Proteomic Characterisation of Heart Failure Reveals a Unique Molecular Phenotype for Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a disease, which is difficult to diagnose at an early stage and for which there is a pressing need for more effective treatment options. The purpose of this study was to compare the molecular profile of HCM to that of ischaemic cardiomyopathy (ISCM) and dilated cardiomyopathy (DCM) for identification of protein and pathway targets that could support the development of better diagnostic and treatment options for HCM. A high-throughput mass spectrometry workflow was applied to achieve deep quantitative coverage of left ventricular tissue from HCM, DCM, ISCM and non-heart-failure control patients.

Single-Cell RNA Sequencing Reveals Cardiac Fibroblast-Specific Transcriptomic Changes in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is the most common cause of heart failure, with a complex aetiology involving multiple cell types. We aimed to detect cell-specific transcriptomic alterations in DCM through analysis that leveraged recent advancements in single-cell analytical tools. Single-cell RNA sequencing (scRNA-seq) data from human DCM cardiac tissue were subjected to an updated bioinformatic workflow in which unsupervised clustering was paired with reference label transfer to more comprehensively annotate the dataset.

Serum HCoV-spike specific antibodies do not protect against subsequent SARS-CoV-2 infection in children and adolescents.

SARS-CoV-2 infections in children are generally asymptomatic or mild and rarely progress to severe disease and hospitalization. Why this is so remains unclear. Here we explore the potential for protection due to pre-existing cross-reactive seasonal coronavirus antibodies and compare the rate of antibody decline for nucleocapsid and spike protein in serum and oral fluid against SARS-CoV-2 within the pediatric population.

Comparison of frequency domain and time domain methods for the numerical simulation of contactless ultrasonic cavitation.

The use of a top-mounted electromagnetic induction coil has been demonstrated as a contactless alternative to traditional ultrasonic treatment (UST) techniques that use an immersed mechanical sonotrode for the treatment of metals in the liquid state. This method offers similar benefits to existing UST approaches, including degassing, grain refinement, and dispersion of nanoparticles, while also preventing contact contamination due to erosion of the sonotrode. Contactless treatment potentially extends UST to high temperature or reactive melts.

Circulating biomarkers for management of cancer therapeutics-related cardiac dysfunction.

Cancer therapeutics-related cardiac dysfunction (CTRCD) has emerged as a major cause of morbidity and mortality in cancer survivors. Effective clinical management of CTRCD is impeded by a lack of sensitive diagnostic and prognostic strategies. Circulating molecular markers could potentially address this need as they are often indicative of cardiac stress before cardiac damage can be detected clinically.

Clinical features and predictive biomarkers for bladder cancer in patients with type 2 diabetes presenting with haematuria.

Aims: To identify clinical features and protein biomarkers associated with bladder cancer (BC) in individuals with type 2 diabetes mellitus presenting with haematuria.

Materials And Methods: Data collected from the Haematuria Biomarker (HaBio) study was used in this analysis. A matched sub-cohort of patients with type 2 diabetes and patients without diabetes was created based on age, sex, and BC diagnosis, using approximately a 1:2 fixed ratio.

Enhancement of Mechanical Properties of Pure Aluminium through Contactless Melt Sonicating Treatment.

A new contactless ultrasonic sonotrode method was previously designed to provide cavitation conditions inside liquid metal. The oscillation of entrapped gas bubbles followed by their final collapse causes extreme pressure changes leading to de-agglomeration and the dispersion of oxide films. The forced wetting of particle surfaces and degassing are other mechanisms that are considered to be involved.

Multiplexed measurement of candidate blood protein biomarkers of heart failure.

Aims: There is a critical need for better biomarkers so that heart failure can be diagnosed at an earlier stage and with greater accuracy. The purpose of this study was to design a robust mass spectrometry (MS)-based assay for the simultaneous measurement of a panel of 35 candidate protein biomarkers of heart failure, in blood. The overall aim was to evaluate the potential clinical utility of this biomarker panel for prediction of heart failure in a cohort of 500 patients.

Clinical proteomics for prostate cancer: understanding prostate cancer pathology and protein biomarkers for improved disease management.

Following the introduction of routine Prostate Specific Antigen (PSA) screening in the early 1990's, Prostate Cancer (PCa) is often detected at an early stage. There are also a growing number of treatment options available and so the associated mortality rate is generally low. However, PCa is an extremely complex and heterogenous disease and many patients suffer disease recurrence following initial therapy.

Seroprevalence of SARS-CoV-2 antibodies in children: a prospective multicentre cohort study.

Background: Studies based on molecular testing of oral/nasal swabs underestimate SARS-CoV-2 infection due to issues with test sensitivity, test timing and selection bias. The objective of this study was to report the presence of SARS-CoV-2 antibodies, consistent with previous infection.

Design: This multicentre observational cohort study, conducted between 16 April to 3 July 2020 at 5 UK sites, recruited children of healthcare workers, aged 2-15 years.

Tetranectin, a potential novel diagnostic biomarker of heart failure, is expressed within the myocardium and associates with cardiac fibrosis.

