Diseases Commons^™

Distinct Hyperuricemia Trajectories Are Associated With Different Risks Of Incident Diabetes: A Prospective Cohort Study, Jia Liu, Huiying Pan, Yue Liu, Mengying Guan, Xia Li, Shuo Chen, Xingyao Tong, Yanxia Luo, Xiaonan Wang, Xinghua Yang, Xiuhua Guo, Jingbo Zhang, Lixin Tao

Research outputs 2022 to 2026

Background and aim: Conflicting results suggest a link between serum uric acid and diabetes and previous studies ignored the effect of continuous exposure of serum uric acid on diabetes risk. This study aims to characterize hyperuricemia trajectories in middle-aged adults and to examine its potential impact on diabetes risk, considering the role of obesity, dyslipidemia, and hypertension. Methods and results: The cohort included 9192 participants who were free of diabetes before 2013. The hyperuricemia trajectories during 2009–2013 were identified by latent class growth models. Incident diabetes during 2014–2018 was used as the outcome. Modified Poisson regression models were used to …

Reduced Peak Bone Mass In Young Adults With Low Motor Competence, Jocelyn Tan, Carrie Anne Ng, Nicolas H. Hart, Timo Rantalainen, Marc Sim, David Scott, Kun Zhu, Beth Hands, Paola Chivers

Research outputs 2022 to 2026

Although suboptimal bone health has been reported in children and adolescents with low motor competence (LMC), it is not known whether such deficits are present at the time of peak bone mass. We examined the impact of LMC on bone mineral density (BMD) in 1043 participants (484 females) from the Raine Cohort Study. Participants had motor competence assessed using the McCarron Assessment of Neuromuscular Development at 10, 14, and 17 years, and a whole-body dual-energy X-ray absorptiometry (DXA) scan at 20 years. Bone loading from physical activity was estimated from the International Physical Activity Questionnaire at the age of 17 …

First Presentation With Neuropsychiatric Symptoms In Autosomal Dominant Alzheimer's Disease: The Dominantly Inherited Alzheimer's Network Study, Antoinette O'Connor, Helen Rice, Josephine Barnes, Natalie S. Ryan, Kathy Y. Liu, Ricardo Francisco Allegri, Sarah Berman, John M. Ringman, Carlos Cruchaga, Martin R. Farlow, Jason Hassenstab, Jae-Hong Lee, Richard J. Perrin, Chengjie Xiong, Brian Gordon, Allan I. Levey, Alison Goate, Neil Graff-Radford, Johannes Levin, Mathias Jucker, Tammie Benzinger, Eric Mcdade, Hiroshi Mori, James M. Noble, Peter R. Schofield, Ralph N. Martins, Stephen Salloway, Jasmeer Chhatwal, John C. Morris, Randall Bateman, Rob Howard, Suzanne Reeves, Nick C. Fox

Research outputs 2022 to 2026

Behavioural changes and neuropsychiatric symptoms (NPS) commonly occur in Alzheimer’s disease (AD) but may not be recognised as AD-related when they are the presenting feature. NPS are important as they are associated with greater functional impairment, poorer quality of life, accelerated cognitive decline and worsened caregiver burden.1 Autosomal dominant AD (ADAD), although < 1% of total AD cases, provides a valuable opportunity to study the clinical heterogeneity of AD. The young age at onset reduces the prevalence of age-related comorbid pathologies and the near 100% penetrance of pathogenic mutations reduces the likelihood of misdiagnosis.2 Anxiety and depression commonly occur in ADAD family members, with increased levels of depression having been found among predementia female mutation carriers.3 Subsequent studies, however, have shown that anxiety and/or depression are common regardless of mutation status, occurring in almost one in three at-risk individuals, with one study reporting a higher rate of depression in non-carriers (17%) than asymptomatic carriers (5%).4 5 Despite the high frequency of NPS in ADAD families, relatively little is known about the proportion of ADAD cases who present with predominantly behavioural symptoms. Our aims were to assess the first reported clinical change in symptomatic ADAD, to compare presentations across genotypes, and to compare cognitive performance between behavioural and cognitive-led presentations.

