Medicine and Health Sciences Commons^™

Circulating Pre-Treatment T-Cell Receptor Repertoire As A Predictive Biomarker In Advanced Or Metastatic Non-Small-Cell Lung Cancer Patients Treated With Pembrolizumab Alone Or In Combination With Chemotherapy, A. Abed, Aaron B. Beasley, Anna L. Reid, N. Law, L. Calapre, M. Millward, Johnny Lo, Elin S. Gray

Research outputs 2022 to 2026

Background: The circulating T-cell receptor (TCR) repertoire is a dynamic representation of overall immune responses in an individual. Materials and methods: We prospectively collected baseline blood from patients treated with first-line pembrolizumab monotherapy or in combination with chemotherapy. TCR repertoire metrics were correlated with clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS) and immune-related adverse events (irAEs). We built a logistic regression classifier by fitting all four TCR- repertoire metrics to the immune checkpoint inhibitor (ICI) CBR data. In the subsequent receiver operating characteristic (ROC) analysis of the resulting logistic regression model probabilities, the best cut-off value was …

The Relationship Between Clinical Phenotype And Kallikrein-Kinin Bioregulation In Different Forms Of Arthritis, Dino B. A. Tan, Chantalia Tedja, Lukas Kuster, Warren D. Raymond, Andreea Harsanyi, Priya V. Chowalloor, Neil L. Misso, Shashi Argawal, Kanti D. Bhoola, Helen I. Keen

Research outputs 2022 to 2026

Objective: Patients with rheumatoid arthritis (RA) have shown increased levels of neutrophils generating kallikrein-kinin peptides in blood which are potent mediators of inflammation. This study investigated the association between the bioregulation of kinin-mediated inflammation with the clinical, quality of life, and imaging characteristics (e.g. ultrasonography) of different arthritides. Methods: Patients with osteoarthritis (OA, n = 29), gout (n = 10) and RA (n = 8) were recruited and screened for clinical symptoms, quality of life, and ultrasonographical assessment of arthritis. Blood neutrophils were assessed for the expression of bradykinin receptors (B1R and B2R), kininogens and kallikreins by immunocytochemistry with visualization …

Recent Developments In Frailty Identification, Management, Risk Factors And Prevention: A Narrative Review Of Leading Journals In Geriatrics And Gerontology, Elsa Dent, Peter Hanlon, Marc Sim, Juulia Jylhävä, Zuyun Liu, Davide L. Vetrano, Erwin Stolz, Mario U. Pérez-Zepeda, Daniel R. Crabtree, Caroline Nicholson, Jenny Job, Rachel C. Ambagtsheer, Paul R. Ward, Sandra M. Shi, Quan Huynh, Emiel O. Hoogendijk

Research outputs 2022 to 2026

Frailty is an age-related clinical condition characterised by an increased susceptibility to stressors and an elevated risk of adverse outcomes such as mortality. In the light of global population ageing, the prevalence of frailty is expected to soar in coming decades. This narrative review provides critical insights into recent developments and emerging practices in frailty research regarding identification, management, risk factors, and prevention. We searched journals in the top two quartiles of geriatrics and gerontology (from Clarivate Journal Citation Reports) for articles published between 01 January 2018 and 20 December 2022. Several recent developments were identified, including new biomarkers and …

