Publications by authors named "G.M. Thomas"

Rationale And Objective: Conventional positron emission tomography (PET) respiratory gating utilizes a fraction of acquired PET counts (i.e., optimal gate [OG]), whereas elastic motion correction with deblurring (EMCD) utilizes all PET counts to reconstruct motion-corrected images without increasing image noise.

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  • The study aims to investigate how early assessment and genetic counseling in a multidisciplinary Cardiomyopathy Clinic can enhance patient outcomes and reduce the severity of heart failure.
  • A total of 421 patients with various types of cardiomyopathy participated, with a significant portion undergoing genetic testing that revealed a notable incidence of pathogenic variants.
  • Follow-up showed increased use of heart failure medications and improved heart function, indicated by a rise in left ventricular ejection fraction (LVEF) and a decrease in left ventricular mass index (LVMI) among patients with dilated cardiomyopathy (DCM).
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  • The study examines the outcomes of cryoballoon-ablation for atrial fibrillation in women, focusing on those with heart failure with preserved ejection fraction (HFpEF) compared to those without.
  • Women with HFpEF displayed worse health indicators, including higher left atrial volume, increased left ventricular mass, reduced walking distances, and higher left atrial pressures.
  • Results showed that women with HFpEF had more frequent hospitalizations due to AF and did not experience significant improvements in heart failure symptoms or quality of life after the procedure, suggesting they represent a high-risk group.
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We report the discovery of an imidazopyridine series of IRAK1/4/pan-FLT3 kinase inhibitors. Optimization of this series has produced compound which displays potent and selective inhibition of IRAK1, IRAK4, FLT3, and all mutant forms of FLT3, as well as good in vitro ADME and pharmacokinetic properties. In a mouse xenograft model of AML, produces survival prolongation equal to that of Gilteritinib, the leading marketed FLT3 inhibitor currently used to treat AML.

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  • Immune checkpoint inhibitors, a type of cancer treatment, can cause serious side effects, including immune-related myocarditis (irMyocarditis), which can be fatal.
  • Researchers studied immune responses in the heart, tumor, and blood of 28 patients with irMyocarditis using advanced techniques like single-cell RNA sequencing and T-cell receptor (TCR) sequencing.
  • Their findings showed an increase in certain immune cells in the heart tissue of irMyocarditis patients and identified specific TCR clones associated with severe cases, shedding light on the disease's biology and potential biomarkers.
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Background: There is increasing evidence that air pollution and noise may have detrimental psychological impacts, but there are few studies evaluating adolescents, ground-level ozone exposure, multi-exposure models, or metrics beyond outdoor residential exposure. This study aimed to address these gaps.

Methods: Annual air pollution and traffic noise exposure at home and school were modelled for adolescents in the Greater London SCAMP cohort (N=7555).

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  • * Data from 670 patients revealed that while IVT may improve some outcomes, such as higher chances of achieving a modified Rankin Scale score of 0-2 in univariable analysis, this benefit was not consistently observed in more rigorous multivariable analyses.
  • * Overall, the findings suggest that adjunctive IVT may not significantly enhance clinical outcomes or safety compared to MT alone for this patient population.
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Objective: In the current exploratory study we estimate comorbidity rates between FDs [fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and irritable bowel syndrome (IBS)]-and IDs-[major depressive disorder (MDD) and generalized anxiety disorder (GAD)] by using self-reported diagnostic criteria.

Method: We analyzed data from 107,849 participants (mean age = 49.3 (SD = 13.

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  • Acute lymphoblastic leukemia (γδ T-ALL) is a rare and complex condition in children, prompting a study of 200 pediatric cases to identify its clinical and genetic characteristics.
  • The research revealed that very young children (under 3 years) with γδ T-ALL face a significantly high risk and display specific genetic changes, particularly involving STAG2 inactivation and LMO2 activation.
  • Importantly, their findings suggest that targeting DNA repair pathways linked to STAG2 inactivation with specific drugs could offer new treatment options and help classify patients based on their risk levels.
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Background And Aim: There are few long-term studies of respiratory health effects of landscape fires, despite increasing frequency and intensity due to climate change. We investigated the association between exposure to coal mine fire PM and fractional exhaled nitric oxide (FeNO) concentration 7.5 years later.

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5q-associated spinal muscular atrophy (SMA) is a motoneuron disease caused by mutations in the survival motor neuron 1 (SMN1) gene. Adaptive immunity may contribute to SMA as described in other motoneuron diseases, yet mechanisms remain elusive. Nusinersen, an antisense treatment, enhances SMN2 expression, benefiting SMA patients.

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  • Immune checkpoint inhibitor (ICI) therapy has significantly advanced cancer treatment but is often complicated by immune-related adverse events like checkpoint inhibitor colitis (irColitis).
  • A study profiling around 300,000 cells from patients with irColitis uncovered key immune cell expansions and molecular changes in the colon mucosa and blood, highlighting the complexity of the condition.
  • Findings indicate that specific T cells and epithelial interactions are crucial for understanding irColitis and may lead to new therapeutic approaches for managing this side effect of ICI therapy.
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Peripheral T cell lymphomas are typically aggressive with a poor prognosis. Unlike other hematologic malignancies, the lack of target antigens to discriminate healthy from malignant cells limits the efficacy of immunotherapeutic approaches. The T cell receptor expresses one of two highly homologous chains [T cell receptor β-chain constant (TRBC) domains 1 and 2] in a mutually exclusive manner, making it a promising target.