Cardiovascular Disease, Muscle Function, And Long-Term Falls Risk: The Perth Longitudinal Study Of Ageing Women, Abadi K. Gebre, Marc Sim, Jack Dalla Via, Alexander J. Rodríguez, Kun Zhu, John T. Schousboe, Jonathan M. Hodgson, Catherine P. Bondonno, Richard L. Prince, Joshua R. Lewis

Research outputs 2022 to 2026

Background: A few cross-sectional studies have highlighted inconsistent associations between cardiovascular disease (CVD) and musculoskeletal conditions. We sought to investigate the relationship between clinical CVD including subtypes, compromised muscle function, as well as incident self-reported and injurious falls in older women. Materials and methods: 1431 community-dwelling older women (mean age ± SD; 75.2 ± 2.7 years) were included in over 14.5 years of a prospective study, the Perth Longitudinal Study of Ageing in Women. CVD (up to 18-years prior to the baseline visit) and injurious fall hospitalizations over 14.5 years were obtained from linked health records. Self-reported falls for five …

Short-Term Effects Of Carbon Monoxide On Morbidity Of Chronic Obstructive Pulmonary Disease With Comorbidities In Beijing, Zhiwei Li, Feng Lu, Mengmeng Liu, Moning Guo, Lixin Tao, Tianqi Wang, Mengyang Liu, Xiuhua Guo, Xiangtong Liu

Research outputs 2022 to 2026

The association between CO and chronic obstructive pulmonary disease (COPD) has been widely reported; however, the association among patients with type 2 diabetes mellitus (T2DM) or hypertension has remained largely unknown in China. Over-dispersed generalized additive model was adopted to quantity the associations between CO and COPD with T2DM or hypertension. Based on principal diagnosis, COPD cases were identified according to the International Classification of Diseases (J44), and a history of T2DM and hypertension was coded as E12 and I10-15, O10-15, P29, respectively. A total of 459,258 COPD cases were recorded from 2014 to 2019. Each interquartile range uptick in …

Editorial: Untangle The Broad Connections And Tight Interactions Between Human Microbiota And Complex Diseases Through Data-Driven Approaches, Liang Wang, Zuo-Bin Zhu, Li Zhang, Jian Li, Qi Zhao

Research outputs 2022 to 2026

It is well-known that microorganisms are ubiquitous in the environment and occupy almost all habitats in animals and humans (Finlay and Clarke, 1999; Rosenberg, 2021). Traditionally, microorganisms are studied as individuals grown in isolation under artificial conditions; however, with the development of experimental techniques and computational methods, microbes are now frequently considered as a functional group in a particular niche and studied at the community level in order to best mimicking the real-world situations (American Academy of Microbiology, 2004). During the study of microbial communities, two terms are commonly used, that is, microbiota and microbiome.

Measures Of Carotid Atherosclerosis And Fall-Related Hospitalization Risk: The Perth Longitudinal Study Of Ageing Women, Abadi K. Gebre, Marc Sim, Jack Dalla Via, Alexander J. Rodríguez, Jonathan M. Hodgson, Catherine P. Bondonno, Peter L. Thompson, Richard L. Prince, Joshua R. Lewis

Research outputs 2022 to 2026

Background and aims: We and others have identified links between cardiovascular conditions and poor musculoskeletal health. However, the relationship between measures of carotid atherosclerosis such as focal carotid plaque and common carotid intima media thickness (CCA-IMT) and falls remains understudied. This study examined the association between measures of carotid atherosclerosis and fall-related hospitalization over 11.5 years in community dwelling older women. Methods and results: 1116 older women recruited in 1998 to a five-year randomized controlled trial to examine the effect of calcium supplementation in preventing fracture and who had undertaken B-mode ultrasound in 2001 (three years after the baseline clinical …

Genetic Association And Causal Inference Between Lung Function And Venous Thromboembolism, Qiaoyun Zhang, Xiaoyu Zhang, Jie Zhang, Mengyang Jiang, Yiqiang Zhang, Deqiang Zheng, Lijuan Wu, Wei Wang, Baoguo Wang, Youxin Wang

Research outputs 2022 to 2026

Background: Previous studies have indicated that lower lung function is related to a higher risk of venous thromboembolism (VTE). However, causal inferences may be affected by confounders, coheritability or reverse causality. We aimed to explore the causal association between lung function and VTE. Methods: Summary data from public genome-wide association studies (GWAS) for lung function and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly related to exposure were filtered as proxy instruments. We adopted linkage disequilibrium score regression (LDSC) and two-sample Mendelian randomization (MR) analyses to infer the genetic backgrounds and causal …

