugby over 3 consecutive seasons. Players were classified as shorter or longer returns, depending on whether RTP occurred within 7 days (allowing them to be considered to play the match 1 week after injury) or longer than 8 days, respectively. Symptom, cognitive, and balance performance during screens was assessed relative to baseline (normal or abnormal) and to the preceding screen (improving or worsening). Associations between sub-test abnormalities and RTP time were explored using odds ratios (OR, longer vs. shorter). Median day absence was compared between players with abnormal or worsening results and those whose results were normal or improving. Results: Abnormal symptom results during screens 2 h and 48 h after concussion were associated with longer return time (HIA2: OR = 2.21, 95% confidence interval (95%CI): 1.39-3.50; HIA3: OR = 3.30, 95%CI: 1.89-5.75). Worsening symptom number or severity from the time of injury to 2 h and 48 h post-injury was associated with longer return (HIA2: OR = 2.49, 95%CI: 1.36-4.58; HIA3: OR = 3.34, 95%CI: 1.10-10.15. Median days absence was greater in players with abnormal symptom results at both HIA2 and HIA3. Cognitive and balance performance were not associated with longer return and did not affect median days absence. Conclusion: Symptom presentation and evolution within 48 h of concussion were associated with longer RTP times. This may guide a more conservative approach to RTP, while still adhering to individualized concussion management principles.
Language	English
Publishing date	2024-01-15
Publishing country	China
Document type	Journal Article
ZDB-ID	2673028-5
ISSN	2213-2961 ; 2095-2546
ISSN (online)	2213-2961
ISSN	2095-2546
DOI	10.1016/j.jshs.2024.01.005
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Article: Head injury assessment in rugby union: clinical judgement guidelines.

Falvey, Éanna / Tucker, Ross / Fuller, Gordan / Raftery, Martin

BMJ open sport & exercise medicine

2021 Volume 7, Issue 2, Page(s) e000986

Abstract: Background/aim: Clinical judgement is a recognised component of a complete off-field concussion assessment. This study identifies guidance criteria for team medical staff when using clinical judgement in their decision-making process during the World ... ...

Abstract	Background/aim: Clinical judgement is a recognised component of a complete off-field concussion assessment. This study identifies guidance criteria for team medical staff when using clinical judgement in their decision-making process during the World Rugby off-field concussion-assessment screen (HIA1). Methods: Retrospective study of examining doctor clinical judgement in 1149 HIA1 assessments after a meaningful head impact event completed on rugby union players participating in elite-level international and national competitions between September 2015 and June 2018. We assessed (1) an abnormal subtest result as worse performance compared with preseason baseline values; (2) the proportion of cases where clinicians overruled abnormal HIA1 assessment subtest results and (3) made recommendations on how clinical judgement decisions may be made more safely based on the accuracy of clinical judgement decisions assessed against the final concussion diagnosis. Results: One or more subtests were abnormal compared with baseline values in 857 of 1149 HIA1 assessments. Clinical judgement was used to return players to the game despite abnormal subtest results on 424 out of 857 occasions (49%). In a significant majority of cases 356/424 (84%), clinical judgement decisions were correct, with players later cleared of a concussion. An application of guided clinical judgement potentially decreased false negative assessments by 33% (21/63). Conclusions: Clinical judgement should be applied in the diagnosis of concussion but done so cautiously. We propose doctors should only use clinical judgement to overrule either one of; or a combination of (1) an abnormal tandem gait and (2) one abnormal cognitive test.
Language	English
Publishing date	2021-04-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2817580-3
ISSN	2055-7647
ISSN	2055-7647
DOI	10.1136/bmjsem-2020-000986
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