Publications by authors named "John Day"

Expansion microscopy (ExM) enables nanoscale imaging using a standard confocal microscope through the physical, isotropic expansion of fixed immunolabeled specimens. ExM is widely employed to image proteins, nucleic acids, and lipid membranes in single cells; however, current methods limit the number of samples that can be processed simultaneously. We developed High-throughput Expansion Microscopy (HiExM), a robust platform that enables expansion microscopy of cells cultured in a standard 96-well plate.

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  • The study aimed to evaluate how otitis media with effusion (OME) progresses in children under 12 who do not have hearing loss.
  • Nineteen observational studies were analyzed, revealing that the resolution rates of OME varied widely over time, from 10% to 99% by 12 months, with significant differences based on the population and the criteria for resolution.
  • Although there was a trend of improved resolution and recurring cases over longer follow-up, the results did not show a consistent pattern, indicating that varied populations and definitions played a role.
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  • Spinal muscular atrophy (SMA) is a genetic disorder resulting from mutations in the SMN1 gene, with a study aiming to track changes in motor function over 4 years using the Hammersmith Functional Motor Scale Expanded (HFMSE).
  • The research involved analyzing data from multiple countries, focusing on factors like age, functional status, and the number of SMN2 gene copies in SMA types II and III.
  • Results showed SMA type II patients had a mean decline of -2.20 points, while type III experienced a -2.75 point decline over 4 years, with age and baseline scores being significant predictors of these changes, suggesting the need for detailed assessment in specific SMA subgroups.
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Raman spectroscopy of muscle provides a molecular fingerprint to identify the disease. Previous work has demonstrated effectiveness in differentiating between two groups of equal sizes (e.g.

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Objective: To systematically assess the modifiable risk factors for developing otitis media with effusion (OME) in children under 12 years.

Methods: We searched Embase, MEDLINE, INAHTA database, CENTRAL, CDSR and Epistemonikos for cohort studies with ≥40 children per arm/prognostic factor, published in English from 2000 to November 2022. We assessed risk of bias using the Quality in Prognosis Studies checklist, and overall evidence quality was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

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The Revised upper limb module (RULM) has been increasingly used in clinical trials and in clinical settings. The aim of this study was to use the 'shift analysis' to assess the patterns of lost or gained abilities for each item on the RULM in an untreated cohort, stratified by SMA type, age, SMN2 copy number, and motor functional status. The analysis was performed on 222 12-month paired assessments from 129 individuals (115 assessment from type II and 107 from type III) who had at least two assessments at yearly intervals.

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  • The objective of the study was to evaluate the natural history of hearing loss related to otitis media with effusion (OME) in children under 12 years old.
  • A comprehensive search of multiple medical databases identified 13 relevant studies involving different sample sizes that examined the resolution rates of OME-related hearing loss over time.
  • Results showed that while OME-related hearing loss resolution improved significantly over longer follow-up periods, the rates varied considerably based on the duration of OME and the specific population studied, indicating a complex relationship and varying definitions of resolution.
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Alpha emitters like plutonium pose severe health risks when ingested, damaging DNA and potentially causing cancer. Traditional detection methods require proximity within millimeters of the contamination source, presenting safety risks and operational inefficiencies. Long-range detection through alpha radioluminescence (RL) offers a promising alternative.

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  • At 12 months, apitegromab showed improved motor function and a favorable safety profile in patients with Type 2 or 3 spinal muscular atrophy (SMA); this study reports on the extended effects after 36 months for nonambulatory patients.
  • In the open-label extension of the study, 35 nonambulatory patients received apitegromab and were evaluated using various assessments, resulting in significant improvements in motor scores and caregiver-reported outcomes over 36 months.
  • The positive effects of apitegromab observed at 12 months were maintained at 36 months, with common side effects including fever, nasopharyngitis, and respiratory infections, but no new safety concerns were identified. *
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Several studies have shown the efficacy of new disease-modifying therapies in slowing down type II SMA progression using the Hammersmith Functional Motor Scale Expanded (HFMSE). This research aims to enhance understanding of activity changes across age groups post-nusinersen treatment using shift analysis, compared with untreated individuals. Retrospective data from the, international SMA consortium (iSMAc) dataset were analyzed, assessing individual item changes over 12 months.

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Background And Objectives: Nusinersen has shown significant functional motor benefit in the milder types of spinal muscular atrophy (SMA). Less is known on the respiratory outcomes in patients with nusinersen-treated SMA. The aim of this study was to describe changes in respiratory function in pediatric patients with SMA type 2 and 3 on regular treatment with nusinersen within the iSMAc international cohort and to compare their trajectory with the natural history (NH) data published by the consortium in 2020.

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Heavy nuclides like uranium and their decay products are commonly found in nuclear industries and can pose a significant health risk to humans due to their alpha-emitting properties. Traditional alpha detectors require close contact with the contaminated surface, which can be time-consuming, labour-intensive, and put personnel at risk. Remote detection is urgently needed but very challenging.