What We Don't Need To Prove But Need To Do In Multidisciplinary Treatment And Care In Huntington's Disease: A Position Paper, Alzbeta Mühlbӓck, Marleen Van Walsem, Martha Nance, Astri Arnesen, Kirsty Page, Alexandra Fisher, Manon Van Kampen, Angela Nuzzi, Roy Limpert, Hanne Ludt Fossmo, Travis Cruickshank, Ruth Veenhuizen

Research outputs 2022 to 2026

Background: Huntington’s disease is a complex neurodegenerative hereditary disease with symptoms in all domains of a person’s functioning. It begins after a healthy start in life and leads through the relentless progression over many years to complete care dependency and finally death. To date, the disease is incurable. The long progressive complex nature of the disease demands multiple disciplines for treatment and care of patient and family. These health care providers need inter- and multidisciplinary collaboration to persevere and be efficacious in this devastating disease trajectory. Discussion: The position paper outlines current knowledge and experience alongside the experience and consensus …

Early Visual Alterations In Individuals At-Risk Of Alzheimer’S Disease: A Multidisciplinary Approach, Inés López-Cuenca, Alberto Nebreda, Alejandra García-Colomo, Elena Salobrar-García, Jaisalmer De Frutos-Lucas, Ricardo Bruña, Ana I. Ramírez, Federico Ramirez-Toraño, Juan J. Salazar, Ana Barabash, Pedro Gil, Fernando Maestú, José M. Ramírez, Rosa De Hoz

Research outputs 2022 to 2026

Background: The earliest pathological features of Alzheimer’s disease (AD) appear decades before the clinical symptoms. The pathology affects the brain and the eye, leading to retinal structural changes and functional visual alterations. Healthy individuals at high risk of developing AD present alterations in these ophthalmological measures, as well as in resting-state electrophysiological activity. However, it is unknown whether the ophthalmological alterations are related to the visual-related electrophysiological activity. Elucidating this relationship is paramount to understand the mechanisms underlying the early deterioration of the system and an important step in assessing the suitability of these measures as early biomarkers of disease. …

Temporal Relationship Between Atherogenic Dyslipidemia And Inflammation And Their Joint Cumulative Effect On Type 2 Diabetes Onset: A Longitudinal Cohort Study, Yulong Lan, Guanzhi Chen, Dan Wu, Xiong Ding, Zegui Huang, Xianxuan Wang, Lois Balmer, Xingang Li, Manshu Song, Wei Wang, Shouling Wu, Youren Chen

Research outputs 2022 to 2026

Background: Concurrent atherogenic dyslipidemia and elevated inflammation are commonly observed in overt hyperglycemia and have long been proposed to contribute to diabetogenesis. However, the temporal relationship between them and the effect of their cumulative co-exposure on future incident type 2 diabetes (T2D) remains unclear. Methods: Longitudinal analysis of data on 52,224 participants from a real-world, prospective cohort study (Kailuan Study) was performed to address the temporal relationship between high-sensitivity C-reactive protein (hsCRP) and the atherogenic index of plasma (AIP, calculated as triglyceride/high-density lipoprotein) in an approximately 4-year exposure period (2006/2007 to 2010/2011). After excluding 8824 participants with known diabetes, 43,360 …

Checkpoint Inhibitor Immune-Related Adverse Events: A Focused Review On Autoantibodies And B Cells As Biomarkers, Advancements And Future Possibilities, John Taylor, Aesha Gandhi, Elin Gray, Pauline Zaenker

Research outputs 2022 to 2026

The use of immune checkpoint inhibitors (ICIs) has evolved rapidly with unprecedented treatment benefits being obtained for cancer patients, including improved patient survival. However, over half of the patients experience immune related adverse events (irAEs) or toxicities, which can be fatal, affect the quality of life of patients and potentially cause treatment interruption or cessation. Complications from these toxicities can also cause long term irreversible organ damage and other chronic health conditions. Toxicities can occur in various organ systems, with common observations in the skin, rheumatologic, gastrointestinal, hepatic, endocrine system and the lungs. These are not only challenging to manage …