Heart failure (HF) screening strategies require biomarkers to predict disease manifestation to aid HF surveillance and management programmes. The aim of this study was to validate a previous proteomics discovery programme that identified Tetranectin as a potential HF biomarker candidate based on expression level changes in asymptomatic patients at future risk for HF development. The initial study consisted of 132 patients, comprising of HF (n = 40), no-HF controls (n = 60), and cardiac surgery patients (n = 32).

Thermoelectric magnetohydrodynamic control of melt pool dynamics and microstructure evolution in additive manufacturing.

Large thermal gradients in the melt pool from rapid heating followed by rapid cooling in metal additive manufacturing generate large thermoelectric currents. Applying an external magnetic field to the process introduces fluid flow through thermoelectric magnetohydrodynamics. Convective transport of heat and mass can then modify the melt pool dynamics and alter microstructural evolution.

Acoustic resonance for contactless ultrasonic cavitation in alloy melts.

Contactless ultrasound is a novel, easily implemented, technique for the Ultrasonic Treatment (UST) of liquid metals. Instead of using a vibrating sonotrode probe inside the melt, which leads to contamination, we consider a high AC frequency electromagnetic coil placed close to the metal free surface. The coil induces a rapidly changing Lorentz force, which in turn excites sound waves.

Contactless Ultrasonic Cavitation in Alloy Melts.

A high frequency tuned electromagnetic induction coil is used to induce ultrasonic pressure waves leading to cavitation in alloy melts. This presents an alternative '' approach to conventional immersed probe techniques. The method can potentially offer the same benefits of traditional ultrasonic treatment (UST) such as degassing, microstructure refinement and dispersion of particles, but avoids melt contamination due to probe erosion prevalent in immersed sonotrodes, and it can be used on higher temperature and reactive alloys.

Probing the prostate tumour microenvironment II: Impact of hypoxia on a cell model of prostate cancer progression.

Approximately one in six men are diagnosed with Prostate Cancer every year in the Western world. Although it can be well managed and non-life threatening in the early stages, over time many patients cease to respond to treatment and develop castrate resistant prostate cancer (CRPC). CRPC represents a clinically challenging and lethal form of prostate cancer.

Probing the prostate tumour microenvironment I: impact of glucose deprivation on a cell model of prostate cancer progression.

In the developed world, prostate cancer is the most common cancer diagnosis in men. Although prostate cancer initially presents as a non life-threatening disease, 90% of patients will develop castration resistant prostate cancer (CRPC), which preludes distant metastasis and is largely accountable for prostate cancer associated deaths. This is because as yet, there are no viable molecular therapeutic targets for effective treatment of CRPC.

Pathology-Driven Comprehensive Proteomic Profiling of the Prostate Cancer Tumor Microenvironment.

Prostate cancer is the second most common cancer in men worldwide. Gleason grading is an important predictor of prostate cancer outcomes and is influential in determining patient treatment options. Clinical decisions based on a Gleason score of 7 are difficult as the prognosis for individuals diagnosed with Gleason 4+3 cancer is much worse than for those diagnosed with Gleason 3+4 cancer.

Proteomes, Their Compositions and Their Sources.

Biological samples of human and animal origin are utilized in research for many purposes and in a variety of scientific fields, including mass spectrometry-based proteomics. Various types of samples, including organs, tissues, cells, body fluids such as blood, plasma, cerebrospinal fluid, saliva and semen, can be collected from humans or animals and processed for proteomics analysis. Depending on the physiological state and sample origin, collected samples are used in research and diagnostics for different purposes.

The Role of Proteomics in Biomarker Development for Improved Patient Diagnosis and Clinical Decision Making in Prostate Cancer.

Prostate Cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Although increased expression of prostate-specific antigen (PSA) is an effective indicator for the recurrence of PCa, its intended use as a screening marker for PCa is of considerable controversy. Recent research efforts in the field of PCa biomarkers have focused on the identification of tissue and fluid-based biomarkers that would be better able to stratify those individuals diagnosed with PCa who (i) might best receive no treatment (active surveillance of the disease); (ii) would benefit from existing treatments; or (iii) those who are likely to succumb to disease recurrence and/or have aggressive disease.

Profiling the tumor microenvironment proteome in prostate cancer using laser capture microdissection coupled to LC⿿MS⿿A technical report.

Laser capture microdissection (LCM) allows microscopic procurement of specific cell types from tissue sections. Here, we present an optimized workflow for coupling LCM to LC⿿MS/MS including: sectioning of tissue, a standard LCM workflow, protein digestion and advanced LC⿿MS/MS. Soluble proteins extracted from benign epithelial cells, their associated stroma, tumor epithelial cells and their associated stromal cells from a single patient tissue sample were digested and profiled using advanced LC⿿MS/MS.

Discovery and Longitudinal Evaluation of Candidate Protein Biomarkers for Disease Recurrence in Prostate Cancer.

When compared with hormonal therapy alone, treatment with combined hormone and radiation therapy (CHRT) gives improved disease-specific survival outcomes for patients with prostate cancer; however, a significant number of CHRT patients still succumb to recurrent disease. The purpose of this study was to use longitudinal patient samples obtained as part of an ongoing noninterventional clinical trial (ICORG06-15) to identify and evaluate a potential serum protein signature of disease recurrence. Label-free LC-MS/MS based protein discovery was undertaken on depleted serum samples from CHRT patients who showed evidence of disease recurrence (n = 3) and time-matched patient controls (n = 3).