Optimization of the supercritical fluidized bed process for sirolimus coating and drug release.

Directly coating an active pharmaceutical ingredient (API) onto excipient granules has been a common approach to prepare solid dosage forms. The combination of supercritical anti-solvent (SAS) and fluidized bed (FB) coating technology (SAS-FB) has the advantages of preventing nanoparticles aggregation, oxidation and light exposure. However individual operating parameters and factors which contribute to the overall coating efficiency remain to be defined.

Data extraction for epidemiological research (DExtER): a novel tool for automated clinical epidemiology studies.

The use of primary care electronic health records for research is abundant. The benefits gained from utilising such records lies in their size, longitudinal data collection and data quality. However, the use of such data to undertake high quality epidemiological studies, can lead to significant challenges particularly in dealing with misclassification, variation in coding and the significant effort required to pre-process the data in a meaningful format for statistical analysis.

Pulmonary Artery Thrombosis: A Diagnosis That Strives for Its Independence.

According to a widespread theory, thrombotic masses are not formed in the pulmonary artery (PA) but result from migration of blood clots from the venous system. This concept has prevailed in clinical practice for more than a century. However, a new technologic era has brought forth more diagnostic possibilities, and it has been shown that thrombotic masses in the PA could, in many cases, be found without any obvious source of emboli.

The association between exposure to childhood maltreatment and the subsequent development of functional somatic and visceral pain syndromes.

Background: Childhood maltreatment is a global public health issue linked to a vast mortality and morbidity burden. This study builds on current literature to explore the risk of developing central sensitivity syndromes (CSS) (consisting of somatic and visceral pain syndromes) subsequent to childhood maltreatment exposure.

Methods: A retrospective population based open cohort study using the UK primary care database, 'The Health Improvement Network,' between 1st January 1995-31st December 2018.

Classifying individuals with and without patellofemoral pain syndrome using ground force profiles - Development of a method using functional data boosting.

Background: Predictors of recovery in patellofemoral pain syndrome (PFPS) currently used in prognostic models are scalar in nature, despite many physiological measures originally lying on the functional scale. Traditional modelling techniques cannot harness the potential predictive value of functional physiological variables.

Research Question: What is the classification performance of PFPS status of a statistical model when using functional ground reaction force (GRF) time-series?

Methods: Thirty-one individuals (control = 17, PFPS = 14) performed maximal countermovement jumps, on two force plates.

Individuals with patellofemoral pain syndrome have altered inter-leg force coordination.

Background: Patellofemoral pain syndrome (PFPS) is one of the most common musculoskeletal disorders. Pain may be further exacerbated by atypical motor coordination strategies. It has been thought that low coordination variability may concentrate loads onto painful knee tissues.

Zeta-Potential Read-Across Model Utilizing Nanodescriptors Extracted via the NanoXtract Image Analysis Tool Available on the Enalos Nanoinformatics Cloud Platform.

Zeta potential is one of the most critical properties of nanomaterials (NMs) which provides an estimation of the surface charge, and therefore electrostatic stability in medium and, in practical terms, influences the NM's tendency to form agglomerates and to interact with cellular membranes. This paper describes a robust and accurate read-across model to predict NM zeta potential utilizing as the input data a set of image descriptors derived from transmission electron microscopy (TEM) images of the NMs. The image descriptors are calculated using NanoXtract (http://enaloscloud.

Investigation of Inactive-State κ Opioid Receptor Homodimerization via Single-Molecule Microscopy Using New Antagonistic Fluorescent Probes.

Opioid receptors (ORs) are among the best-studied G protein-coupled receptors due to their involvement in neurological disorders and important role in pain treatment. Contrary to the classical monomeric model, indirect evidence suggests that ORs might form dimers, which could be endowed with a distinct pharmacological profile, and, thus, be targeted to develop innovative pharmacological therapies. However, direct evidence for the spontaneous formation of OR dimers in living cells under physiological conditions is missing.

Interpretable machine learning models for classifying low back pain status using functional physiological variables.