Consensus Guidelines For Sarcopenia Prevention, Diagnosis And Management In Australia And New Zealand, Jesse Zanker, Marc Sim, Kate Anderson, Saliu Balogun, Sharon L. Brennan-Olsen, Elsa Dent, Gustavo Duque, Christian M. Girgis, Mathis Grossmann, Alan Hayes, Tim Henwood, Vasant Hirani, Charles Inderjeeth, Sandra Iuliano, Justin Keogh, Joshua R. Lewis, Gordon S. Lynch, Julie A. Pasco, Steven Phu, Esmee M. Reijnierse, Nicholas Russell, Lara Vlietstra, Renuka Visvanathan, Troy Walker, Debra L. Waters, Solomon Yu, Andrea B. Maier, Robin M. Daly, David Scott

Research outputs 2022 to 2026

Background:

Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand.

Methods:

A four-phase modified Delphi process involving topic experts and informed …

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 …

Multimodal Exercise In Older Patients With Advanced Pancreatic Cancer Undergoing First-Line Chemotherapy: A Case Series Examining Feasibility And Preliminary Efficacy, Hao Luo, Daniel A. Galvão, Robert U. Newton, Colin I. Tang, Nigel Spry, Dennis R. Taaffe

Research outputs 2022 to 2026

Purpose. Exercise is emerging as an adjunct therapy to cancer treatment; however, its role in older patients with advanced pancreatic cancer undergoing first-line chemotherapy is unclear. The aim of this study was to primarily provide evidence on feasibility with an exploratory examination of the initial efficacy of exercise in this clinical setting.

Materials and Methods. Six patients aged 60–75 years with de novo or recurrent advanced pancreatic cancer undergoing first-line chemotherapy consented to participate in twice-weekly exercise that included resistance and aerobic training and boxing-related activities for up to 12 weeks. Patients were monitored for attendance, adherence, and …

How General Practitioners And Patients Discuss Type 2 Diabetes Mellitus And Cardiovascular Diseases Concerns During Consultations: Implications For Digital Health, Urvashi Rohilla, Jayashanthi P. Ramarao, Jared Lane, Neha N. Khatri, James Smith, Kathleen Yin, Annie Y. S. Lau

Research outputs 2022 to 2026

Objective: To analyse general practitioner–patient consultations about type 2 diabetes mellitus or cardiovascular diseases and describe (i) the nature of self-management discussions; (ii) actions required from patients during and after consultation regarding self-management; and (iii) implications for digital health to support patients during (and after) consultation. Method: This study screened 281 general practitioner consultations conducted in 2017 within the UK general practice setting from an existing dataset containing videos and transcripts of consultations between GPs and patients. Secondary analysis was conducted using a multi-method approach, including descriptive, content, and visualisation analysis, to inform the nature of self-management discussions, what actions …

Location Of Pathogenic Variants In Psen1 Impacts Progression Of Cognitive, Clinical, And Neurodegenerative Measures In Autosomal-Dominant Alzheimer's Disease, Stephanie A. Schultz, Zahra Shirzadi, Aaron P. Schultz, Lei Liu, Colleen D. Fitzpatrick, Eric Mcdade, Nicolas R. Barthelemy, Alan Renton, Bianca Esposito, Nelly Joseph-Mathurin, Carlos Cruchaga, Charles D. Chen, Alison Goate, Ricardo F. Allegri, Tammie L. S. Benzinger, Sarah Berman, Helena C. Chui, Anne M. Fagan, Martin R. Farlow, Nick C. Fox, Brian A. Gordon, Gregory S. Day, Neill R. Graff-Radford, Jason J. Hassenstab, Bernard J. Hanseeuw, Anna Hofmann, Clifford R. Jack Jr, Mathias Jucker, Celeste M. Karch, Robert A. Koeppe, Jae-Hong Lee, Allan I. Levey, Johannes Levin, Ralph Martins, Hiroshi Mori, John C. Morris, James Noble, Richard J. Perrin, Pedro Rosa-Neto, Stephen P. Salloway, Raquel Sanchez-Valle, Peter R. Schofield, Chengjie Xiong, Keith A. Johnson, Randall J. Bateman, Reisa A. Sperling, Jasmeer P. Chhatwal, Dominantly Inherited Alzheimer Network Investigators

