Characterization of the immune cell landscape in CRC: Clinical implications of tumour-infiltrating leukocytes in early- and late-stage CRC.

Introduction: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths globally. Tumour-infiltrating leukocytes play an important role in cancers, including CRC. We therefore sought to characterize the impact of tumour-infiltrating leukocytes on CRC prognosis.

One Size Does Not Fit All in Remote Anatomy Teaching.

Anatomical knowledge is central to the advancement of biomedical research and clinical practice and provides the underpinning foundations for many clinical examinations and processes. Anatomy is a very practical and three-dimensional subject, requiring learners to be able to visualise structures within the body and how they interact with each other. Typically, this is taught through a combination of lectures and practical laboratories in which students can interact with human cadaveric material to gain an appreciation of real-life anatomy, often commenting on how these lab sessions really bring their lectures to life.

Increasing Collaborative Discussion in Case-Based Learning Improves Student Engagement and Knowledge Acquisition.

Background: In the transition from academic to clinical learning, the development of clinical reasoning skills and teamwork is essential, but not easily achieved by didactic teaching only. Case-based learning (CBL) was designed to stimulate discussions of genuine clinical cases and diagnoses but in our initial format (CBL'10) remained predominantly tutor-driven rather than student-directed. However, interactive teaching methods stimulate deep learning and consolidate taught material, and we therefore introduced a more collaborative CBL (cCBL), featuring a structured format with discussions in small breakout groups.

Comprehensive genomic and tumour immune profiling reveals potential therapeutic targets in malignant pleural mesothelioma.

Background: Malignant pleural mesothelioma (MPM) has a poor overall survival with few treatment options. Whole genome sequencing (WGS) combined with the immune features of MPM offers the prospect of identifying changes that could inform future clinical trials.

Methods: We analysed somatic mutations from 229 MPM samples, including previously published data and 58 samples that had undergone WGS within this study.

Creation of a novel simple heat mapping method for curriculum mapping, using pathology teaching as the exemplar.

Background: The undergraduate five-year MBChB programme at the University of Glasgow has a high volume of pathology teaching integrated into the course. The ability to better understand what pathology is taught and when, so as to build a picture of the types and depth of pathology topics covered across the programme stages is crucial, especially in a spiral curriculum. A novel method of curriculum mapping, known as curriculum heat mapping, was developed as a way to visualise where and when topics are taught, in an easier to understand format.

Twelve tips for online synchronous small group learning in medical education.

This article was migrated. The article was marked as recommended. Undergraduate medical education relies on a variety of small group learning formats to deliver the curriculum, support collaborative learning, encourage critical thinking, as well as the development of a number of professional, clinical and generic attributes.

Identification of a CD8+ T-cell response to a predicted neoantigen in malignant mesothelioma.

Neoantigens present unique and specific targets for personalized cancer immunotherapy strategies. Given the low mutational burden yet immunotherapy responsiveness of malignant mesothelioma (MM) when compared to other carcinogen-induced malignancies, identifying candidate neoantigens and T cells that recognize them has been a challenge. We used pleural effusions to gain access to MM tumor cells as well as immune cells in order to characterize the tumor-immune interface in MM.

Systems based analysis of human embryos and gene networks involved in cell lineage allocation.

Background: Little is understood of the molecular mechanisms involved in the earliest cell fate decision in human development, leading to the establishment of the trophectoderm (TE) and inner cell mass (ICM) stem cell population. Notably, there is a lack of understanding of how transcriptional networks arise during reorganisation of the embryonic genome post-fertilisation.

Results: We identified a hierarchical structure of preimplantation gene network modules around the time of embryonic genome activation (EGA).

Is the P chemical shift anisotropy of aluminophosphates a useful parameter for NMR crystallography?

The P chemical shift anisotropy (CSA) offers a potential source of new information to help determine the structures of aluminophosphate (AlPO) framework materials. We investigate how to measure the CSAs, which are small (span of ~20-30 ppm) for AlPOs, demonstrating the need for CSA-amplification experiments (often in conjunction with Al and/or H decoupling) at high magnetic field (20.0 T) to obtain accurate values.

Malignant cells from pleural fluids in malignant mesothelioma patients reveal novel mutations.

Objectives: Malignant mesothelioma (MM) is an asbestos related tumour affecting cells of serosal cavities. More than 70% of MM patients develop pleural effusions which contain tumour cells, representing a readily accessible source of malignant cells for genetic analysis. Although common somatic mutations and losses have been identified in solid MM tumours, the characterization of tumour cells within pleural effusions could provide novel insights but is little studied.

O solid-state NMR spectroscopy of ABO oxides: quantitative isotopic enrichment and spectral acquisition?

The potential of O NMR spectroscopy for the investigation of ABO ceramic oxides important in the encapsulation of radioactive waste is demonstrated, with post-synthetic enrichment by exchange with O gas. For YSnO, YTiO and LaSnO pyrochlores, enrichment of the two distinct O species is clearly non quantitative at lower temperatures (∼700 °C and below) and at shorter times, despite these being used in prior work, with preferential enrichment of OAB favoured over that of OA. At higher temperatures, the O NMR spectra suggest that quantitative enrichment has been achieved, but the integrated signal intensities do not reflect the crystallographic 1 : 6 (O1 : O2) ratio until corrected for differences in relaxation rates and, more importantly, the contribution of the satellite transitions.

The use of whole exome sequencing and murine patient derived xenografts as a method of chemosensitivity testing in sarcoma.

Background: Soft tissue and bone sarcoma represent a broad spectrum of different pathology and genetic variance. Current chemotherapy regimens are derived from randomised trials and represent empirical treatment. Chemosensitivity testing and whole exome sequencing (WES) may offer personalized chemotherapy treatment based on genetic mutations.

