Peptide-Purified Anti-N-methyl-D-aspartate Receptor (NMDAR) Autoantibodies Have Inhibitory Effect on Long-Term Synaptic Plasticity.

Recent studies, typically using patient cerebrospinal fluid (CSF), have suggested that different autoantibodies (Aabs) acting on their respective receptors, may underlie neuropsychiatric disorders. The GluN1 (NR1) subunit of the N-methyl-D-aspartate receptor (NMDAR) has been identified as a target of anti-NMDAR Aabs in a number of central nervous system (CNS) diseases, including encephalitis and autoimmune epilepsy. However, the role or the nature of Aabs responsible for effects on neuronal excitability and synaptic plasticity is yet to be established fully.

Compressed sensing reconstruction for high-SNR, rapid dissolved Xe gas exchange MRI.

Purpose: Three-dimensional hyperpolarized Xe gas exchange imaging suffers from low SNR and long breath-holds, which could be improved using compressed sensing (CS). The purpose of this work was to assess whether gas exchange ratio maps are quantitatively preserved in CS-accelerated dissolved-phase Xe imaging and to investigate the feasibility of CS-dissolved Xe imaging with reduced-cost natural abundance (NA) xenon.

Methods: Xe gas exchange imaging was performed at 1.

"My Dead Body": Development, production, and reception of a documentary that publicly displays the dissection of a human donor.

Recently, there has been an emphasis on keeping the study of anatomy using donor material confined to the domain of medical and allied healthcare professionals. Given the abundance of both accurate and inaccurate information online, coupled with a heightened focus on health following the COVID-19 pandemic, one may question whether it is time to review who can access learning anatomy using donors. In 2019, Brighton and Sussex Medical School (BSMS) obtained a Human Tissue Authority Public Display license with the aim of broadening the reach of who could be taught using donor material.

Icarust, a real-time simulator for Oxford Nanopore adaptive sampling.

Motivation: Oxford Nanopore Technologies (ONT) sequencers enable real-time generation of sequence data, which allows for concurrent analysis during a run. Adaptive sampling leverages this real-time capability in extremis, rejecting or accepting reads for sequencing based on assessment of the sequence from the start of each read. This functionality is provided by ONT's software, MinKNOW (Oxford Nanopore Technologies).

The Stabilization of S100A9 Structure by Calcium Inhibits the Formation of Amyloid Fibrils.

The calcium-binding protein S100A9 is recognized as an important component of the brain neuroinflammatory response to the onset and development of neurodegenerative disease. S100A9 is intrinsically amyloidogenic and in vivo co-aggregates with amyloid-β peptide and α-synuclein in Alzheimer's and Parkinson's diseases, respectively. It is widely accepted that calcium dyshomeostasis plays an important role in the onset and development of these diseases, and studies have shown that elevated levels of calcium limit the potential for S100A9 to adopt a fibrillar structure.

Incivility in healthcare: the impact of poor communication.

Incivility is a common issue within healthcare in the UK and internationally. Experienced by at least one-third of staff within the UK National Health Service, incivility has been demonstrated to have significant negative implications on both patient care and healthcare staff. These include contributing to direct medical errors, diagnostic inaccuracy and team communication, with a large associated cost burden, while for staff it has significant negative impacts on retention, productivity and morale.

A framework for real-time monitoring, analysis and adaptive sampling of viral amplicon nanopore sequencing.

The ongoing SARS-CoV-2 pandemic demonstrates the utility of real-time sequence analysis in monitoring and surveillance of pathogens. However, cost-effective sequencing requires that samples be PCR amplified and multiplexed barcoding onto a single flow cell, resulting in challenges with maximising and balancing coverage for each sample. To address this, we developed a real-time analysis pipeline to maximise flow cell performance and optimise sequencing time and costs for any amplicon based sequencing.

Longitudinal Lung Function Assessment of Patients Hospitalized With COVID-19 Using H and Xe Lung MRI.

Background: Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pulmonary changes in these patients remains unclear.