Purpose: To evaluate the predictive performance of statistical models which distinguishes different low back pain (LBP) sub-types and healthy controls, using as input predictors the time-varying signals of electromyographic and kinematic variables, collected during low-load lifting.

Methods: Motion capture with electromyography (EMG) assessment was performed on 49 participants [healthy control (con) = 16, remission LBP (rmLBP) = 16, current LBP (LBP) = 17], whilst performing a low-load lifting task, to extract a total of 40 predictors (kinematic and electromyographic variables). Three statistical models were developed using functional data boosting (FDboost), for binary classification of LBP statuses (model 1: con vs.

Effects of Germline CYP2W1*6 and CYP2B6*6 Single Nucleotide Polymorphisms on Mitotane Treatment in Adrenocortical Carcinoma: A Multicenter ENSAT Study.

Mitotane is the only approved drug for advanced adrenocortical carcinoma (ACC) and no biomarkers are available to predict attainment of therapeutic plasma concentrations and clinical response. Aim of the study was to evaluate the suitability of cytochrome P450(CYP)2W1 and CYP2B6 single nucleotide polymorphisms (SNPs) as biomarkers. A multicenter cohort study including 182 ACC patients (F/M = 121/61) treated with mitotane monotherapy after radical resection (group A, = 103) or in not completely resectable, recurrent or advanced disease (group B, = 79) was performed.

The Self-Sealing Capacity of Environmentally Friendly, Highly Damped, Fibre-Reinforced Concrete.

Cracks could attenuate the service life of concrete structures because of the intrusion of hazardous substances such as water. In this study, different proportions of Duras S500 fibre were employed to investigate the self-sealing capacity of environmentally friendly, highly damped, fibre-reinforced concrete (EFHDFRC) containing 5% crumb rubber. The workability of EFHDFRC with different proportions of the fibre was investigated by mechanical properties test.

Epigenetic regulation of human papillomavirus transcription in the productive virus life cycle.

Human papillomaviruses (HPV) are a large family of viruses which contain a circular, double-stranded DNA genome of approximately 8000 base pairs. The viral DNA is chromatinized by the recruitment of cellular histones which are subject to host cell-mediated post-translational epigenetic modification recognized as an important mechanism of virus transcription regulation. The HPV life cycle is dependent on the terminal differentiation of the target cell within epithelia-the keratinocyte.

Classifying neck pain status using scalar and functional biomechanical variables - development of a method using functional data boosting.

Background: Individuals with neck pain have different movement and muscular activation (collectively termed as biomechanical variables) patterns compared to healthy individuals. Incorporating biomechanical variables as covariates into prognostic models is challenging due to the high dimensionality of the data.

Research Question: What is the classification performance of neck pain status of a statistical model which uses both scalar and functional biomechanical covariates?

Methods: Motion capture with electromyography assessment on the sternocleidomastoid, splenius cervicis, erector spinae, was performed on 21 healthy and 26 individuals with neck pain during walking over three gait conditions (rectilinear, curvilinear clockwise (CW) and counterclockwise (CCW)).

Selective and Wash-Resistant Fluorescent Dihydrocodeinone Derivatives Allow Single-Molecule Imaging of μ-Opioid Receptor Dimerization.

μ-Opioid receptors (μ-ORs) play a critical role in the modulation of pain and mediate the effects of the most powerful analgesic drugs. Despite extensive efforts, it remains insufficiently understood how μ-ORs produce specific effects in living cells. We developed new fluorescent ligands based on the μ-OR antagonist E-p-nitrocinnamoylamino-dihydrocodeinone (CACO), that display high affinity, long residence time and pronounced selectivity.

RUNX1-ETO Depletion in t(8;21) AML Leads to C/EBPα- and AP-1-Mediated Alterations in Enhancer-Promoter Interaction.

Acute myeloid leukemia (AML) is associated with mutations in transcriptional and epigenetic regulator genes impairing myeloid differentiation. The t(8;21)(q22;q22) translocation generates the RUNX1-ETO fusion protein, which interferes with the hematopoietic master regulator RUNX1. We previously showed that the maintenance of t(8;21) AML is dependent on RUNX1-ETO expression.

