Publications by authors named "Myles J"

Article Synopsis
  • - Digital breast tomosynthesis (DBT), when used with a synthetic 2D mammogram (S2D), exposes women to higher radiation but may enhance cancer detection compared to full-field digital mammography (FFDM) alone.
  • - A review of 17 studies, including 13 for meta-analysis, found that DBT plus S2D provided a higher cancer detection rate compared to FFDM alone, while also showing similar accuracy to DBT with FFDM.
  • - The findings suggest that integrating S2D with DBT in breast cancer screening is effective and maintains the safety and performance of the imaging process.
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Basophils are the rarest circulating white blood cells (WBCs), but they play important roles in allergic disorders and other diseases. To enhance diagnostic capabilities, it would be desirable to isolate and analyze basophils efficiently from small blood samples. In 100 μL of whole blood, there are typically ~10 basophils, outnumbered by ~10 WBCs and ~10 red blood cells (RBCs).

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  • Pathologic re-review of TURBT specimens at a tertiary care center was evaluated to understand its impact on disease risk stratification for bladder cancer patients.
  • Out of 173 patients whose specimens were re-reviewed, changes in grade, clinical stage, and risk stratification were observed, particularly in those with less advanced (
  • The study found that re-review by a GU pathologist affected more than 20% of patients' risk assessments, highlighting its importance in potentially altering patient management strategies.
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  • GM1 gangliosidosis (GM1) is a lysosomal disorder caused by mutations in the GLB1 gene, leading to serious neurodegeneration and currently has no approved treatments.
  • A study involving 41 patients with type II GM1 revealed distinct genetic variants and observed that many children had normal hearing and did not exhibit typical symptoms seen in type I GM1.
  • The research highlighted progressive brain atrophy and identified crucial correlations between brain chemistry changes and patient behavior scores, emphasizing the importance of this long-term study for improving diagnosis and developing future therapies.
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  • GM1 gangliosidosis is a rare genetic disease mainly affecting children, characterized by neurodegeneration, and currently has no approved treatments but is under investigation through gene therapy and other trials.
  • A study involving 41 individuals with type II GM1 assessed various health factors, revealing unique characteristics and differences compared to type I infantile forms, such as normal hearing and specific heart issues in older children.
  • The study provided new insights into the disease's progression and aimed to correct misunderstandings about type II GM1, enhancing the knowledge base for future diagnosis and treatment approaches.
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Purpose: To determine the significance to patients of changes in health-related quality-of-life (HLQ) scores assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30).

Patients And Methods: A subjective significance questionnaire (SSQ), which asks patients about perceived changes in physical, emotional, and social functioning and in global quality of life (global QL) and the QLQ-C30 were completed by patients who received chemotherapy for either breast cancer or small-cell lung cancer (SCLC). In the SSQ, patients rated their perception of change since the last time they completed the QLQ-C30 using a 7-category scale that ranged from "much worse" through "no change" to "much better.

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Purpose: Immune checkpoint inhibition (ICI) therapy represents one of the great advances in the field of oncology, highlighted by the Nobel Prize in 2018. Multiple predictive biomarkers for ICI benefit have been proposed. These include assessment of programmed death ligand-1 expression by immunohistochemistry, and determination of mutational genotype (microsatellite instability or mismatch repair deficiency or tumor mutational burden) as a reflection of neoantigen expression.

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As SARS-CoV-2 infections continue to cause hospital admissions around the world, there is a continued need to accurately assess those at highest risk of death to guide resource use and clinical management. The ISARIC 4C mortality score provides mortality risk prediction at admission to hospital based on demographic and physiological parameters. Here we evaluate dynamic use of the 4C score at different points following admission.

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Article Synopsis
  • Breast screening services in England were paused during the COVID-19 pandemic, which has led to concerns about delayed detection of breast cancers and potential increases in cancer deaths.
  • Approximately 1.5 million women experienced delays of 2-7 months in their screenings, potentially resulting in 2,500 to 4,100 cancers shifting from screen-detected to symptomatic status, and leading to an estimated 148 to 452 additional deaths from these cancers.
  • Overall, the study projects that there could be 148 to 687 extra breast cancer deaths due to the disruptions caused by the pandemic, largely dependent on how quickly screening services can resume and address the backlog.
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Renal cell carcinoma (RCC) in the kidney allograft is a relatively rare complication most commonly seen approximately a decade or more after transplant. We report a case of diffuse multifocal RCC within 6 months of transplant. The initial signal leading to an abnormality in the graft was an elevated routine cell-free DNA.

