Medicine and Health Sciences Commons^™

Heritability Enrichment Of Immunoglobulin G N-Glycosylation In Specific Tissues, Xingang Li, Hao Wang, Yahong Zhu, Weijie Cao, Song Manshu, Youxin Wang, Haifeng Hou, Minglin Lang, Xiuhua Guo, Xuerui Tan, Jingdong J. Han, Wei Wang

Research outputs 2014 to 2021

Genome-wide association studies (GWAS) have identified over 60 genetic loci associated with immunoglobulin G (IgG) N-glycosylation; however, the causal genes and their abundance in relevant tissues are uncertain. Leveraging data from GWAS summary statistics for 8,090 Europeans, and large-scale expression quantitative trait loci (eQTL) data from the genotype-tissue expression of 53 types of tissues (GTEx v7), we derived a linkage disequilibrium score for the specific expression of genes (LDSC-SEG) and conducted a transcriptome-wide association study (TWAS). We identified 55 gene associations whose predicted levels of expression were significantly associated with IgG N-glycosylation in 14 tissues. Three working scenarios, i.e., tissue-specific, …

Pd-L1 Expression On Circulating Tumor Cells May Be Predictive Of Response To Pembrolizumab In Advanced Melanoma: Results From A Pilot Study, Muhammad K. Khattak, Anna L. Reid, James Freeman, Michelle Pereira, Ashleigh Mcevoy, Johnny Lo, Markus Frank, Tarek Meniawy, Ali Didan, Isaac Spencer, Benhur Amanuel, Michael Millward, Mel Ziman, Elin Gray

Research outputs 2014 to 2021

BACKGROUND: PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab.

METHODS: Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6-12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD-L1.

RESULTS: CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD-L1

CONCLUSION: Our results reveal the potential of …

Eftilagimod Alpha, A Soluble Lymphocyte Activation Gene-3 (Lag-3) Protein Plus Pembrolizumab In Patients With Metastatic Melanoma, Victoria Atkinson, Adnan Khattak, Andrew Haydon, Melissa Eastgate, Amitesh Roy, Prashanth Prithviraj, Christian Mueller, Chrystelle Brignone, Frederic Triebel

Research outputs 2014 to 2021

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, in combination with the programmed cell death-1 (PD-1) antagonist pembrolizumab. METHODS: The study was divided into two parts; parts A and B, where part A was the dose escalation part and part B was an extension part of the study. Patients with metastatic melanoma were treated with efti plus the standard dose of pembrolizumab. Blood samples were assayed to determine …

The Prognostic Impact Of Circulating Tumour Dna In Melanoma Patients Treated With Systemic Therapies—Beyond Braf Mutant Detection, Gabriela Marsavela, Peter A. Johansson, Michelle R. Pereira, Ashleigh C. Mcevoy, Anna L. Reid, Cleo Robinson, Lydia Warburton, Muhammad A. Khattak, Tarek M. Meniawy, Benhur Amanuel, Michael Millward, Nicholas K. Hayward, Melanie R. Ziman, Elin S. Gray, Leslie Calapre

Research outputs 2014 to 2021

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. In this study, we evaluated the predictive value of circulating tumour DNA (ctDNA) to inform therapeutic outcomes in metastatic melanoma patients receiving systemic therapies. We analysed 142 plasma samples from metastatic melanoma patients prior to commencement of systemic therapy: 70 were treated with BRAF/MEK inhibitors and 72 with immunotherapies. Patient-specific droplet digital polymerase chain reaction assays were designed for ctDNA detection. Plasma ctDNA was detected in 56% of patients prior to first-line anti-PD1 and/or anti-CTLA-4 treatment. The detection rate in the immunotherapy cohort was comparably lower than those with BRAF inhibitors …

Population-Based Case-Control Study Revealed Metabolomic Biomarkers Of Suboptimal Health Status In Chinese Population—Potential Utility For Innovative Approach By Predictive, Preventive, And Personalized Medicine, Hao Wang, Qiuyue Tian, Jie Zhang, Hongqi Liu, Xiaoyu Zhang, Weijie Cao, Jinxia Zhang, Enoch Odame Anto, Xingang Li, Xueqing Wang, Di Liu, Yulu Zheng, Zheng Guo, Lijuan Wu, Manshu Song, Youxin Wang, Wei Wang

Research outputs 2014 to 2021

Background: Suboptimal health status (SHS) is a subclinical stage of chronic diseases, and the identification of SHS provides an opportunity for the predictive, preventive, and personalized medicine (PPPM) of chronic diseases. Previous studies have reported the associations between metabolic signatures and early signs of chronic diseases. Methods: This study aimed to detect the metabolic biomarkers for the identification of SHS in a case-control study. SHS questionnaire-25 (SHSQ-25) was used in a population-based health survey to measure the SHS levels of participants. The liquid chromatography-mass spectrometry-based untargeted metabolomics analysis was conducted on plasma samples collected from 50 SHS participants and 50 …

