Publications by authors named "Steven R"

Background: The marine environment boasts distinctive physical, chemical, and biological characteristics. While numerous studies have delved into the microbial ecology and biological potential of the marine environment, exploration of genetically encoded, deep-sea sourced secondary metabolites remains scarce. This study endeavors to investigate marine bioproducts derived from deep-sea water samples at a depth of 1,000 m in the Java Trench, Indonesia, utilizing both culture-dependent and whole-genome sequencing methods.

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Background: Triple-negative breast cancer (TNBC) has been documented as the most aggressive subtype of breast cancer. This study aimed to analyze antitumor and protumor immune activities, and their ratios as significant prognostic biomarkers in metastatic TNBC (mTNBC).

Methods: A multicenter cohort study was conducted among 103 de novo mTNBC patients.

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Background: Triple-negative breast cancer (TNBC) is an aggressive cancer subtype, with limited treatments and a high metastasis risk. The varying location of metastasis in TNBC patients often leads to in prognosis in breast cancer. Therefore, this study aimed to investigate the potential association between immune cells profiles in the tumor microenvironment and metastatic patterns.

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Mass spectrometry imaging (MSI) allows for the spatially resolved detection of endogenous and exogenous molecules and atoms in biological samples, typically prepared as thin tissue sections. Desorption electrospray ionization (DESI) is one of the most commonly utilized MSI modalities in preclinical research. DESI ion source technology is still rapidly evolving, with new sprayer designs and heated inlet capillaries having recently been incorporated in commercially available systems.

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Background: Splenectomy is commonly used to treat refractory immune-mediated cytopenia, but there are no established factors that are associated with response to the procedure.

Objectives: A cohort study was conducted to evaluate the hematologic and surgical outcomes of splenectomy in adult patients with immune cytopenias and identify preoperative factors associated with response.

Methods: Data from the Cleveland Clinic Foundation for 1824 patients aged over 18 who underwent splenectomy from 2002 to 2020 were analyzed.

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The genomic landscape of colorectal cancer (CRC) is shaped by inactivating mutations in tumour suppressors such as APC, and oncogenic mutations such as mutant KRAS. Here we used genetically engineered mouse models, and multimodal mass spectrometry-based metabolomics to study the impact of common genetic drivers of CRC on the metabolic landscape of the intestine. We show that untargeted metabolic profiling can be applied to stratify intestinal tissues according to underlying genetic alterations, and use mass spectrometry imaging to identify tumour, stromal and normal adjacent tissues.

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Background: Mammals, globally, are facing population declines. Protecting and breeding threatened populations inside predator-free havens and translocating them back to the wild is commonly viewed as a solution. These approaches can expose predator-naïve animals to predators they have never encountered and as a result, many conservation projects have failed due to the predation of individuals that lacked appropriate anti-predator responses.

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Mass spectrometry imaging (MSI) encompasses a powerful suit of techniques which provide spatially resolved atomic and molecular information from almost any sample type. MSI is now widely used in preclinical research to provide insight into metabolic phenotypes of disease. Typically, fresh-frozen tissue preparations are considered optimal for biological MSI and other traditional preservation methods such as formalin fixation, alone or with paraffin embedding (FFPE), are considered less optimal or even incompatible.

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Microbes in marine ecosystems are known to produce secondary metabolites. One of which are carotenoids, which have numerous industrial applications, hence their demand will continue to grow. This review highlights the recent research on natural carotenoids produced by marine microorganisms.

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The terrestrial, freshwater and marine realms all provide essential ecosystem services in urban environments. However, the services provided by each realm are often considered independently, which ignores the synergies between them and risks underestimating the benefits derived collectively. Greater research collaboration across these realms, and an integrated approach to management decisions can help to support urban developments and restoration projects in maintaining or enhancing ecosystem services.

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Objectives: This study seeks the opinions of qualified doctors on what they feel medical students should learn about otolaryngology. It aims to identify both the content deemed relevant and the performance levels for medical students in otolaryngology.

Methods: A national survey developed from a content analysis of undergraduate otolaryngology curricula from the UK was undertaken, accompanied by a review of the literature and input from an expert group.

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Image resolution in mass spectrometry imaging (MSI) is governed by the sampling probe, the motion of the stage relative to the probe, and the noise inherent for the sample and instrumentation employed. A new image formation model accounting for these variables is presented here. The model shows that the size of the probe, stage velocity, and the rate at which the probe consumes material from the surface govern the amount of blur present in the image.