Research outputs 2022 to 2026

Although pathogenic variants in PSEN1 leading to autosomal-dominant Alzheimer disease (ADAD) are highly penetrant, substantial interindividual variability in the rates of cognitive decline and biomarker change are observed in ADAD. We hypothesized that this interindividual variability may be associated with the location of the pathogenic variant within PSEN1. PSEN1 pathogenic variant carriers participating in the Dominantly Inherited Alzheimer Network (DIAN) observational study were grouped based on whether the underlying variant affects a transmembrane (TM) or cytoplasmic (CY) protein domain within PSEN1. CY and TM carriers and variant non-carriers (NC) who completed clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection …

Utility Of Dna Methylation As A Biomarker In Ageing And Alzheimer’S Disease, Lidija Milicic, Tenielle Porter, Michael Vacher, Simon M. Laws

Research outputs 2022 to 2026

Epigenetic mechanisms such as DNA methylation have been implicated in a number of diseases including cancer, heart disease, autoimmune disorders, and neurodegenerative diseases. While it is recognized that DNA methylation is tissue-specific, a limitation for many studies is the ability to sample the tissue of interest, which is why there is a need for a proxy tissue such as blood, that is reflective of the methylation state of the target tissue. In the last decade, DNA methylation has been utilized in the design of epigenetic clocks, which aim to predict an individual’s biological age based on an algorithmically defined set …

Physical Education And Covid-19: What Have We Learned?, Valeria Varea, Ana Riccetti, Gustavo González-Calvo, Marcela Siracusa, Alfonso García-Monge

Research outputs 2022 to 2026

The aim of this paper is to explore what we have learned during the COVID-19 pandemic in the field of Physical Education in three different countries: Argentina, Spain and Sweden. Data were generated through semi-structured interviews, and the concept of field agency is used to make sense of the data. Differences were found among the three countries, regarding the content of the classes, the use of resources, the emotions of teachers, and the use of physical contact. This was also a result of the regulations and resources in place. The COVID-19 pandemic has demonstrated that the nature of the field …

Externalizing Traits: Shared Causalities For Covid-19 And Alzheimer's Dementia Using Mendelian Randomization Analysis, Haotian Wang, Mingyang Cao, Yingjun Xi, Weijie Cao, Xiaoyu Zhang, Xiaoni Meng, Deqiang Zheng, Lijuan Wu, Wei Wang, Di Liu, Youxin Wang

Research outputs 2022 to 2026

Externalizing traits have been related with the outcomes of coronavirus disease 2019 (COVID-19) and Alzheimer's dementia (AD); however, whether these associations are causal remains unknown. We used the two-sample Mendelian randomization (MR) approach with more than 200 single-nucleotide polymorphisms (SNPs) for externalizing traits to explore the causal associations of externalizing traits with the risk of COVID-19 (infected COVID-19, hospitalized COVID-19, and severe COVID-19) or AD based on the summary data. The inverse variance–weighted method (IVW) was used to estimate the main effect, followed by several sensitivity analyses. IVW analysis showed significant associations of externalizing traits with COVID-19 infection (odds ratio …

Does Lower-Limb Osteoarthritis Alter Motor Cortex Descending Drive And Voluntary Activation? A Systematic Review And Meta-Analysis, Myles C. Murphy, Christopher Latella, Ebonie K. Rio, Janet L. Taylor, Stephanie Martino, Colin Sylvester, William Hale, Andrea B. Mosler

Research outputs 2022 to 2026

Purpose: The aim of the study was to quantify motor cortex descending drive and voluntary activation (VA) in people with lower-limb OA compared to controls. Methods: A systematic review and meta-analysis according to the PRISMA guidelines was carried out. Seven databases were searched until 30 December 2022. Studies assessing VA or responses to transcranial magnetic stimulation (TMS; i.e. motor evoked potential, intracortical facilitation, motor threshold, short-interval intracortical inhibition, and silent period) were included. Study quality was assessed using Joanna Briggs Institute criteria and evidence certainty using GRADE. The meta-analysis was performed using RevMan inverse variance, mixed-effect models. Results: Eighteen studies …

Impaired Muscle Function, Including Its Decline, Is Related To Greater Long-Term Late-Life Dementia Risk In Older Women, Simone Radavelli-Bagatini, Helen Macpherson, David Scott, Robin M. Daly, Jonathan M. Hodgson, Simon M. Laws, Kun Zhu, Richard L. Prince, Joshua R. Lewis, Marc Sim