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Background: As the number and longevity of childhood cancer survivors increases, assessing treatment-associated late effects remains crucial. We longitudinally examined the incidence of and associated risk factors for Leydig cell dysfunction (LCD) and Leydig cell failure (LCF) in men treated for pediatric cancers at our institution.

Procedure: We performed a retrospective longitudinal cohort study of adult male survivors treated for various childhood cancers who are at risk for LCD.

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Purpose: Gamma delta T-cell receptor-positive acute lymphoblastic leukemia (γδ T-ALL) is a high-risk but poorly characterized disease.

Methods: We studied clinical features of 200 pediatric γδ T-ALL, and compared the prognosis of 93 cases to 1,067 protocol-matched non-γδ T-ALL. Genomic features were defined by transcriptome and genome sequencing.

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Introduction: Frailty is conventionally diagnosed using clinical tests and self-reported assessments. However, digital health technologies (DHTs), such as wearable accelerometers, can capture physical activity and gait during daily life, enabling more objective assessments. In this study, we assess the feasibility of deploying DHTs in community-dwelling older individuals, and investigate the relationship between digital measurements of physical activity and gait in naturalistic environments and participants' frailty status, as measured by conventional assessments.

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Cell therapies have yielded durable clinical benefits for patients with cancer, but the risks associated with the development of therapies from manipulated human cells are understudied. For example, we lack a comprehensive understanding of the mechanisms of toxicities observed in patients receiving T cell therapies, including recent reports of encephalitis caused by reactivation of human herpesvirus 6 (HHV-6). Here, through petabase-scale viral genomics mining, we examine the landscape of human latent viral reactivation and demonstrate that HHV-6B can become reactivated in cultures of human CD4 T cells.

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Cancer genomes from patients with African (AFR) ancestry have been poorly studied in clinical research. We leverage two large genomic cohorts to investigate the relationship between genomic alterations and AFR ancestry in six common cancers. Cross-cancer type associations, such as an enrichment of MYC amplification with AFR ancestry in lung, breast, and prostate cancers, and depletion of BRAF alterations are observed in colorectal and pancreatic cancers.

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Skeletal muscle adaptation to external stimuli, such as regeneration following injury and hypertrophy in response to resistance exercise, are blunted with advanced age. The accumulation of senescent cells, along with defects in myogenic progenitor cell (MPC) proliferation, have been strongly linked as contributing factors to age-associated impairment in muscle adaptation. p53 plays an integral role in all these processes, as upregulation of p53 causes apoptosis in senescent cells and prevents mitotic catastrophe in MPCs from old mice.

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Background And Objectives: Predicting neurodevelopmental outcome for neonates with hypoxic-ischemic encephalopathy (HIE) is important for clinical decision-making, care planning, and parent communication. We examined the relationship between EEG background and neurodevelopmental outcome among children enrolled in a trial of erythropoietin or placebo for neonates with HIE treated with therapeutic hypothermia.

Methods: Participants had EEG recorded throughout hypothermia.

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Background: Asian Indians are at higher risk of cardiometabolic disease compared to other ethnic groups, and the age of onset is typically younger. Cardiac structure and function are poorly characterized in this ethnic group. In this study, we describe image-acquisition methods and the reproducibility of measurements and detailed echocardiography characteristics in two large Indian population-based cohorts (the New Delhi and Vellore Birth Cohorts) from India.

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  • - The study aimed to find echocardiographic markers that can differentiate between different causes of increased left ventricular (LV) wall thickness, particularly cardiac amyloidosis (CA) and Anderson-Fabry disease (AFD), compared to hypertensive heart disease (HHT).
  • - Researchers evaluated echocardiographic data from 209 patients, assessing various parameters such as LV mass index, LV global longitudinal strain, and diastolic function measurements across the three conditions.
  • - Results showed that CA and AFD had significantly different echocardiographic profiles compared to HHT, with CA showing the lowest strain measurements and most impaired diastolic function, indicating distinct phenotypes that can aid in diagnosis and management.
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Background: Open circuit aerosol therapy is associated with the potential for fugitive emissions of medical aerosol. Various nebulisers and interfaces are used in respiratory treatments, including the recent consideration of filtered interfaces. This study aims to quantify fugitive medical aerosols from various nebuliser types, in conjunction with different filtered and non-filtered interfaces.

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Muscle-specific kinase (MuSK) is crucial for acetylcholine receptor (AChR) clustering and thereby neuromuscular junction (NMJ) function. NMJ dysfunction is a hallmark of several neuromuscular diseases, including MuSK myasthenia gravis. Aiming to restore NMJ function, we generated several agonist monoclonal antibodies targeting the MuSK Ig-like 1 domain.

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Background And Purpose: Few persons with Parkinson disease (PD) appear to engage in moderate-intensity walking associated with disease-modifying health benefits. How much time is spent walking at lower, yet still potentially beneficial, intensities is poorly understood. The purpose of this exploratory, observational study was to describe natural walking intensity in ambulatory persons with PD.

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