Research Question: Do patients hospitalized with COVID-19 without evidence of architectural distortion on structural imaging exhibit longitudinal improvements in lung function measured by using H and Xe MRI between 6 and 52 weeks following hospitalization?

Study Design And Methods: Patients who were hospitalized with COVID-19 pneumonia underwent a pulmonary H and Xe MRI protocol at 6, 12, 25, and 51 weeks following hospital admission in a prospective cohort study between November 2020 and February 2022.

Anti-AMPA Receptor Autoantibodies Reduce Excitatory Currents in Rat Hippocampal Neurons.

The GluR3 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) has been identified as a target for autoantibodies (Aabs) in autoimmune encephalopathy and other diseases. Recent studies have proposed mechanisms by which these Aabs act, but their exact role in neuronal excitability is yet to be established. Patient Aabs have been shown to bind to specific regions within the GluR3 subunit.

Evolution of treatment patterns and survival outcomes in patients with advanced non-small cell lung cancer treated at Frankfurt University Hospital in 2012-2018.

Background: Immune checkpoint inhibitors (ICIs) have improved outcomes for patients with advanced non-small cell lung cancer (NSCLC) versus chemotherapy in clinical trials. In Germany, ICIs have been used clinically since 2015 for patients with advanced/metastatic NSCLC without epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) aberrations. As part of I-O Optimise, a multinational research program utilizing real-world data on thoracic malignancies, we describe real-world treatment patterns and survival following reimbursement of ICIs for advanced NSCLC in Germany.

Dynamic, adaptive sampling during nanopore sequencing using Bayesian experimental design.

Nanopore sequencers can select which DNA molecules to sequence, rejecting a molecule after analysis of a small initial part. Currently, selection is based on predetermined regions of interest that remain constant throughout an experiment. Sequencing efforts, thus, cannot be re-focused on molecules likely contributing most to experimental success.

CD1a promotes systemic manifestations of skin inflammation.

Inflammatory skin conditions are increasingly recognised as being associated with systemic inflammation. The mechanisms connecting the cutaneous and systemic disease are not well understood. CD1a is a virtually monomorphic major histocompatibility complex (MHC) class I-like molecule, highly expressed by skin and mucosal Langerhans cells, and presents lipid antigens to T-cells.

Oligomerization processes limit photoactivation and recovery of the orange carotenoid protein.

The orange carotenoid protein (OCP) is a photoactive protein involved in cyanobacterial photoprotection by quenching of the excess of light-harvested energy. The photoactivation mechanism remains elusive, in part due to absence of data pertaining to the timescales over which protein structural changes take place. It also remains unclear whether or not oligomerization of the dark-adapted and light-adapted OCP could play a role in the regulation of its energy-quenching activity.

Understanding beliefs, preferences and actions amongst potential body donors.

Body donation is a prosocial act providing a unique learning experience to students, ultimately impacting on patient care and science. With an increasing number of training professionals, there is an increasing need for body donors, yet little is understood about donors' beliefs and preferences. A four-center study aimed to understand donors' perceptions, 843 responses highlighted a significant relationship between completing a body donor consent form and being both an organ donor and having ever donated blood (p < 0.

Trends in treatment patterns and survival outcomes in advanced non-small cell lung cancer: a Canadian population-based real-world analysis.

Background: As part of the multi-country I-O Optimise research initiative, this population-based study evaluated real-world treatment patterns and overall survival (OS) in patients treated for advanced non-small cell lung cancer (NSCLC) before and after public reimbursement of immuno-oncology (I-O) therapies in Alberta province, Canada.

Methods: This study used data from the Oncology Outcomes (O2) database, which holds information for ~ 4.5 million residents of Alberta.

minoTour, real-time monitoring and analysis for nanopore sequencers.

Summary: minoTour offers a Laboratory Informations Management System (LIMS) system for Oxford Nanopore Technology sequencers, with real-time metrics and analysis available permanently for review. Integration of unique real-time automated analysis can reduce the time required to answer biological questions, including mapping and classification of sequence while a run is in progress. Real-time sequence data require new methods of analysis which do not wait for the completion of a run and minoTour provides a framework to allow users to exploit these features.

