Publications by authors named "Minshull J"

Objectives: Since June 2022, there has been a rise in the number of ceftriaxone-resistant Neisseria gonorrhoeae cases detected in England (n = 15), of which a third were XDR. We describe the demographic and clinical details of the recent cases and investigate the phenotypic and molecular characteristics of the isolates. For a comprehensive overview, we also reviewed 16 ceftriaxone-resistant cases previously identified in England since December 2015 and performed a global genomic comparison of all publicly available ceftriaxone-resistant N.

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  • The study introduces a method to predict protein expression in tissues using standard H&E stained images, aiming to enhance understanding of diseases like cancer and improve precision medicine outcomes.
  • The authors develop a framework called Ouroboros that generates H&E images from protein profiles and vice versa, highlighting spatial changes in glioblastoma samples.
  • Validation of this method with extensive data shows significant improvements over previous techniques in predicting protein expression and generating virtual images, suggesting potential for better diagnostic and therapeutic decisions.
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  • Depression in older adults is a significant global issue that affects their overall health and increases the risk of mortality, highlighting the need for effective interventions.
  • The study analyzed data from a large cohort of older adults, revealing that depression rates drop until age 80 but then rise again, with a 10% increased mortality risk associated with depression.
  • Findings show correlations between reduced sleep and depression, as well as a decline in synaptic density in the brain linked to depression, emphasizing the importance of early detection and intervention.
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Mammalian cell line stability is an important consideration when establishing a biologics manufacturing process in the biopharmaceutical and diagnostics (IVD) industries. Traditional Chinese hamster ovary (CHO) cell line development methods use a random integration approach that requires transfection, selection, optional amplification, screenings, and single-cell cloning to select clones with acceptable productivity, product quality, and genetic stability. Site-specific integration reduces these disadvantages, and new technologies have been developed to mitigate risks associated with genetic instability.

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  • Corticobasal syndrome is usually linked to common conditions like corticobasal degeneration and Alzheimer's, but this case highlights a rare cause.
  • A 78-year-old woman initially diagnosed with idiopathic Parkinson's disease developed symptoms that led to a revised diagnosis of probable corticobasal syndrome after an MRI showed specific brain atrophy.
  • After her death, post-mortem findings confirmed Pick's disease, demonstrating that it can mimic corticobasal syndrome symptoms, which is important for differential diagnosis.
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  • Myeloid cells are abundant in glioblastoma (GBM) and exist in various forms with different activation states, but there’s limited understanding of how the tumor microenvironment (TME) affects their behavior.
  • Researchers used advanced imaging techniques to analyze and map these myeloid cell populations within the GBM TME, revealing that their distribution is influenced by factors like tissue hypoxia and specific signaling molecules.
  • The study found that the organization of these myeloid cells in certain tumor areas corresponds to patient survival rates, providing important insights into how these cells may impact clinical outcomes in GBM patients.
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  • - The study aimed to explore the relationship between late-life hypertension and Alzheimer's disease (AD) pathology, focusing on individuals over 65 and the effects of antihypertensive medication.
  • - Researchers used self-reported hypertension data and brain assessments from 108 deceased participants, discovering that those with hypertension had lower levels of AD pathology despite no significant cognitive impairment.
  • - The findings imply that late-life hypertension may actually correlate with milder AD pathology, potentially due to factors like reduced blood flow affecting the brain.
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  • FFPE brain tissue in tissue banks is a valuable resource for research, especially with clinical data and psychological testing available.
  • APOE genotyping is crucial for understanding this tissue, but older FFPE samples may not provide reliable results.
  • The study found that DNA from FFPE brain tissue stored for more than three years may degrade, affecting APOE genotyping effectiveness.
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Aims: Sixty-four million pharmacy-filled multicompartment medication compliance aids (MCAs) are dispensed by pharmacies in England each year. Despite the widespread use of MCAs and evidence that their use may be associated with harm there is no national consensus regarding MCA provision by acute hospital Trusts in England. The aim was to determine current practice for initiation and supply of MCAs in acute hospital Trusts in England and the potential consequences for patients and hospitals.

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  • Early diagnosis of Alzheimer's disease (AD) through cognitive testing can lead to early intervention, and the Telephone Assessment for Cognitive Screening (TICS) is effective in screening for cognitive impairment, though its ability to signal future AD risk is still being explored.
  • The study investigates the relationship between TICS scores collected over 13 years and the cognitive status of participants at death, alongside their neuropathological indices of AD.
  • Results show that lower TICS scores correlate with cognitive impairment and AD pathology in participants, suggesting that TICS could be a useful tool for identifying those at risk of developing AD long before symptoms appear, potentially allowing for early intervention strategies.
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Objectives: A Finnish (CT) new variant was detected in 2019 that escaped detection in the Hologic Aptima Combo 2 (AC2) assay due to a C1515T mutation in the CT 23S rRNA target region. Reflex testing of CT-negative/CT-equivocal specimens as well as those positive for (NG) with the Hologic Aptima CT (ACT) assay was recommended to identify any CT variants.