Ifi27 Transcription Is An Early Predictor For Covid-19 Outcomes, A Multi-Cohort Observational Study, Maryam Shojaei, Amir Shamshirian, James Monkman, Laura Grice, Minh Tran, Chin Wee Tan, Siok Min Teo, Gustavo Rodrigues Rossi, Timothy R. Mcculloch, Marek Nalos, Maedeh Raei, Alireza Razavi, Roya Ghasemian, Mobina Gheibi, Fatemeh Roozbeh, Peter D. Sly, Kirsten M. Spann, Keng Yih Chew, Yanshan Zhu, Yao Xia, Timothy J. Wells, Alexandra Cristina Senegaglia, Carmen Lúcia Kuniyoshi, Claudio Luciano Franck, Anna Flavia Ribeiro Dos Santos, Lucia De Noronha, Sepideh Motamen, Reza Valadan, Omolbanin Amjadi, Rajan Gogna, Esha Madan, Reza Alizadeh-Navaei, Liliana Lamperti, Felipe Zuñiga, Estefania Nova-Lamperti, Gonzalo Labarca, Ben Knippenberg, Velma Herwanto, Ya Wang, Amy Phu, Tracy Chew, Timothy Kwan, Karan Kim, Sally Teoh, Tiana M. Pelaia, Win Sen Kuan, Yvette Jee, Jon Iredell, Ken O’Byrne, John F. Fraser, Melissa J. Davis, Gabrielle T. Belz, Majid E. Warkiani, Carlos Salomon Gallo, Fernando Souza-Fonseca-Guimaraes, Quan Nguyen, Anthony Mclean, Arutha Kulasinghe, Kirsty R. Short, Benjamin Tang

Research outputs 2022 to 2026

Purpose:

Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness.

Methods:

We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients.

Results:

We show that IFI27 is …

Discovery Of A Missense Mutation (Q222k) Of The Apoe Gene From The Australian Imaging, Biomarker And Lifestyle Study, Blaine R. Roberts, Scott B. Laffoon, Anne M. Roberts, Tenielle Porter, Chris Fowler, Colin L. Masters, Edward A. Dratz, Simon M. Laws

Research outputs 2022 to 2026

After age, polymorphisms of the Apolipoprotein E (APOE) gene are the biggest risk factor for the development of Alzheimer's disease (AD). During our investigation to discovery biomarkers in plasma, using 2D gel electrophoresis, we found an individual with and unusual apoE isoelectric point compared to APOE ϵ2, ϵ3, and ϵ4 carriers. Whole exome sequencing of APOE from the donor confirmed a single nucleotide polymorphism (SNP) in exon 4, translating to a rare Q222K missense mutation. The apoE ϵ4 (Q222K) mutation did not form dimers or complexes observed for apoE ϵ2 ϵ3 proteins.

Plasma Glial Fibrillary Acidic Protein Is Associated With 18f-Smbt-1 Pet: Two Putative Astrocyte Reactivity Biomarkers For Alzheimer's Disease, Pratishtha Chatterjee, Vincent Doré, Steve Pedrini, Natasha Krishnadas, Rohith Thota, Pierrick Bourgeat, Milos D. Ikonomovic, Stephanie R. Rainey-Smith, Samantha C. Burnham, Christopher Fowler, Kevin Taddei, Rachel Mulligan, David Ames, Colin L. Masters, Jürgen Fripp, Christopher C. Rowe, Ralph N. Martins, Victor L. Villemagne, Aibl Research Group

Research outputs 2022 to 2026

Background:

Astrocyte reactivity is an early event along the Alzheimer's disease (AD) continuum. Plasma glial fibrillary acidic protein (GFAP), posited to reflect astrocyte reactivity, is elevated across the AD continuum from preclinical to dementia stages. Monoamine oxidase-B (MAO-B) is also elevated in reactive astrocytes observed using ¹⁸F-SMBT-1 PET in AD.

Objective:

The objective of this study was to evaluate the association between the abovementioned astrocyte reactivity biomarkers.

Methods:

Plasma GFAP and Aβ were measured using the Simoa^® platform in participants who underwent brain ¹⁸F-SMBT-1 and Aβ-PET imaging, comprising 54 healthy control (13 Aβ-PET+ and 41 Aβ-PET-), 11 …

Identification And Validation Of Igg N-Glycosylation Biomarkers Of Esophageal Carcinoma, Huiying Pan, Zhiyuan Wu, Haiping Zhang, Jie Zhang, Yue Liu, Zhiwei Li, Wei Feng, Guiqi Wang, Yong Liu, Deli Zhao, Zhiyi Zhang, Yuqin Liu, Zhe Zhang, Xiangtong Liu, Lixin Tao, Yanxia Luo, Xiaonan Wang, Xinghua Yang, Feng Zhang, Xia Li, Xiuhua Guo