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Here we show a new and significant application area for mass spectrometry imaging. The potential for fingerprints to reveal drug use has been widely reported, with potential applications in forensics and workplace drug testing. However, one unsolved issue is the inability to distinguish between drug administration and contamination by contact.

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Bacterial pericarditis and empyema due to Cutibacterium acnes has rarely been reported. C.acnes, a normal component of human skin flora, is often considered a contaminant when isolated from body fluids and thus cases may be underreported.

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Article Synopsis
  • * The study highlights that mutant KRAS increases glutamine consumption in cancer cells, which is crucial for their growth and proliferation, and identifies SLC7A5 as a key player in maintaining amino acid levels needed for this process.
  • * Targeting protein synthesis pathways, particularly by inhibiting mTORC1 and deleting SLC7A5, shows promise in slowing down the growth of Kras-mutant tumors, suggesting SLC7A5 could be a valuable therapeutic target for difficult-to-treat CRC cases.
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Mass spectrometry imaging can produce large amounts of complex spectral and spatial data. Such data sets are often analyzed with unsupervised machine learning approaches, which aim at reducing their complexity and facilitating their interpretation. However, choices made during data processing can impact the overall interpretation of these analyses.

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Matrix-assisted laser desorption ionization (MALDI) operated at atmospheric pressure has been shown to be a promising technique for mass spectrometry imaging of biological tissues at high spatial resolution. Recent studies have shown several orders of magnitude improvement in sensitivity afforded by coupling with a low-temperature plasma (LTP) for postionization. In this work we report the first results from "matrix-free" imaging using our atmospheric pressure (AP) transmission mode (TM) (MA)LDI source with LTP postionization.

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Background: Serological assays for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have roles in seroepidemiology, convalescent plasma-testing, antibody durability and vaccine studies. Currently, SARS-CoV-2 serology is performed using serum/plasma collected by venepuncture. Dried blood spot (DBS) testing offers significant advantages as it is minimally invasive, avoids venepuncture with specimens being mailed to the laboratory.

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Atmospheric pressure ionization methods confer a number of advantages over more traditional vacuum based techniques, in particular ease of hyphenation to a range of mass spectrometers. For atmospheric pressure matrix assisted desorption/ionization (AP-MALDI), several ion sources, operating in a range of geometries have been reported. Most of these platforms have, to date, generally demonstrated relatively low ion yields and/or poor ion transmission compared to vacuum sources.

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Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a powerful label-free technique for mapping the spatial distribution of biomolecules directly from tissue. However, like most other MSI techniques, it suffers from low ionization yields and ion suppression effects for biomolecules that might be of interest for a specific application at hand. Recently, a form of laser postionization was introduced (coined MALDI-2) that critically boosts the ion yield for many glyco- and phospholipids by several orders of magnitude and makes the detection of further biomolecular species possible.

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Background: Patients with primary antibody deficiency (PAD) are at increased risk of respiratory tract infections, but our understanding of their nature and consequences remains limited.

Objective: To define the symptomatic and microbial burden of upper airway infection in adults with PAD relative to age-matched controls.

Methods: Prospective 12-month observational study consisting of a daily upper and lower airway symptom score alongside fortnightly nasal swab with molecular detection of 19 pathogen targets.

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Chemical imaging techniques are increasingly being used in combination to achieve a greater understanding of a sample. This is especially true in the case of mass spectrometry imaging (MSI), where the use of different ionization sources allows detection of different classes of molecules across a range of spatial resolutions. There has been significant recent effort in the development of data fusion algorithms that attempt to combine the benefits of multiple techniques, such that the output provides additional information that would have not been present or obvious from the individual techniques alone.

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Aims: An association between antibody deficiency and clozapine use in individuals with schizophrenia has recently been reported. We hypothesised that if clozapine-associated hypogammaglobulinaemia was clinically relevant this would manifest in referral patterns.

Methods: Retrospective case note review of patients referred and assessed by Immunology Centre for Wales (ICW) between January 2005 and July 2018 with extraction of clinical and immunological features for individuals with diagnosis of schizophrenia-like illness.

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Within drug development and pre-clinical trials, a common, significant and poorly understood event is the development of drug-induced lipidosis in tissues and cells. In this manuscript, we describe a mass spectrometry imaging strategy, involving repeated analysis of tissue sections by DESI MS, in positive and negative polarities, using MS and MS/MS modes. We present results of the detected distributions of the administered drug, drug metabolites, lipid molecules and a putative marker of lipidosis, di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate (di-22:6-BMP).

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