A general and accessible approach to enrichment and characterisation of natural anti-Neu5Gc antibodies from human samples.

-Glycolylneuraminic acid (Neu5Gc) is a non-human sialic acid which is presented on the surface of human cells following uptake from dietary sources. Antibodies against Neu5Gc have implications for many aspects of human health such as inflammation, xenograft rejection and cancer. However, current methods to detect and study anti-Neu5Gc antibodies require complex synthesis of glycan structures, animal handling expertise, or access to expensive reagents and equipment.

A qualitative exploration of service users' experiences of weight management conversations in a mental health setting.

Objective: Healthcare professionals often use opportunistic weight management conversations, aligned with the Making Every Contact Count (MECC) approach, to provide motivational support to service users. While research supports this practice from the professionals' perspective, the views of service users on these interactions remain understudied. The aim of this study was to explore the experiences of service users with serious mental illness regarding weight management conversations with healthcare professionals.

Assessing fidelity of design and training of Making Every Contact Count (MECC) in a mental health inpatient setting.

Background: Making Every Contact Count (MECC) is a public health strategy which strives to enable brief interventions to be implemented through opportunistic healthy lifestyle conversations. In a mental health inpatient setting a bespoke MECC training package has been developed to encourage cascade training through a train the trainer model and to incorporate an additional regional health strategy A Weight Off Your Mind into Core MECC training to provide a focus on healthy weight management. This study evaluated the fidelity of design of MECC in the mental health inpatient setting and fidelity of the training package currently being cascaded across the region.

A systematic review reveals conflicting evidence for the prevalence of antibodies against the sialic acid 'xenoautoantigen' Neu5Gc in humans and the need for a standardised approach to quantification.

Despite an array of hypothesised implications for health, disease, and therapeutic development, antibodies against the non-human sialic acid -glycolylneuraminic acid (Neu5Gc) remain a subject of much debate. This systematic review of 114 publications aimed to generate a comprehensive overview of published studies in this field, addressing both the reported prevalence of anti-Neu5Gc antibodies in the human population and whether experimental variation accounts for the conflicting reports about the extent of this response. Absolute titres of anti-Neu5Gc antibodies, the reported prevalence of these antibodies, and the individual variation observed within experiments were analysed and grouped according to biological context ('inflammation', 'xenotransplantation', 'biotherapeutic use', 'cancer', and 'healthy populations'), detection method, target epitope selection, and choice of blocking agent.

ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer.

Immune checkpoint blockade has yet to produce robust anti-cancer responses for prostate cancer. Sialyltransferases have been shown across several solid tumours, including breast, melanoma, colorectal and prostate to promote immune suppression by synthesising sialoglycans, which act as ligands for Siglec receptors. We report that ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) levels negatively correlate with androgen signalling in prostate tumours.

CDC20 Is Regulated by the Histone Methyltransferase, KMT5A, in Castration-Resistant Prostate Cancer.

The methyltransferase KMT5A has been proposed as an oncogene in prostate cancer and therefore represents a putative therapeutic target. To confirm this hypothesis, we have performed a microarray study on a prostate cancer cell line model of androgen independence following KMT5A knockdown in the presence of the transcriptionally active androgen receptor (AR) to understand which genes and cellular processes are regulated by KMT5A in the presence of an active AR. We observed that 301 genes were down-regulated whilst 408 were up-regulated when KMT5A expression was reduced.

Engineering prostate cancer in vitro: what does it take?

A key challenge in the clinical management and cause of treatment failure of prostate cancer (PCa) is its molecular, cellular and clinical heterogeneity. Modelling systems that fully recapitulate clinical diversity and resistant phenotypes are urgently required for the development of successful personalised PCa therapies. The advent of the three-dimensional (3D) organoid model has revolutionised preclinical cancer research through reflecting heterogeneity and offering genomic and environmental manipulation that has opened up unparalleled opportunities for applications in disease modelling, high-throughput drug screening and precision medicine.

Human prostate organoid generation and the identification of prostate development drivers using inductive rodent tissues.

The reactivation of developmental genes and pathways during adulthood may contribute to pathogenesis of diseases such as prostate cancer. Analysis of the mechanistic links between development and disease could be exploited to identify signalling pathways leading to disease in the prostate. However, the mechanisms underpinning prostate development require further characterisation to interrogate fully the link between development and disease.

Traumatic arteriovenous fistula from internal maxillary artery following trigeminal balloon compression.

We describe the development of a direct traumatic arteriovenous fistula arising from the internal maxillary artery after an uneventful percutaneous trigeminal balloon compression for trigeminal neuralgia, and its management through embolization and radiosurgery.

Understanding the implementation of 'Making Every Contact Count' (MECC) delivered by healthcare professionals in a mental health hospital: protocol for a pragmatic formative process evaluation.