Research outputs 2022 to 2026

Background: Impaired muscle function has been identified as a risk factor for declining cognitive function and cardiovascular health, both of which are risk factors for late-life dementia (after 80 years of age). We examined whether hand grip strength and timed-up-and-go (TUG) performance, including their change over 5 years, were associated with late-life dementia events in older women and whether any associations provided independent information to Apolipoprotein E ℇ4 (APOE ℇ4) genotype. Methods: Grip strength and TUG were assessed in community-dwelling older women (mean ± SD; age 75.0 ± 2.6 years) at baseline (n = 1225) and 5 years (n = …

Covid-19 In Western Australia: ‘The Last Straw’ And Hopes For A ‘New Normal’ For Parents Of Children With Long-Term Conditions, Stephanie Smith, Mary Tallon, James Smith, Lauren Jones, Evalotte Mörelius

Research outputs 2022 to 2026

Background: Children with long-term conditions are vulnerable due to the treatments required for their conditions. Since the start of the coronavirus disease 2019 (COVID-19) pandemic, Western Australians experienced restrictions that changed daily life activities but were able to return to some of their previous routines due to the restrictions. Aim: The study explored the stress experiences of parents caring for children with long-term conditions during COVID-19 in Western Australia. Design and Participants: The study was codesigned with a parent representative caring for children with long-term conditions to ensure essential questions were targeted. Twelve parents of children with various long-term conditions …

Two-Year Prognostic Utility Of Plasma P217+Tau Across The Alzheimer’S Continuum, A. Feizpour, V. Doré, J. D. Doecke, Z. S. Saad, G. Triana-Baltzer, R. Slemmon, P. Maruff, N. Krishnadas, P. Bourgeat, K. Huang, C. Fowler, S. R. Rainey-Smith, A. I. Bush, L. Ward, J. Robertson, R. N. Martins, C. L. Masters, V. L. Villemagne, J. Fripp, H. C. Kolb, C. C. Rowe

Research outputs 2022 to 2026

Background: Plasma p217+tau has shown high concordance with cerebrospinal fluid (CSF) and positron emission tomography (PET) measures of amyloid- (A ) and tau in Alzheimer’s Disease (AD). However, its association with longitudinal cognition and comparative performance to PET A and tau in predicting cognitive decline are unknown. Objectives: To evaluate whether p217+tau can predict the rate of cognitive decline observed over two-year average follow-up and compare this to prediction based on A (18F-NAV4694) and tau (18F-MK6240) PET. We also explored the sample size required to detect a 30% slowing in cognitive decline in a 2-year trial and selection test cost …

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 …

Corrigendum: Evolution, Ecology, And Zoonotic Transmission Of Betacoronaviruses: A Review, Herbert F. Jelinek, Mira Mousa, Eman Alefishat, Wael Osman, Ian Spence, Dengpan Bu, Samuel F. Feng, Jason Byrd, Paola A. Magni, Shafi Sahibzada, Guan K. Tay, Habiba S. Alsafar

Research outputs 2022 to 2026

In the published article, there was an error in the legend for Figure 1 as published. The figure legend did not indicate that it has been adapted from Plowright et al. (2017). Copyright permission was obtained from Springer Nature to adapt Figure 1 from Plowright et al. (2017). The corrected legend appears below. Figure 1. Zoonotic risk distribution, pathway to spillover, and the multimodal role of the determinants of spillover. The zoonotic risk is demonstrated by the accumulated distribution of reservoir hosts and vectors that play a role in the pathway to spillover. The risk of spillover is determined by …

Patterns And Implications Of Neurological Examination Findings In Autosomal Dominant Alzheimer Disease, Jonathan Vöglein, Nicolai Franzmeier, John C. Morris, Marianne Dieterich, Eric Mcdade, Mikael Simons, Oliver Preische, Anna Hofmann, Jason Hassenstab, Tammie L. Benzinger, Anne Fagan, James M. Noble, Sarah B. Berman, Neill R. Graff-Radford, Bernardino Ghetti, Martin R. Farlow, Jasmeer P. Chhatwal, Stephen Salloway, Chengjie Xiong, Celeste M. Karch, Nigel Cairns, Richard J. Perrin, Gregory Day, Ralph Martins, Raquel Sanchez-Valle, Hiroshi Mori, Hiroyuki Shimada, Takeshi Ikeuchi, Kazushi Suzuki, Peter R. Schofield, Colin L. Masters, Alison Goate, Virginia Buckles, Nick C. Fox, Patricio Chrem, Ricardo Allegri, John M. Ringman, Igor Yakushev, Christoph Laske, Mathias Jucker, Günter Höglinger, Randall L. Bateman, Adrian Danek, Johannes Levin, Dominantly Inherited Alzheimer Network

Research outputs 2022 to 2026

Introduction:

As knowledge about neurological examination findings in autosomal dominant Alzheimer disease (ADAD) is incomplete, we aimed to determine the frequency and significance of neurological examination findings in ADAD.