Conscious perception of natural images is constrained by category-related visual features.

Conscious perception is crucial for adaptive behaviour yet access to consciousness varies for different types of objects. The visual system comprises regions with widely distributed category information and exemplar-level representations that cluster according to category. Does this categorical organisation in the brain provide insight into object-specific access to consciousness? We address this question using the Attentional Blink approach with visual objects as targets.

Women's perspectives on caesarean section recovery, infection and the PREPS trial: a qualitative pilot study.

Background: In England, 27.8% of all pregnant women undergo caesarean sections (CS) to deliver their babies. Women undergoing CS are at risk of developing sepsis and post-natal infections, which not only contribute significantly to maternal mortality and morbidity, but also negatively impact upon post-natal recovery and wellbeing.

Interventions to Increase the Rate of Influenza and Pneumococcal Vaccination in Patients with Chronic Obstructive Pulmonary Disease: A Scoping Review.

Current evidence suggests that patients with chronic obstructive pulmonary disease (COPD) should receive influenza and pneumococcal vaccinations. Despite international guidelines recommending vaccination in patients with COPD, many patients remain unvaccinated. Reasons for vaccine non-acceptance are multifaceted and are likely to be influenced by multiple psychosocial factors and pre-existing health beliefs.

An acute exposure to intermittent negative airway pressure elicits respiratory long-term facilitation in awake humans.

Background: A sustained elevation in respiratory drive following removal of the inducing stimulus is known as respiratory long-term facilitation (rLTF). We investigated whether an acute exposure to intermittent negative airway pressure (INAP) elicits rLTF in humans.

Method: 13 healthy males (20.

Clinical implications of heterogeneity in PD-L1 immunohistochemical detection in hepatocellular carcinoma: the Blueprint-HCC study.

Programmed cell death ligand-1 immunohistochemical detection (PD-L1 IHC) is a putative predictor of response to PD-1/PD-L1-targeted checkpoint inhibitors. However, there is no gold standard assay in hepatocellular carcinoma (HCC). We evaluated 5 PD-L1 IHC assay platforms (E1LN3, 28-8, 22c3, SP263 and SP142) in 100 HCCs reporting PD-L1 expression in malignant (M) and tumour-infiltrating immune cells (TICs) and non-tumorous cirrhotic tissues (NTICs).

Intimate partner violence and temporomandibular joint disorder.

Objective: To assess the relationship between Intimate partner violence (IPV) (a highly prevalent form of domestic abuse) with the subsequent development of temporomandibular joint disorder (TMD).

Methods: A retrospective open cohort study using a UK primary care database was undertaken. 18,547 women exposed to IPV were matched by age to 74,188 unexposed women.

Global long terminal repeat activation participates in establishing the unique gene expression programme of classical Hodgkin lymphoma.

Long terminal repeat (LTR) elements are wide-spread in the human genome and have the potential to act as promoters and enhancers. Their expression is therefore under tight epigenetic control. We previously reported in classical Hodgkin Lymphoma (cHL) that a member of the THE1B class of LTR elements acted as a promoter for the proto-oncogene and growth factor receptor gene CSF1R and that expression of this gene is required for cHL tumour survival.

Ward-Based Non-Invasive Ventilation in Acute Exacerbations of COPD: A Narrative Review of Current Practice and Outcomes in the UK.

Non-invasive ventilation (NIV) is frequently used as a treatment for acute hypercapnic respiratory failure (AHRF) in hospitalised patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). In the UK, many patients with AHRF secondary to AECOPD are treated with ward-based NIV, rather than being treated in critical care. NIV has been increasingly used as an alternative to invasive ventilation and as a ceiling of treatment in patients with a 'do not intubate' order.

The Role of Occupational and Environmental Exposures in the Pathogenesis of Idiopathic Pulmonary Fibrosis: A Narrative Literature Review.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterised by a progressive and irreversible decline in lung function, which is associated with poor long-term survival. The pathogenesis of IPF is incompletely understood. An accumulating body of evidence, obtained over the past three decades, suggests that occupational and environmental exposures may play a role in the development of IPF.