Investigation of zeolitic imidazolate frameworks using C and N solid-state NMR spectroscopy.

Zeolitic imidazolate frameworks (ZIFs) are a subclass of metal-organic frameworks (MOFs) with extended three-dimensional networks of transition metal nodes (bridged by rigid imidazolate linkers), with potential applications in gas storage and separation, sensing and controlled delivery of drug molecules. Here, we investigate the use of C and N solid-state NMR spectroscopy to characterise the local structure and disorder in a variety of single- and dual-linker ZIFs. In most cases, a combination of a basic knowledge of chemical shifts typically observed in solution-state NMR spectroscopy and the use of dipolar dephasing NMR experiments to reveal information about quaternary carbon species are combined to enable spectral assignment.

Whole exome sequencing of an asbestos-induced wild-type murine model of malignant mesothelioma.

Background: Malignant mesothelioma (MM) is an aggressive cancer of the pleural and peritoneal cavities caused by exposure to asbestos. Asbestos-induced mesotheliomas in wild-type mice have been used extensively as a preclinical model because they are phenotypically identical to their human counterpart. However, it is not known if the genetic lesions in these mice tumours are similar to in the human disease, a prerequisite for any new preclinical studies that target genetic abnormalities.

Phase Composition and Disorder in La(Sn,Ti)O Ceramics: New Insights from NMR Crystallography.

An NMR crystallographic approach, involving the combination of Sn NMR spectroscopy, XRD, and DFT calculations, is demonstrated for the characterization of LaSn Ti O ceramics. A phase change from pyrochlore (LaSnO) to a layered perovskite phase (LaTiO) is predicted (by radius ratio rules) to occur when ≈ 0.95.

Derivation of the human embryonic stem cell line RCM1.

The human embryonic stem cell line RCM-1 was derived from a failed to fertilise egg undergoing parthenogenetic stimulation. The cell line shows normal pluripotency marker expression and differentiation to three germ layers in vitro and in vivo. It has a normal 46XX female karyotype and microsatellite PCR identity, HLA and blood group typing data is available.

Strong spontaneous tumor neoantigen responses induced by a natural human carcinogen.

A key to improving cancer immunotherapy will be the identification of tumor-specific "neoantigens" that arise from mutations and augment the resultant host immune response. In this study we identified single nucleotide variants (SNVs) by RNA sequencing of asbestos-induced murine mesothelioma cell lines AB1 and AB1-HA. Using the NetMHCpan 2.

Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma.

Malignant mesothelioma (MM) is a uniformly fatal tumour caused predominantly by exposure to asbestos. It is not known why some exposed individuals get mesothelioma and others do not. There is some epidemiological evidence of host susceptibility.

New insights into phase distribution, phase composition and disorder in Y2(Zr,Sn)2O7 ceramics from NMR spectroscopy.

A combination of (89)Y and (119)Sn NMR spectroscopy and DFT calculations are used to investigate phase evolution, local structure and disorder in Y2Zr2-xSnxO7 ceramics, where a phase change is predicted, from pyrochlore to defect fluorite, with increasing Zr content. The ability of NMR to effectively probe materials that exhibit positional and compositional disorder provides insight into the atomic-scale structure in both ordered and disordered phases and, by exploiting the quantitative nature of the technique, we are able to determine detailed information on the composition of the phase(s) present and the average coordination number (and next-nearest neighbour environment) of the cations. In contrast to previous studies, a more complex picture of the phase variation with composition emerges, with single-phase pyrochlore found only for the Sn end member, and a single defect fluorite phase only for x = 0 to 0.

New methods and applications in solid-state NMR spectroscopy of quadrupolar nuclei.

Solid-state nuclear magnetic resonance (NMR) spectroscopy has long been established as offering unique atomic-scale and element-specific insight into the structure, disorder, and dynamics of materials. NMR spectra of quadrupolar nuclei (I > (1)/2) are often perceived as being challenging to acquire and to interpret because of the presence of anisotropic broadening arising from the interaction of the electric field gradient and the nuclear electric quadrupole moment, which broadens the spectral lines, often over several megahertz. Despite the vast amount of information contained in the spectral line shapes, the problems with sensitivity and resolution have, until very recently, limited the application of NMR spectroscopy of quadrupolar nuclei in the solid state.

Calculating NMR parameters in aluminophosphates: evaluation of dispersion correction schemes.

Periodic density functional theory (DFT) calculations have recently emerged as a popular tool for assigning solid-state nuclear magnetic resonance (NMR) spectra. However, in order for the calculations to yield accurate results, accurate structural models are also required. In many cases the structural model (often derived from crystallographic diffraction) must be optimised (i.

Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum.

The MSLN gene products, soluble mesothelin and megakaryocyte potentiating factor (MPF), are being investigated as biomarkers for the asbestos-related cancer malignant mesothelioma (MM). Pleural fluid biomarkers of MM can be elevated when serum levels remain normal. The aim of this study was to determine if this was true for MPF and to compare levels of mesothelin.

Global gene expression profiling of individual human oocytes and embryos demonstrates heterogeneity in early development.

Early development in humans is characterised by low and variable embryonic viability, reflected in low fecundity and high rates of miscarriage, relative to other mammals. Data from assisted reproduction programmes provides additional evidence that this is largely mediated at the level of embryonic competence and is highly heterogeneous among embryos. Understanding the basis of this heterogeneity has important implications in a number of areas including: the regulation of early human development, disorders of pregnancy, assisted reproduction programmes, the long term health of children which may be programmed in early development, and the molecular basis of pluripotency in human stem cell populations.