Methods:

Frequencies of neurological examination findings were compared between symptomatic mutation carriers and non mutation carriers from the Dominantly Inherited Alzheimer Network (DIAN) to define AD neurological examination findings. AD neurological examination findings were analyzed regarding frequency, association with and predictive value regarding cognitive decline, and association with brain atrophy in symptomatic mutation carriers.

Results:

AD neurological examination findings included abnormal deep tendon reflexes, gait disturbance, pathological cranial nerve examination findings, …

Prognostic And Predictive Value Of Metformin In The European Organisation For Research And Treatment Of Cancer 1325/Keynote-054 Phase Iii Trial Of Pembrolizumab Versus Placebo In Resected High-Risk Stage Iii Melanoma, Oliver J. Kennedy, Michal Kicinski, Sara Valpione, Sara Gandini, Stefan Suciu, Christian U. Blank, Georgina V. Long, Victoria G. Atkinson, Stéphane Dalle, Andrew M. Haydon, Andrey Meshcheryakov, Adnan Khattak, Matteo S. Carlino, Shahneen Sandhu, James Larkin, Susana Puig, Paolo A. Ascierto, Piotr Rutkowski, Dirk Schadendorf, Marye Boers-Sonderen, Anna M. Di Giacomo, Alfonsus J. M. Van Der Eertwegh, Jean-Jacques Grob, Ralf Gutzmer, Rahima Jamal, Alexander C. J. Van Akkooi, Caroline Robert, Alexander M. M. Eggermont, Paul Lorigan, Mario Mandala

Research outputs 2022 to 2026

Background: Metformin is a commonly prescribed and well-tolerated medication. In laboratory studies, metformin suppresses BRAF wild-type melanoma cells but accelerates the growth of BRAF-mutated cells. This study investigated the prognostic and predictive value of metformin, including with respect to BRAF mutation status, in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 randomised controlled trial. Methods: Patients with resected high-risk stage IIIA, IIIB, or IIIC melanoma received 200 mg of pembrolizumab (n = 514) or placebo (n = 505) every 3 weeks for twelve months. Pembrolizumab prolonged recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) at approximately 42 months …

Longitudinal Trajectories Of Basal Forebrain Volume In Normal Aging And Alzheimer's Disease, Ying Xia, Paul Maruff, Vincent Doré, Pierrick Bourgeat, Simon M. Laws, Christopher Fowler, Stephanie R. Rainey-Smith, Ralph N. Martins, Victor L. Villemagne, Christopher C. Rowe, Colin L. Masters, Elizabeth J. Coulson, Jurgen Fripp

Research outputs 2022 to 2026

Dysfunction of the cholinergic basal forebrain (BF) system and amyloid- (A ) deposition are early pathological features in Alzheimer's disease (AD). However, their association in early AD is not well-established. This study investigated the nature and magnitude of volume loss in the BF, over an extended period, in 516 older adults who completed A -PET and serial magnetic resonance imaging scans. Individuals were grouped at baseline according to the presence of cognitive impairment (CU, CI) and A status (A −, A +). Longitudinal volumetric changes in the BF and hippocampus were assessed across groups. The results indicated that high A …

Differential Dna Methylation Of Steatosis And Non-Alcoholic Fatty Liver Disease In Adolescence, Phillip E. Melton, M. A. Burton, K. A. Lillycrop, K. M. Godfrey, S. Rauschert, D. Anderson, G. C. Burdge, T. A. Mori, L. J. Beilin, O. T. Ayonrinde, J. M. Craig, John K. Olynyk, J. D. Holbrook, C. E. Pennell, W. H. Oddy, E. K. Moses, L. A. Adams, R. C. Huang

Research outputs 2022 to 2026

Background and aims:

Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks.

Approach and results:

We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at …