Research outputs 2022 to 2026

Introduction: Altered Immunoglobulin G (IgG) N-glycosylation is associated with aging, inflammation, and diseases status, while its effect on esophageal squamous cell carcinoma (ESCC) remains unknown. As far as we know, this is the first study to explore and validate the association of IgG N-glycosylation and the carcinogenesis progression of ESCC, providing innovative biomarkers for the predictive identification and targeted prevention of ESCC. Methods: In total, 496 individuals of ESCC (n=114), precancerosis (n=187) and controls (n=195) from the discovery population (n=348) and validation population (n=148) were recruited in the study. IgG N-glycosylation profile was analyzed and an ESCC-related glycan score was …

Sixteen-Year Longitudinal Evaluation Of Blood-Based Dna Methylation Biomarkers For Early Prediction Of Alzheimer's Disease, Fernanda Schäfer Hackenhaar, Maria Josefsson, Annelie Nordin Adolfsson, Mattias Landfors, Karolina Kauppi, Tenielle Porter, Lidija Milicic, Simon M. Laws, Magnus Hultdin, Rolf Adolfsson, Sofie Degerman, Sara Pudas, Australian Imaging Biomarkers And Lifestyle Study

Research outputs 2022 to 2026

BACKGROUND: DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, has shown promise for Alzheimer's disease (AD) prediction. OBJECTIVE: Testing long-term predictive ability ( > 15 years) of existing DNAm-based epigenetic age acceleration (EAA) measures and identifying novel early blood-based DNAm AD-prediction biomarkers. METHODS: EAA measures calculated from Illumina EPIC data from blood were tested with linear mixed-effects models (LMMs) in a longitudinal case-control sample (50 late-onset AD cases; 51 matched controls) with prospective data up to 16 years before clinical onset, and post-onset follow-up. Novel DNAm biomarkers were generated with epigenome-wide LMMs, and Sparse Partial Least Squares …

Association Between Immunoglobulin G N-Glycosylation And Lupus Nephritis In Female Patients With Systemic Lupus Erythematosus: A Case-Control Study, Xinxia Lu, Liangao Wang, Meng Wang, Yuejin Li, Qinqin Zhao, Yanjun Shi, Yujing Zhang, Yingjie Wang, Wei Wang, Long Ji, Haifeng Hou, Dong Li

Research outputs 2022 to 2026

Background: Lupus nephritis (LN) is a crucial complication of systemic lupus erythematosus (SLE) and has important clinical implications in guiding treatment. N-glycosylation of immunoglobulin G (IgG) plays a key role in the development of SLE by affecting the balance of anti-inflammatory and proinflammatory responses. This study aimed to evaluate the performance of IgG N-glycosylation for diagnosing LN in a sample of female SLE patients. Methods: This case-control study recruited 188 women with SLE, including 94 patients with LN and 94 age-matched patients without LN. The profiles of plasma IgG N-glycans were detected by hydrophilic interaction chromatography with ultra-performance liquid chromatography …

Detectable Ctdna At The Time Of Treatment Cessation Of Ipilimumab And Nivolumab For Toxicity Predicts Disease Progression In Advanced Melanoma Patients, Lydia Warburton, Anna Reid, Benhur Amanuel, Leslie Calapre, Michael Millward, Elin Gray

Research outputs 2022 to 2026

Background: Immune checkpoint inhibition (ICI) has led to unprecedented outcomes for melanoma patients but is associated with toxicity. ICI resumption after high grade irAEs poses a significant challenge in the clinical management of melanoma patients and there are no biomarkers that can help identify patients that might benefit from resuming treatment. This study aims to determine if circulating tumor DNA (ctDNA) levels at the time of treatment-limiting irAE could guide treatment decisions in this clinical context. Methods: This is a retrospective exploratory biomarker study from 34 patients treated with combination ICI for stage IV melanoma. Patients had a treatment-limiting toxicity …