Background: 'Making Every Contact Count' (MECC) is a public health strategy supporting public-facing workers to use opportunities during routine contacts to enable health behaviour change. A mental health hospital in the North East of England is currently implementing a programme to embed MECC across the hospital supporting weight management ('A Weight Off Your Mind'). Bespoke MECC training has been developed to improve staff confidence in discussing physical activity, healthy eating, and related behaviour change with service users.

A Review of Prostate Organogenesis and a Role for iPSC-Derived Prostate Organoids to Study Prostate Development and Disease.

The prostate is vulnerable to two major age-associated diseases, cancer and benign enlargement, which account for significant morbidity and mortality for men across the globe. Prostate cancer is the most common cancer reported in men, with over 1.2 million new cases diagnosed and 350,000 deaths recorded annually worldwide.

Co-localisation of intra-nuclear membrane type-1 matrix metalloproteinase and hypoxia inducible factor-2α in osteosarcoma and prostate carcinoma cells.

Increased membrane type-1 matrix metalloproteinase (MT1-MMP) expression in osteosarcoma is predictive of poor prognosis and directs bone metastasis in prostate carcinoma. MT1-MMP subcellular localisation varies with oxygen tension, and, therefore, the aim of the present study was to assess protein interactions between MT1-MMP and the hypoxia inducible factors (HIF-1α and HIF-2α). MT1-MMP protein expression was investigated across a panel of cancer cell lines, including a positive and negative control.

Towards an End-to-End Framework of CCTV-Based Urban Traffic Volume Detection and Prediction.

Near real-time urban traffic analysis and prediction are paramount for effective intelligent transport systems. Whilst there is a plethora of research on advanced approaches to study traffic recently, only one-third of them has focused on urban arterials. A ready-to-use framework to support decision making in local traffic bureaus using largely available IoT sensors, especially CCTV, is yet to be developed.

Same day embolisation followed by microsurgical resection of brain arteriovenous malformations: a single centre early experience.

Introduction: The purpose of this paper is to report our experience of treating cerebral arteriovenous malformations (AVM) in adults with pre-operative embolisation and microsurgical resection on the same day during a single anaesthetic at a single centre between April 2016 and December 2018. We included both elective AVM and AVM that had bled acutely.

Methods: We retrospectively analysed data from patients with cerebral AVMs who underwent embolisation followed by microsurgical resection on the same day at a single neurosurgical centre.

IKBKE activity enhances AR levels in advanced prostate cancer via modulation of the Hippo pathway.

Resistance to androgen receptor (AR) targeting therapeutics in prostate cancer (PC) is a significant clinical problem. Mechanisms by which this is accomplished include AR amplification and expression of AR splice variants, demonstrating that AR remains a key therapeutic target in advanced disease. For the first time we show that IKBKE drives AR signalling in advanced PC.

Propagation of human prostate tissue from induced pluripotent stem cells.

Primary culture of human prostate organoids and patient-derived xenografts is inefficient and has limited access to clinical tissues. This hampers their use for translational study to identify new treatments. To overcome this, we established a complementary approach where rapidly proliferating and easily handled induced pluripotent stem cells enabled the generation of human prostate tissue in vivo and in vitro.

BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration.

BRF1 is a rate-limiting factor for RNA Polymerase III-mediated transcription and is elevated in numerous cancers. Here, we report that elevated levels of BRF1 associate with poor prognosis in human prostate cancer. In vitro studies in human prostate cancer cell lines demonstrated that transient overexpression of BRF1 increased cell proliferation whereas the transient downregulation of BRF1 reduced proliferation and mediated cell cycle arrest.

A novel CRISPR-engineered prostate cancer cell line defines the AR-V transcriptome and identifies PARP inhibitor sensitivities.

Resistance to androgen receptor (AR)-targeted therapies in prostate cancer (PC) is a major clinical problem. A key mechanism of treatment resistance in advanced PC is the generation of alternatively spliced forms of the AR termed AR variants (AR-Vs) that are refractory to targeted agents and drive tumour progression. Our understanding of how AR-Vs function is limited due to difficulties in distinguishing their discriminate activities from full-length AR (FL-AR).

The Pioneering Role of GATA2 in Androgen Receptor Variant Regulation Is Controlled by Bromodomain and Extraterminal Proteins in Castrate-Resistant Prostate Cancer.

The androgen receptor (AR) is a key driver of prostate cancer development. Antiandrogens effectively inactivate the AR, but subsequent AR reactivation progresses the disease to castrate-resistant prostate cancer (CRPC). Constitutively active AR splice variants (AR-V) that function unchallenged by current AR-targeted therapies are key drivers of CRPC.

Early mobilisation does not increase the complication rate from unintended lumbar durotomy.

Background: Unintended durotomy is a well-recognised complication of lumbar spine surgery. Reported complications include headaches, intracranial haematomata, pseudomeningocoele and infection. Methods of intraoperative repair vary and although post-operative flat bed rest is advocated by some, there is no consensus on duration.