Methods: From June to October 2019, specimens with discrepant AC2/ACT CT results were submitted to Public Health England and screened for detectable CT DNA using an inhouse real-time (RT)-PCR.

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Introduction: The concept of person-centred care is regarded as an essential approach to healthcare. A core component of person-centred care is the shared decision-making process. There is evidence that effective shared decision-making can improve people's satisfaction with their care.

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The development of highly productive, genetically stable manufacturing cell lines is on the critical path to IND filing for protein-based biologic drugs. Here, we describe the Leap-In Transposase® platform, a novel transposon-based mammalian (e.g.

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  • The term "Primary age-related tauopathy" (PART) refers to a condition characterized by the presence of neurofibrillary tangles without associated beta-amyloid pathology, affecting both cognitively normal and impaired individuals.
  • Research indicates that the genetic factor Apolipoprotein E (APOE) ε4 is less common in PART compared to Alzheimer's disease (AD), with APOE ε2 being more prevalent in cases of PART.
  • Findings suggest that individuals with definite PART tend to experience less cognitive impairment than those diagnosed with AD, potentially due to the differing effects of APOE genotypes on Aβ pathology and cognition in older adults.
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  • - The study investigates the link between early depression symptoms and the risk of developing Alzheimer's disease (AD), focusing on how mood changes might indicate a higher likelihood of cognitive impairment later in life.
  • - Researchers analyzed data from a long-term study involving assessments on depression and cognitive status, revealing that higher depression scores were associated with greater cognitive impairment and AD pathology at death.
  • - Findings suggest that early depression symptoms could serve as a potential early diagnostic marker for Alzheimer's by indicating underlying neurological changes related to the disease, even occurring decades before death.
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  • A study explored the connection between genotype and lifespan using data from cognitive health research.
  • The research found that individuals with the 4 allele had a lower chance of reaching 80+ years while remaining cognitively healthy, while 2 allele carriers generally lived longer and stayed cognitively normal.
  • These findings suggest that genotype does impact longevity, particularly in those who are cognitively impaired.
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  • FXTAS is a neurodegenerative disorder triggered by an expansion of CGG repeats in the FMR1 gene, leading to symptoms like cognitive decline, tremors, and gait issues.
  • A study reports neuropathological findings in a case who experienced cognitive impairment without tremor, confirming the presence of p62-positive inclusions and other cellular changes across various brain regions.
  • Results indicate that factors such as age and disease duration can influence the severity of FXTAS pathology, and suggest using p62 staining as a diagnostic tool for atypical cases.
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Background: The pathological features of Alzheimer's disease (AD) are well described but little is known as to how both neurodegeneration and vascular changes might interact in causing cognitive impairment.

Objective: The present study aims to investigate relationships between vascular and AD pathology in cognitively healthy and cognitively impaired individuals with a particular emphasis on those at intermediate Braak tau stages.

Methods: We investigated the interplay between Braak tau stage and measures of vascular pathology as described by the vascular cognitive impairment neuropathology guidelines (VCING) in 185 brains from the Brains for Dementia Research programme and The University of Manchester Longitudinal Study of Cognition in Healthy Old Age.

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In the present study, we have characterized and compared individuals whose brains were donated as part of The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age (UoM) with those donated through the Manchester arm of the UK Brains for Dementia Research (BDR) program. The aim of this study was to investigate how differences in study recruitment may affect final pathological composition of cohort studies. The UoM cohort was established as a longitudinal study of aging and cognition whereas the BDR program was established, prima facie, to collect brains from both demented and non-demented individuals for the purpose of building a tissue research resource.

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Deprescribing is complex and multifactorial with multiple approaches described in the literature. Internationally, there are guidelines and tools available to aid clinicians and patients to identify and safely withdraw inappropriate medications, post a shared decision-making medicines optimisation review. The increase in available treatments and use of single disease model guidelines have led to a healthcare system geared towards prescribing, with deprescribing often seen as a separate activity.

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Clonally derived cell lines (CDCL) from Chinese Hamster Ovary (CHO) host cell lines, remain the most popular method to manufacture therapeutic proteins. However, CHO cell pools are increasingly being used as an alternate method to produce therapeutic proteins for preclinical drug development in an effort to shorten the time required for new drug development. It is essential that these CHO pools exhibit the desired attributes of CHO CDCLs such as high protein titers and consistent product quality attributes (PQAs).

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