Publications by authors named "Melton P"

Background: Sex-differences in pain perception have been documented; however, the role of sex hormones in chronic musculoskeletal pain (CMP) remains unclear. Therefore, this study investigated whether sex hormones and sex hormone-binding globulin (SHBG) are associated with CMP.

Methods: We utilised data from the UK Biobank (n=357 424; females: 51.

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Introduction: Musculoskeletal pain typically occurs in multiple sites; however, no study has examined whether excessive visceral and subcutaneous adipose tissue are associated with musculoskeletal pain. This study therefore aimed to describe the associations between MRI-derived abdominal adipose tissue and multisite and widespread chronic musculoskeletal pain.

Methods: Data from the UK Biobank, a large prospective, population-based cohort study, were used.

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Spinal bone lesions encompass a wide array of pathologies, spanning from benign abnormalities to aggressive malignancies, such as diffusely localized metastases. Early detection and accurate differentiation of the underlying diseases is crucial for every patient's clinical treatment and outcome, with radiological imaging being a core element in the diagnostic pathway. Across numerous pathologies and imaging techniques, deep learning (DL) models are progressively considered a valuable resource in the clinical setting.

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After burn injury there is considerable variation in scar outcome, partially due to genetic factors. Scar vascularity is one characteristic that varies between individuals, and this study aimed to identify genetic variants contributing to different scar vascularity outcomes. An exome-wide array association study and gene pathway analysis was performed on a prospective cohort of 665 patients of European ancestry treated for burn injury, using their scar vascularity (SV) sub-score, part of the modified Vancouver Scar Scale (mVSS), as an outcome measure.

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Article Synopsis
  • - The study focuses on proliferative verrucous leukoplakia (PVL), a rare and aggressive condition that often turns into oral squamous cell carcinoma (OSCC), aiming to uncover genetic mutations involved in its progression.
  • - Researchers conducted whole exome sequencing on biopsies from patients diagnosed with PVL, finding mutations in several cancer-related genes and significant pathways like NOTCH and Hippo being commonly affected.
  • - The results point to both established and new potential mechanisms driving the cancerous changes seen in PVL, highlighting the importance of genetic analysis in understanding this condition.
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Burn injuries are devastating traumas, often leading to life-long consequences that extend beyond the observable burn scar. In the context of the nervous system, burn injury patients commonly develop chronic neurological disorders and have been suggested to have impaired motor cortex function, but the long-lasting impact on neurons and glia in the brain is unknown. Using a mouse model of non-severe burn injury, excitatory and inhibitory neurons in the primary motor cortex were labelled with fluorescent proteins using adeno-associated viruses (AAVs).

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Background: Women with a history of preeclampsia (PE) have been shown to have up to five times the risk of developing later-life cardiovascular disease (CVD). While PE and CVD are known to share clinical and molecular characteristics, there are limited studies investigating their shared genomics (genetics, epigenetics or transcriptomics) variation over time. Therefore, we sought to systematically review the literature to identify longitudinal studies focused on the genomic progression to CVD following PE.

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Understanding the biological mechanisms behind multimorbidity patterns in adolescence is important as they may act as intermediary risk factor for long-term health. We aimed to explore relationship between prenatal exposures and adolescent's psycho-cardiometabolic intermediary traits mediated through epigenetic biomarkers, using structural equation modeling (SEM). We used data from mother-child dyads from pregnancy and adolescents at 16-17 years from two prospective cohorts: Northern Finland Birth Cohort 1986 (NFBC1986) and Raine Study from Australia.

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Health care workers (n = 71) completed an online survey or participated in one of five focus groups. Clinical cutoff scores revealed concerning levels of depression (16%), anxiety, and burnout (49%). Qualitative responses (n = 172) yielded two themes: work environment and well-being.

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Article Synopsis
  • * A meta-analysis of 37 studies revealed that higher MEA is linked to different DNA methylation patterns in offspring at birth, childhood, and adolescence, with significant findings at 473 specific sites associated with maternal factors like smoking and nutrition.
  • * The research underscores the connection between socio-economic status and biological processes, enhancing our understanding of how maternal education impacts health through genetic mechanisms and emphasizing the role of social determinants in health disparities.
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Prostate cancer is one of the most commonly diagnosed cancers in men and unfortunately, disease will progress in up to a third of patients despite primary treatment. Currently, there is a significant lack of prognostic tests that accurately predict disease course; however, the acquisition of somatic chromosomal variation in the form of DNA copy number variants may help understand disease progression. Notably, studies have found that a higher burden of somatic copy number alterations (SCNA) correlates with more aggressive disease, recurrence after surgery and metastasis.