Treatment and outcomes for early non-small-cell lung cancer: a retrospective analysis of a Portuguese hospital database.

Aim: This observational study evaluated treatment patterns and survival for patients with stage I-IIIA non-small-cell lung cancer (NSCLC).

Materials & Methods: Adults newly diagnosed with NSCLC in 2012-2016 at IPO-Porto hospital were included. Treatment data were available for patients diagnosed in 2015-2016.

A conformation-selective monoclonal antibody against a small molecule-stabilised signalling-deficient form of TNF.

We have recently described the development of a series of small-molecule inhibitors of human tumour necrosis factor (TNF) that stabilise an open, asymmetric, signalling-deficient form of the soluble TNF trimer. Here, we describe the generation, characterisation, and utility of a monoclonal antibody that selectively binds with high affinity to the asymmetric TNF trimer-small molecule complex. The antibody helps to define the molecular dynamics of the apo TNF trimer, reveals the mode of action and specificity of the small molecule inhibitors, acts as a chaperone in solving the human TNF-TNFR1 complex crystal structure, and facilitates the measurement of small molecule target occupancy in complex biological samples.

Readfish enables targeted nanopore sequencing of gigabase-sized genomes.

Nanopore sequencers can be used to selectively sequence certain DNA molecules in a pool by reversing the voltage across individual nanopores to reject specific sequences, enabling enrichment and depletion to address biological questions. Previously, we achieved this using dynamic time warping to map the signal to a reference genome, but the method required substantial computational resources and did not scale to gigabase-sized references. Here we overcome this limitation by using graphical processing unit (GPU) base-calling.

Carbonic anhydrase inhibition in X-linked retinoschisis: An eye on the photoreceptors.

The retinoschisin protein is encoded on the short arm of the X-chromosome by RS1, is expressed abundantly in photoreceptor inner segments and in bipolar cells, and is secreted as an octamer that maintains the structural integrity of the retina. Mutations in RS1 lead to X-linked retinoschisis (XLRS), a disease characterized by the formation of cystic spaces between boys' retinal layers that frequently present in ophthalmoscopy as a "spoke-wheel" pattern on their maculae and by progressively worsening visual acuity (VA). There is no proven therapy for XLRS, but there is mixed evidence that carbonic anhydrase inhibitors (CAIs) produce multiple beneficial effects, including improved VA and decreased volume of cystic spaces.

European Forensic Veterinary Pathology Comes of Age.

During the mid-1700s, development of the veterinary profession was largely focussed on equine medicine and surgery. Subsequently, rather erratic development encompassed other species and eventually led to specialization in different disciplines. Teaching of veterinary pathology was well established in Europe and North America by the late 19 century.

The Fovea in Retinopathy of Prematurity.

Purpose: Because preterm birth and retinopathy of prematurity (ROP) are associated with poor visual acuity (VA) and altered foveal development, we evaluated relationships among the central retinal photoreceptors, postreceptor retinal neurons, overlying fovea, and VA in ROP.

Methods: We obtained optical coherence tomograms (OCTs) in preterm born subjects with no history of ROP (none; n = 61), ROP that resolved spontaneously without treatment (mild; n = 51), and ROP that required treatment by laser ablation of the avascular peripheral retina (severe; n = 22), as well as in term born control subjects (term; n = 111). We obtained foveal shape descriptors, measured central retinal layer thicknesses, and demarcated the anatomic parafovea using automated routines.

Real-world treatment patterns and survival outcomes for advanced non-small cell lung cancer in the pre-immunotherapy era in Portugal: a retrospective analysis from the I-O Optimise initiative.

Background: As part of the multinational I-O Optimise research initiative, this retrospective cohort study of patients with advanced non-small cell lung cancer (NSCLC) evaluated real-world treatment patterns and survival prior to immunotherapy reimbursement in Portugal.

Methods: This study utilized a database held by IPO-Porto, Portugal's largest oncology hospital. Adult patients diagnosed with stage IIIB or IV NSCLC from January 2012 to December 2016 at IPO-Porto, with follow-up to June 2017, were included.