Evolocumab in metastatic castration-resistant prostate cancer: study protocol for a single-arm, phase II trial, and initial experience with use of a validated lipid biomarker to direct therapy.

Background: Despite advances in the treatment of metastatic castration-resistant prostate cancer (mCRPC), primary and secondary resistance to current therapies remains. Elevated circulating sphingolipids are associated with poor outcomes in patients with mCRPC, including therapeutic resistance and shorter overall survival. PCPro is a clinically accessible, regulatory compliant plasma lipid biomarker of poor prognosis in mCRPC, which incorporates prognostic sphingolipids.

A pupillary contrast response in mice and humans: Neural mechanisms and visual functions.

In the pupillary light response (PLR), increases in ambient light constrict the pupil to dampen increases in retinal illuminance. Here, we report that the pupillary reflex arc implements a second input-output transformation; it senses temporal contrast to enhance spatial contrast in the retinal image and increase visual acuity. The pupillary contrast response (PCoR) is driven by rod photoreceptors via type 6 bipolar cells and M1 ganglion cells.

Characterization of a canine freeze-dried platelet-derived hemostatic agent: A preclinical model for surgical and traumatic hemorrhage.

Introduction: A freeze-dried, platelet-derived hemostatic agent (FPH) was developed for acute hemorrhage. The canine product (cFPH) was developed for use in preclinical models supporting human product (hFPH) investigations.

Materials And Methods: A carotid artery bypass graft (CABG) study in dogs compared 3 dosages of cFPH to canine liquid stored platelets (cLSP) and vehicle (VEH) control groups.

Predation without direction selectivity.

Across the animal kingdom, visual predation relies on motion-sensing neurons in the superior colliculus (SC) and its orthologs. These neurons exhibit complex stimulus preferences, including direction selectivity, which is thought to be critical for tracking the unpredictable escape routes of prey. The source of direction selectivity in the SC is contested, and its contributions to predation have not been tested experimentally.

Nutritional care pathways in cancer patients with malignant bowel obstruction: A retrospective multi-centre study.

Introduction: Variation in access to parenteral nutrition (PN) in patients with intestinal failure secondary to malignant bowel obstruction (MBO) exists due to differing practice, beliefs and resource access. We aimed to examine differences in nutritional care pathways and outcomes, by referral to nutrition team for PN in patients with MBO.

Methods: This is a retrospective cohort study of MBO adults admitted to eight UK hospitals within a year and 1 year follow-up.

An Interpretable Classification Model Using Gluten-Specific TCR Sequences Shows Diagnostic Potential in Coeliac Disease.

Coeliac disease (CeD) is a T-cell mediated enteropathy triggered by dietary gluten which remains substantially under-diagnosed around the world. The diagnostic gold-standard requires histological assessment of intestinal biopsies taken at endoscopy while consuming a gluten-containing diet. However, there is a lack of concordance between pathologists in histological assessment, and both endoscopy and gluten challenge are burdensome and unpleasant for patients.

Mechanisms of action of an investigational new freeze-dried platelet-derived hemostatic product.

Background: A safe and efficacious hemostatic product with a long shelf-life is needed to reduce mortality from hemorrhage due to trauma and improve surgical outcomes for persons with platelet deficiency or dysfunction. Thrombosomes, a trehalose-stabilized, leukoreduced, pooled blood group-O freeze-dried platelet-derived hemostatic (FPH) with a 3-year shelf-life, may satisfy this need.

Objectives: To characterize the mechanism of action of FPH.

The first human normative ranges and biomarker performance of dimethylguanidino valeric acid isoforms in fatty liver disease.

We have recently determined dimethylguanidino valeric acid (DMGV) to be a novel biomarker of liver injury in non-alcoholic fatty liver disease (NAFLD) and an independent predictor of incident diabetes over a decade in advance. DMGV consists of two stereo-isomers, asymmetric dimethylguanidino valeric acid (ADGV) and symmetric dimethylguanidino valeric acid (SDGV). Here we report, for the first time, the upper limits of normal of both isomers in humans at the accepted 5.

Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo.

Retinal ganglion cell (RGC) degeneration drives vision loss in blinding conditions. RGC death is often triggered by axon degeneration in the optic nerve. Here, we study the contributions of dynamic and homeostatic Ca levels to RGC death from axon injury.

Quality assurance programs for vitamin A and E in serum: are we doing enough to assess laboratory performance?

Objectives: Monitoring serum vitamin A (retinol) and vitamin E (α-tocopherol) concentrations is common practice for assessing nutritional status. Measurement of these vitamins can be challenging due to several factors. Whilst the RCPAQAP Vitamins: Serum Program assists participating laboratories in harmonisation, the materials provided do not contain the analogues of retinol and α-tocopherol that may be present in real patient samples.

Differential absolute plasma IL-6 concentrations between two immunoassay platforms in intensive care unit patients with COVID-19.

Explore whether plasma IL-6 levels are similar across biomarker platforms and association with COVID-19 clinical outcomes. Plasma IL-6 concentrations were measured on 191 COVID-19 patients using the Roche Elecsys IL-6 assay and the Meso Scale Discovery assay. Correlation of IL-6 levels between platforms was high (r = 0.

Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity.

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize microbial metabolites through a semi-invariant T cell receptor (TCR). Major questions remain regarding the extent of human MAIT cell functional and clonal diversity. To address these, we analyzed the single-cell transcriptome and TCR repertoire of blood and liver MAIT cells and developed functional RNA-sequencing, a method to integrate function and TCR clonotype at single-cell resolution.

Biomarker Signatures of Severe Acute Kidney Injury in a Critically Ill Cohort of COVID-19 and Non-COVID-19 Acute Respiratory Illness.

Unlabelled: Kidney and lung injury are closely inter-related during acute respiratory illness, but the molecular risk factors that these organ injuries share are not well defined.

Objectives: We identified plasma biomarkers associated with severe acute kidney injury (AKI) during acute respiratory illness, and compared them to biomarkers associated with severe acute respiratory failure (ARF).

Design Settings And Participants: Prospective observational cohort study enrolling March 2020 through May 2021, at three hospitals in a large academic health system.

LC-MS/MS analysis of erythrocyte phosphatidylethanol in haematocrit-corrected whole blood versus isolated erythrocytes: Results of an inter-laboratory comparison.

Phosphatidylethanol (PEth) is a non-oxidative metabolite of alcohol (ethanol), which is a sensitive and specific indicator of historic ethanol consumption. Although PEth production from ethanol is catalysed by the ubiquitous enzyme phospholipase D, it resides mainly within the erythrocyte compartment of the blood. PEth analysis has been reported in different preparations of whole blood, representing one of the barriers of inter-laboratory comparisons.

A liquid chromatography tandem mass spectrometry method for plasma glucagon.

Glucagon is a peptide involved in controlling the body's blood glucose levels. The majority of analytical methods used for its quantitation are based on immunoassays that suffer from cross-reactivity with other peptides. For accurate routine analysis a liquid chromatography tandem mass spectrometry (LC-MSMS) was developed.

A comparison of machine learning methods to classify radioactive elements using prompt-gamma-ray neutron activation data.

The detection of illicit radiological materials is critical to establishing a robust second line of defence in nuclear security. Neutron-capture prompt-gamma activation analysis (PGAA) can be used to detect multiple radioactive materials across the entire Periodic Table. However, long detection times and a high rate of false positives pose a significant hindrance in the deployment of PGAA-based systems to identify the presence of illicit substances in nuclear forensics.

Not all roses are sweet-Pediatric ependymoma.

Ependymomas are rare malignant neoplasms that originate from radial glial cells within the central nervous system. Within pediatric central nervous tumors, ependymomas constitute the third most common entity with the majority occurring within the posterior fossa. Over the past decade, there have been monumental strides in classifying and grading central nervous tumors, specifically ependymomas.

Integrated psychological care services within seizure settings: Key components and implementation factors among example services in four ILAE regions: A report by the ILAE Psychiatry Commission.

Mental health comorbidities are prevalent and problematic in patients with seizures but often suboptimally managed. To address common gaps in care, the Integrated Mental Health Care Pathways Task Force of the International League Against Epilepsy (ILAE) Psychiatry Commission was tasked with providing education and guidance on the integration of mental health management (e.g.

PCPro: a clinically accessible, circulating lipid biomarker signature for poor-prognosis metastatic prostate cancer.

Background: Using comprehensive plasma lipidomic profiling from men with metastatic castration-resistant prostate cancer (mCRPC), we have previously identified a poor-prognostic lipid profile associated with shorter overall survival (OS). In order to translate this biomarker into the clinic, these men must be identifiable via a clinically accessible, regulatory-compliant assay.

Methods: A single regulatory-compliant liquid chromatography-mass spectrometry assay of candidate lipids was developed and tested on a mCRPC Discovery cohort of 105 men.

Design of the Randomized Controlled Trial Comparing Dimethyl Sulfoxide Cryopreserved Platelets to Liquid Stored Platelets in Patients Undergoing Cardiopulmonary Bypass Surgery.

Objective: Dimethylsulfoxide-cryopreserved platelets are being evaluated for treatment of acute hemorrhage in patients with thrombocytopenia or platelet dysfunction when liquid stored platelets are unavailable. Patients undergoing cardiac surgery with cardiopulmonary bypass with risk factors for significant bleeding represent a population for which determining efficacy and safety of cryopreserved platelets is ideal in the clinical trial setting. The primary objective is to compare blood loss in cardiopulmonary bypass patients receiving cryopreserved platelets or liquid stored platelets.

Dementia lifestyle coach pilot program.

Objectives: This study aimed to conduct a feasibility pilot of the Dementia Lifestyle Coach program; an individual coaching and counselling program for people recently diagnosed with dementia, to help them to adjust to the diagnosis and live well.

Methods: A randomised controlled pilot trial (n = 11) with wait-list control group was undertaken over 12 months. Intervention group participants received immediate personalised counselling from a registered psychologist and monthly support (face-to-face or by telephone) from a trained peer mentor living with dementia.