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Purpose: Modern digital teaching formats have become increasingly important in recent years, in part due to the COVID-19 pandemic. In January 2021, an online-based webinar series was established by the German Society for Radiation Oncology (DEGRO) and the young DEGRO (yDEGRO) working group. In the monthly 120-minute courses, selected lecturers teach curricular content as preparation for the board certification exam for radiation oncology.

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Objective: Dietary glycemic index (GI) and glycemic load (GL) are associated with cardiometabolic health in children and adolescents, with potential distinct effects in people with increased BMI. DNA methylation (DNAm) may mediate these effects. Thus, we conducted meta-analyses of epigenome-wide association studies (EWAS) between dietary GI and GL and blood DNAm of children and adolescents.

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The indirect contribution of multiple sclerosis (MS) relapses to disability worsening outcomes, and vice-versa, remains unclear. Disease modifying therapies (DMTs) are potential modulators of this association. Understanding how these endo-phenotypes interact may provide insights into disease pathogenesis and treatment practice in relapse-onset MS (ROMS).

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Aim: To investigate the impact of ablative fractional carbon dioxide laser (AFCOL) on patient-reported outcomes measures, subjective scar appearance, dermal architecture, and gene transcription in early burn scars.

Methods: Fifteen adult patients with a burn-related scar were recruited. Inclusion criteria were two non-contiguous scar areas of 1% total body surface area, similar baseline Vancouver scar scale (VSS) score and 3months since the time of injury.

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Article Synopsis
  • Childhood adversity affects DNA methylation patterns, potentially changing health outcomes throughout development, particularly during sensitive periods.
  • The study looked at data from the Avon Longitudinal Study of Parents and Children, focusing on various types of childhood adversity and its impact on DNA methylation at age 15.
  • Using structured life course modeling, researchers evaluated how timing, accumulation, and recency of adversity influence adolescent DNA methylation and aimed to replicate findings with other studies.
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Background: Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns.

Methods: We meta-analysed epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates.

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Aim: Investigate if childhood measures of sleep health are associated with epigenetic age acceleration in late adolescence.

Methods: Parent-reported sleep trajectories from age 5 to 17, self-reported sleep problems at age 17, and six measures of epigenetic age acceleration at age 17 were studied in 1192 young Australians from the Raine Study Gen2.

Results: There was no evidence for a relationship between the parent-reported sleep trajectories and epigenetic age acceleration (p ≥ 0.

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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.

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Limited studies have been conducted to identify and validate multiple sclerosis (MS) genetic loci associated with disability progression. We aimed to identify MS genetic loci associated with worsening of disability over time, and to develop and validate ensemble genetic learning model(s) to identify people with MS (PwMS) at risk of future worsening. We examined associations of 208 previously established MS genetic loci with the risk of worsening of disability; we learned ensemble genetic decision rules and validated the predictions in an external dataset.

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Scarring is a lifelong consequence of skin injury, with scar stiffness and poor appearance presenting physical and psychological barriers to a return to normal life. Lysyl oxidases are a family of enzymes that play a critical role in scar formation and maintenance. Lysyl oxidases stabilize the main component of scar tissue, collagen, and drive scar stiffness and appearance.

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We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts.

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Clinical and biomarker phenotypic associations for carriers of protein function-altering variants may help to elucidate gene function and health effects in populations. We genotyped 1127 Strong Heart Family Study participants for protein function-altering single nucleotide variants (SNV) and indels selected from a low coverage whole exome sequencing of American Indians. We tested the association of each SNV/indel with 35 cardiometabolic traits.

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Advances in genome sequencing technologies have unlocked new possibilities in identifying disease-associated and causative genetic markers, which may in turn enhance disease diagnosis and improve prognostication and management strategies. With the capability of examining genetic variations ranging from single-nucleotide mutations to large structural variants, whole-genome sequencing (WGS) is an increasingly adopted approach to dissect the complex genetic architecture of neurologic diseases. There is emerging evidence for different structural variants and their roles in major neurologic and neurodevelopmental diseases.

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