Publications by authors named "Mullen P"

We investigated the characteristics of high-quality health and social care for people on probation and how they might be measured. Online open-ended survey responses and focus group data were analysed using thematic analysis. Providing high-quality care involves an understanding of the population's needs; tailoring practice to accommodate and meet individuals' needs; inter-agency collaboration; and seeking and acting on lived experience input.

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The combination of gemcitabine with platinum agents is a widely used chemotherapy regimen for a number of tumour types. Gemcitabine plus cisplatin remains the current therapeutic choice for biliary tract cancer. Gemcitabine is associated with multiple cellular drug resistance mechanisms and other limitations and has thereforelined in use.

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We report that diazepam binding inhibitor (DBI) is a glial messenger mediating crosstalk between satellite glial cells (SGCs) and sensory neurons in the dorsal root ganglion (DRG). DBI is highly expressed in SGCs of mice, rats, and humans, but not in sensory neurons or most other DRG-resident cells. Knockdown of DBI results in a robust mechanical hypersensitivity without major effects on other sensory modalities.

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The capacity to deal with stress declines during the aging process, and preservation of cellular stress responses is critical to healthy aging. The unfolded protein response of the endoplasmic reticulum (UPR) is one such conserved mechanism, which is critical for the maintenance of several major functions of the ER during stress, including protein folding and lipid metabolism. Hyperactivation of the UPR by overexpression of the major transcription factor, , solely in neurons drives lifespan extension as neurons send a neurotransmitter-based signal to other tissue to activate UPR in a non-autonomous fashion.

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Humans are living longer, but this is accompanied by an increased incidence of age-related chronic diseases. Many of these diseases are influenced by age-associated metabolic dysregulation, but how metabolism changes in multiple organs during aging in males and females is not known. Answering this could reveal new mechanisms of aging and age-targeted therapeutics.

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Background: The origin of novel SARS-CoV-2 spike sequences found in wastewater, without corresponding detection in clinical specimens, remains unclear. We sought to determine the origin of one such cryptic wastewater lineage by tracking and characterising its persistence and genomic evolution over time.

Methods: We first detected a cryptic lineage, WI-CL-001, in municipal wastewater in Wisconsin, USA, in January, 2022.

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We report that diazepam binding inhibitor (DBI) is a glial messenger mediating satellite glia-sensory neuron crosstalk in the dorsal root ganglion (DRG). DBI is highly and specifically expressed in satellite glia cells (SGCs) of mice, rat and human, but not in sensory neurons or other DRG-resident cells. Knockdown of DBI results in a robust mechanical hypersensitivity without significant effects on other sensory modalities.

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Despite the higher incidence of cancer with increasing age, few preclinical or clinical studies incorporate age. This, coupled with an aging world population, requires that we improve our understanding of how aging affects cancer development, progression, and treatment. One key area will be how the tumor microenvironment (TME) changes with age.

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Introduction: Fluoropyrimidines, principally 5-fluorouracil (5-FU), remain a key component of chemotherapy regimens for multiple cancer types, in particular colorectal and other gastrointestinal malignancies. To overcome key limitations and pharmacologic challenges that hinder the clinical utility of 5-FU, NUC-3373, a phosphoramidate transformation of 5-fluorodeoxyuridine, was designed to improve the efficacy and safety profile as well as the administration challenges associated with 5-FU.

Methods: Human colorectal cancer cell lines HCT116 and SW480 were treated with sub-IC doses of NUC-3373 or 5-FU.

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Accumulating observations suggest that peripheral somatosensory ganglia may regulate nociceptive transmission, yet direct evidence is sparse. Here, in experiments on rats and mice, we show that the peripheral afferent nociceptive information undergoes dynamic filtering within the dorsal root ganglion (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using synchronous in vivo electrophysiological recordings from the peripheral and central processes of sensory neurons (in the spinal nerve and dorsal root), ganglionic transplantation of GABAergic progenitor cells, and optogenetics, we demonstrate existence of tonic and dynamic filtering of action potentials traveling through the DRG.

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The pancreatic tumor microenvironment drives deregulated nutrient availability. Accordingly, pancreatic cancer cells require metabolic adaptations to survive and proliferate. Pancreatic cancer subtypes have been characterized by transcriptional and functional differences, with subtypes reported to exist within the same tumor.

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The classification of biological neuron types and networks poses challenges to the full understanding of the human brain's organisation and functioning. In this paper, we develop a novel objective classification model of biological neuronal morphology and electrical types and their networks, based on the attributes of neuronal communication using supervised machine learning solutions. This presents advantages compared to the existing approaches in neuroinformatics since the data related to mutual information or delay between neurons obtained from spike trains are more abundant than conventional morphological data.