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  • The study investigates the effects of joint hypermobility (JH) on function in individuals with spinal muscular atrophy (SMA), highlighting the common occurrence of muscle weakness and contractures.
  • A significant majority (86%) of participants exhibited at least one hypermobile joint, with specific correlations found between JH in hip extension and overall function scores, as well as between ankle plantar flexion and walking distance.
  • The findings suggest that understanding the relationship between lower-limb range of motion and function is crucial for enhancing future rehabilitation approaches for those with SMA.
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Soil organic carbon (SOC) is a soil health indicator and understanding dynamics changing SOC stocks will help achieving net zero goals. Here we present four datasets featuring 11,750 data points covering co-located aboveground and below-ground metrics for exploring ecosystem SOC dynamics. Five sites across England with an established land use contrast, grassland and woodland next to each other, were rigorously sampled for aboveground (n = 109), surface (n = 33 soil water release curves), topsoil, and subsoil metrics.

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Background And Purpose: Spinal muscular atrophy (SMA) is a rare and progressive neuromuscular disorder with varying severity levels. The aim of the study was to calculate minimal clinically important difference (MCID), minimal detectable change (MDC), and values for the Hammersmith Functional Motor Scale Expanded (HFMSE) in an untreated international SMA cohort.

Methods: The study employed two distinct methods.

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Neuromuscular disorders are a group of conditions that can result in weakness of skeletal muscles. Examples include fatal diseases such as amyotrophic lateral sclerosis and conditions associated with high morbidity such as myopathies (muscle diseases). Many of these disorders are known to have abnormal protein folding and protein aggregates.

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Raman spectroscopy shows promise as a biomarker for complex nerve and muscle (neuromuscular) diseases. To maximise its potential, several challenges remain. These include the sensitivity to different instrument configurations, translation across preclinical/human tissues and the development of multivariate analytics that can derive interpretable spectral outputs for disease identification.

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Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder characterised by progressive motor function decline. Motor function is assessed using several functional outcome measures including the Revised Hammersmith Scale (RHS).

Objective: In this study, we present longitudinal trajectories for the RHS in an international cohort of 149 untreated paediatric SMA 2 and 3 patients (across 531 assessments collected between March 2015 and July 2019).

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Background And Objectives: Currently approved therapies for spinal muscular atrophy (SMA) reverse the degenerative course, leading to better functional outcome, but they do not address the impairment arising from preexisting neurodegeneration. Apitegromab, an investigational, fully human monoclonal antibody, inhibits activation of myostatin (a negative regulator of skeletal muscle growth), thereby preserving muscle mass. The phase 2 TOPAZ trial assessed the safety and efficacy of apitegromab in individuals with later-onset type 2 and type 3 SMA.

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Objective: Authors evaluated the performance of a commercially available next-generation sequencing assay kit; this was based on genomic content from Illumina's TruSight™ Oncology 500 research assay that identifies BRCA variants and proprietary algorithms licensed from Myriad and, with additional genomic content, measures the homologous recombination deficiency (HRD) genomic instability score (GIS) in tumor tissue (TSO 500 HRD assay).

Methods: Data from the TSO 500 HRD assay were compared with data from the Myriad MyChoice®CDx PLUS assay (Myriad assay). Prevalence rates for overall HRD status and BRCA mutations (a deleterious or suspected deleterious BRCA1 or BRCA2 mutation or both) and assay agreement rates for HRD GIS and BRCA analysis were assessed in ovarian tumor samples.

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  • Long-term real-world data on the effectiveness and safety of onasemnogene abeparvovec for spinal muscular atrophy (SMA) is crucial for understanding outcomes outside clinical trials.
  • The RESTORE registry tracked 168 patients treated with this therapy, revealing a median age of 3 months at treatment and a majority identified through newborn screening.
  • Results showed all patients maintained or achieved motor milestones, but nearly half experienced at least one adverse event, reinforcing the treatment's safety profile.
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Assessing endurance in non-ambulatory individuals with Spinal Muscular Atrophy (SMA) has been challenging due to limited evaluation tools. The Assisted 6-Minute Cycling Test (A6MCT) is an upper limb ergometer assessment used in other neurologic disorders to measure endurance. To study the performance of the A6MCT in the non-ambulatory SMA population, prospective data was collected on 38 individuals with SMA (13 sitters; 25 non-sitters), aged 5 to 74 years (mean = 30.

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Myotonic dystrophy type 1 (DM1) is a genetic neuromuscular progressive multisystem disease that results in a broad spectrum of clinical central nervous system (CNS) involvement, including problems with memory, attention, executive functioning, and social cognition. Fractional anisotropy and mean diffusivity along-tract data calculated using diffusion tensor imaging techniques play a vital role in assessing white matter microstructural changes associated with neurodegeneration caused by DM1. In this work, a novel spectrogram-based deep learning method is proposed to characterize white matter network alterations in DM1 with the goal of building a deep learning model as neuroimaging biomarkers of DM1.

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Tidal marshes store large amounts of organic carbon in their soils. Field data quantifying soil organic carbon (SOC) stocks provide an important resource for researchers, natural resource managers, and policy-makers working towards the protection, restoration, and valuation of these ecosystems. We collated a global dataset of tidal marsh soil organic carbon (MarSOC) from 99 studies that includes location, soil depth, site name, dry bulk density, SOC, and/or soil organic matter (SOM).

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Disease-modifying treatments have transformed the natural history of spinal muscular atrophy (SMA), but the cellular pathways altered by SMN restoration remain undefined and biomarkers cannot yet precisely predict treatment response. We performed an exploratory cerebrospinal fluid (CSF) proteomic study in a diverse sample of SMA patients treated with nusinersen to elucidate therapeutic pathways and identify predictors of motor improvement. Proteomic analyses were performed on CSF samples collected before treatment (T0) and at 6 months (T6) using an Olink panel to quantify 1113 peptides.

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