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Papillary renal cell carcinoma (PRCC) is well-recognized as a morphologically and molecularly heterogenous group of kidney tumors with variable clinical behavior. Our goal was to analyze a unique histologic pattern of PRCC we have observed in routine practice to evaluate for potential clinical significance or distinct molecular signature. We identified 42 cases of PRCC showing a morphologically distinct architecture characterized by numerous epithelial-lined cysts containing the papillary tumor (herein called "microcysts"), which are typically separated by fibrous stroma.

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Background: Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience.

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  • Amyotrophic lateral sclerosis (ALS) leads to progressive death of motor neurons, typically resulting in death within 5 years of diagnosis, and the role of C-boutons in disease progression was investigated.
  • Research found that while silencing C-boutons did not change humane endpoints in mice, it significantly improved muscle innervation and behavioral capabilities when combined with swimming exercises.
  • The findings suggest that altering C-bouton activity alongside targeted training could potentially enhance mobility and quality of life for ALS patients.
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Background: This study investigates whether quantitative breast density (BD) serves as an imaging biomarker for more intensive breast cancer screening by predicting interval, and node-positive cancers.

Methods: This case-control study of 1204 women aged 47-73 includes 599 cancer cases (302 screen-detected, 297 interval; 239 node-positive, 360 node-negative) and 605 controls. Automated BD software calculated fibroglandular volume (FGV), volumetric breast density (VBD) and density grade (DG).

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Background: After adoption, children exposed to institutionalized care show significant improvement, but incomplete recovery of growth and developmental milestones. There is a paucity of data regarding risk and protective factors in children adopted from institutionalized care. This prospective study followed children recently adopted from institutionalized care to investigate the relationship between family environment, executive function, and behavioral outcomes.

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Purpose: To conduct a proof-of-principle study to identify subtypes of propionic acidemia (PA) and associated biomarkers.

Methods: Data from a clinically diverse PA patient population ( https://clinicaltrials.gov/ct2/show/NCT02890342 ) were used to train and test machine learning models, identify PA-relevant biomarkers, and perform validation analysis using data from liver-transplanted participants.

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We present the first joint analysis of cluster abundances and auto or cross-correlations of three cosmic tracer fields: galaxy density, weak gravitational lensing shear, and cluster density split by optical richness. From a joint analysis (4×2pt+N) of cluster abundances, three cluster cross-correlations, and the auto correlations of the galaxy density measured from the first year data of the Dark Energy Survey, we obtain Ω_{m}=0.305_{-0.

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Context.—: Next-generation sequencing is a powerful clinical tool for cancer management but can produce incidental/secondary findings that require special consideration.

Objective.

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Objectives: To evaluate the effect of general practitioner endorsement accompanying the screening kit rather than with the invitation letter on participation in the NHS Bowel Cancer Screening Programme and on the socioeconomic gradient in participation in the Programme.

Methods: The NHS Bowel Cancer Screening Programme in England is delivered via five regional hubs. In early 2016, we carried out a cluster-randomised trial, with hub-day of invitation as the randomisation unit.

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Background: There remains disagreement on the long-term effect of mammographic screening in women aged 40-49 years.

Objectives: The long-term follow-up of a randomised controlled trial that offered annual mammography to women aged 40-49 years. The estimation of the effect of these mammograms on breast cancer and other-cause mortality, and the effect on incidence, with implications for overdiagnosis.

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Background: The appropriate age range for breast cancer screening remains a matter of debate. We aimed to estimate the effect of mammographic screening at ages 40-48 years on breast cancer mortality.

Methods: We did a randomised, controlled trial involving 23 breast screening units across Great Britain.

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Article Synopsis
  • The study investigates the differences between cause-specific and relative survival estimates in common cancers.
  • Findings reveal that relative survival is generally lower than cause-specific survival for most cancers except breast and prostate, with specific corrections made for misclassified causes of death and other factors like ischaemic heart disease and smoking.
  • The conclusion suggests relative survival is often more reliable, though adjustments may be needed for accuracy in certain cancers like lung and prostate, advocating for improved demographic inclusion in survival calculations.
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Purpose: Propionic acidemia (PA) is a severe metabolic disorder characterized by multiorgan pathology, including renal disease. The prevalence of chronic kidney disease (CKD) in PA patients and factors associated with CKD in PA are not known.

Methods: Thirty-one subjects diagnosed with PA underwent laboratory and clinical evaluations through a dedicated natural history study at the National Institutes of Health (ClinicalTrials.

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Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by progressive motor neuron (MN) death that leads to muscle weakness, paralysis, and eventually death. When symptoms become clinically evident, patients and ALS model animals (mSod1 mice) have already lost a large portion of motor units, suggesting the existence of a compensatory mechanism that allows for reactively normal movement despite denervation. Furthermore, it has been shown that specialized cholinergic synapses, the C-boutons, regulate activity strength of motor output in a task dependent manner.

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