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EBV gene expression is repressed during viral latency to prevent an immune response, but it is not known how metabolism contributes to this silencing. In this issue of Cell Metabolism, Guo et al. describe how methionine restriction reactivates the expression of EBV genes, offering new therapeutic approaches against EBV-driven diseases.

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Background: Despite the development of numerous evidence-based interventions (EBIs), many go unused in practice. Hesitations to use existing EBIs may be due to a lack of understanding about EBI components and what it would take to adapt it or implement it as designed. To improve the use of EBIs, program planners need to understand their goals, core components, and mechanisms of action.

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Meta-analysis (MA) quantitatively summarizes the findings of independent studies and is considered the highest quality of evidence for evidence-based medicine. However, issues in reporting and methodological rigor of MA hamper reproducibility and create the potential for bias. By applying PRISMA reporting guideline and AMSTAR2 execution guidelines on 40 cervical cancer MA samples covering topics such as interventions and risk factors, we determined the extent to which MA execution adhered to best practice guidelines.

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Nitrovin (NTV) belongs to a class of antibiotics called nitrofurans, which are classified as nonallowed pharmacologically active substances that do not have a maximum residue limit listed in EU legislation. The objectives of this study were to confirm aminoguanidine (AGN) as a suitable marker residue to monitor NTV abuse and to investigate its persistence in porcine tissues. In this work, pigs were fed with NTV-medicated feed (50 mg/kg), and tissues (kidney, muscle, and liver) and plasma were collected on different withdrawal days.

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Probation staff perform a health-related role involving identifying health-related drivers of offending behaviour; facilitating access to support for these, including continuity of care for people leaving prison; and advising the courts on appropriate sentencing. This study analyses data from probation staff surveys and interviews with people that were under probation supervision during the pandemic to investigate the impact of the response to the pandemic on a) this health-related role, b) the lived experience of accessing health support whilst engaging with probation, and c) partnership working and pathways into healthcare for people under probation supervision.

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Aim: A model of progressively endocrine-resistant breast cancer was investigated to identify changes that can occur in signaling pathways after endocrine manipulation.

Methods: The MCF7 breast cancer model is sensitive to estrogens and anti-estrogens while variant lines previously derived from wild-type MCF7 are either relatively 17β-estradiol (E)-insensitive (LCC1) or fully resistant to estrogen and anti-estrogens (LCC9).

Results: In LCC1 and LCC9 cell lines, loss of estrogen sensitivity was accompanied by loss of growth response to transforming growth factor alpha (TGFα), heregulin-beta and pertuzumab.

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Autonomic parasympathetic preganglionic neurons (PGNs) drive contraction of the bladder during micturition but remain quiescent during bladder filling. This quiescence is postulated to be because of recurrent inhibition of PGN by fast-firing adjoining interneurons. Here, we defined four distinct neuronal types within Lamina VII, where PGN are situated, by combining whole cell patch clamp recordings with k-means clustering of a range of electrophysiological parameters.

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Respiratory failure secondary to rib fractures is a major source of morbidity and mortality in trauma patients, particularly in older populations. Management of pain in these patients is complex due to the nature of the injuries. We present 3 patients who underwent a video-assisted thoracoscopic cryoablation of intercostal nerves for pain control after chest trauma.

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In the present study, we examined the ability of Self-Determination Theory's causality orientations to predict alcohol use and abstinence self-efficacy. We also provided suggestions for counselors supporting client and student autonomy in clinical practice. This study sought to answer the following questions: (a) Does a person's causality orientation (autonomy, control, and impersonal) predict their alcohol use? (2) Does a person's causality orientation (autonomy, control, and impersonal) predict their temptation to use drugs and alcohol? (3) Does a person's causality orientation (autonomy, control, and impersonal) predict their confidence to use drugs and alcohol? We utilized Amazon's Mechanical Turk (MTurk), a crowdsourced online labor market approach to collect data from a community sample.

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Implementation of evidence-based interventions (EBIs) can help to increase colorectal cancer screening (CRCS). Potential users of CRCS EBIs are often unclear about the specific features, logic, and core elements of existing EBIs, making it challenging to use or adapt them. We used EBI Mapping, a systematic process developed from Intervention Mapping that identifies an EBI's components and logic, to characterize existing CRCS EBIs from the National Cancer Institute's Evidence-Based Cancer Control Programs website.

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Background: Patient and public involvement is increasingly considered important in health research. This paper reflects, from both academic and lived experience perspectives, on involving people with lived experience in a study exploring cancer care in prison and how by doing this it enriched the research process.

Methods: This paper is based on written and verbal reflections of the lived experience researchers and academic researchers involved in a study exploring the diagnosis and treatment of people with cancer in prison.

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