No Causal Effect Of Telomere Length On Ischemic Stroke And Its Subtypes: A Mendelian Randomization Study, Weijie Cao, Xingang Li, Xiaoyu Zhang, Jie Zhang, Qi Sun, Xizhu Xu, Ming Sun, Qiuyue Tian, Qihuan Li, Hao Wang, Jiaonan Liu, Xiaoni Meng, Lijuan Wu, Manshu Song, Haifeng Hou, Youxin Wang, Wei Wang

Research outputs 2014 to 2021

Background: Epidemiological studies observing inconsistent associations of telomere length (TL) with ischemic stroke (IS) are susceptible to bias according to reverse causation and residual confounding. We aimed to assess the causal association between TL, IS, and the subtypes of IS, including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES) by performing a series of two-sample Mendelian randomization (MR) approaches. Methods: Seven single nucleotide polymorphisms (SNPs) were involved as candidate instrumental variables (IVs), summarized from a genome-wide meta-analysis including 37,684 participants of European descent. We analyzed the largest ever genome-wide association studies of stroke in Europe from …

Is The Blood An Alternative For Programmed Cell Death Ligand 1 Assessment In Non-Small Cell Lung Cancer?, Emmanuel Acheampong, Isaac Spencer, Weitao Lin, Melanie Ziman, Michael Millward, Elin Gray

Research outputs 2014 to 2021

Anti-programmed cell death (PD)-1/PD-ligand 1 (L1) therapies have significantly improved the outcomes for non-small cell lung cancer (NSCLC) patients in recent years. These therapies work by reactivating the immune system and enabling it to target cancer cells once more. There is a general agreement that expression of PD-L1 on tumour cells predicts the therapeutic response to PD-1/PD-L1 inhibitors in NSCLC. Hence, immunohistochemical staining of tumour tissue biopsies from NSCLC patients with PD-L1 antibodies is the current standard used to aid selection of patients for treatment with anti-PD-1 as first line therapy. However, issues of small tissue samples, tissue heterogeneity, the …

Validation Of Type 2 Diabetes Risk Variants Identified By Genome-Wide Association Studies In Northern Han Chinese, Ping Rao, Yong Zhou, Siqi Ge, Anxin Wang, Xinwei Yu, Mohamed Ali Alzain, Andrea K. Veronica, Jing Qiu, Manshu Song, Jie Zhang, Hao Wang, Honghong Fang, Qing Gao, Youxin Wang, Wei Wang

Research outputs 2014 to 2021

Background:

More than 60 genetic susceptibility loci associated with type 2 diabetes mellitus (T2DM) have been established in populations of Asian and European ancestry. Given ethnic differences and environmental factors, validation of the effects of genetic risk variants with reported associations identified by Genome-Wide Association Studies (GWASs) is essential. The study aims at evaluating the associations of T2DM with 29 single nucleotide polymorphisms (SNPs) from 19 candidate genes derived from GWASs in a northern Han Chinese population.

Method:

In this case-control study, 461 T2DM-diagnosed patients and 434 controls were recruited at the Jidong oil field hospital (Hebei, China) from January …

Galvanic Skin Response In Mood Disorders: A Critical Review, Roisin Vahey, Rodrigo Becerra

Research outputs 2014 to 2021

To critically review the literature on Galvanic Skin Response (GSR) within Mood Disorder populations. GSR profiles were examined for the various types of Mood Disorder and their association with comorbidity, suicidality and predispositions. This review examined studies with emotional and non-emotional stimuli whilst aiming to identify a Mood Disorder GSR profile by comparisons with healthy controls and other psychological or physical disorders. A systematic search for relevant literature was conducted using PsychINFO, CINAHL and MEDLINE databases. Studies using emotional stimuli to measure GSR in mood disorder patients were included. Some studies did not use emotional stimuli, however were included as …

Higher Breakfast Glycaemic Load Is Associated With Increased Metabolic Syndrome Risk, Including Lower Hdl-Cholesterol Concentrations And Increased Tag Concentrations, In Adolescent Girls, Analise Nicholl, Mary Du Heaume, Trevor A. Mori, Lawrence J. Beilin, Wendy H. Oddy, Alexandra P. Bremner, Therese A. O'Sullivan

Research outputs 2014 to 2021

Almost all previous studies examining the associations between glycaemic load (GL) and metabolic syndrome risk have used a daily GL value. The daily value does not distinguish between peaks of GL intake over the day, which may be more closely associated with the risk of the metabolic syndrome. The aim of the present study was to investigate the cross-sectional associations between daily and mealtime measures of GL and metabolic syndrome risk, including metabolic syndrome components, in adolescents. Adolescents participating in the 14-year follow-up of the Western Australian Pregnancy Cohort (Raine) Study completed 3 d food records and metabolic assessments. Breakfast …