Neutral hydrolysis of poly(ethylene terephthalate) catalysed by highly active terephthalate-based ionic liquids at low loadings.

Novel ionic liquid catalysts comprising terephthalate anions are capable of promoting the neutral hydrolysis of relatively large flake sizes of poly(ethylene terephthalate) at 0.5 mol% loading (200 °C, 4 h, 94% yield) without either attendant product inhibition or product contamination by protonated catalyst. Catalysts with large, lipophilic phosphonium cations outperform more polar variants.

Tumour purity assessment with deep learning in colorectal cancer and impact on molecular analysis.

Tumour content plays a pivotal role in directing the bioinformatic analysis of molecular profiles such as copy number variation (CNV). In clinical application, tumour purity estimation (TPE) is achieved either through visual pathological review [conventional pathology (CP)] or the deconvolution of molecular data. While CP provides a direct measurement, it demonstrates modest reproducibility and lacks standardisation.

Targeting the PREX2/RAC1/PI3Kβ Signaling Axis Confers Sensitivity to Clinically Relevant Therapeutic Approaches in Melanoma.

Metastatic melanoma remains a major clinical challenge. Large-scale genomic sequencing of melanoma has identified bona fide activating mutations in RAC1, which are associated with resistance to BRAF-targeting therapies. Targeting the RAC1-GTPase pathway, including the upstream activator PREX2 and the downstream effector PI3Kβ, could be a potential strategy for overcoming therapeutic resistance, limiting melanoma recurrence, and suppressing metastatic progression.

Dual gene set enrichment analysis (dualGSEA); an R function that enables more robust biological discovery and pre-clinical model alignment from transcriptomics data.

Gene set enrichment analysis (GSEA) tools can identify biological insights within gene expression-based studies. Although their statistical performance has been compared, the downstream biological implications that arise when choosing between the range of pairwise or single sample forms of GSEA methods remain understudied. We compare the statistical and biological results obtained from various pre-ranking methods/options for pairwise GSEA, followed by a stand-alone comparison of GSEA, single sample GSEA (ssGSEA) and gene set variation analysis (GSVA).

Diabetes prevention after gestational diabetes: challenges and opportunities.

Gestational diabetes mellitus (GDM) poses significant health concerns for women and their offspring, with implications that extend beyond pregnancy. While GDM often resolves postpartum, a diagnosis of GDM confers a greater risk of future type 2 diabetes (T2D) and other chronic illnesses. Furthermore, the intergenerational impact of GDM predisposes offspring to increased chronic disease risk.

Tumor-associated mesenchymal stromal cells modulate macrophage phagocytosis in stromal-rich colorectal cancer via PD-1 signaling.

CMS4 colorectal cancer (CRC), based on the consensus molecular subtype (CMS), stratifies patients with the poorest disease-free survival rates. It is characterized by a strong mesenchymal stromal cell (MSC) signature, wound healing-like inflammation and therapy resistance. We utilized 2D and 3D , and models to assess the impact of inflammation and stromal cells on immunosuppression in CMS4 CRC.

Stratification to Neoadjuvant Radiotherapy in Rectal Cancer by Regimen and Transcriptional Signatures.

Unlabelled: Response to neoadjuvant radiotherapy (RT) in rectal cancer has been associated with immune and stromal features that are captured by transcriptional signatures. However, how such associations perform across different chemoradiotherapy regimens and within individual consensus molecular subtypes (CMS) and how they affect survival remain unclear. In this study, gene expression and clinical data of pretreatment biopsies from nine cohorts of primary rectal tumors were combined (N = 826).

Identification and validation of a machine learning model of complete response to radiation in rectal cancer reveals immune infiltrate and TGFβ as key predictors.

Background: It is uncertain which biological features underpin the response of rectal cancer (RC) to radiotherapy. No biomarker is currently in clinical use to select patients for treatment modifications.

Methods: We identified two cohorts of patients (total N = 249) with RC treated with neoadjuvant radiotherapy (45Gy/25) plus fluoropyrimidine.

Exploring health professionals' knowledge, practices and attitudes regarding gestational diabetes: A cross-sectional Irish national survey.

Aim: Gestational diabetes confers short- and long-term risk of mother and offspring health complications. Healthcare professionals such as endocrinologists, diabetes nurses, dietitians, midwives and general practitioners provide gestational diabetes care. We sought to explore healthcare professionals' perspectives on gestational diabetes care during pregnancy and postpartum.

Image-based consensus molecular subtyping in rectal cancer biopsies and response to neoadjuvant chemoradiotherapy.

The development of deep learning (DL) models to predict the consensus molecular subtypes (CMS) from histopathology images (imCMS) is a promising and cost-effective strategy to support patient stratification. Here, we investigate whether imCMS calls generated from whole slide histopathology images (WSIs) of rectal cancer (RC) pre-treatment biopsies are associated with pathological complete response (pCR) to neoadjuvant long course chemoradiotherapy (LCRT) with single agent fluoropyrimidine. DL models were trained to classify WSIs of colorectal cancers stained with hematoxylin and eosin into one of the four CMS classes using a multi-centric dataset of resection and biopsy specimens (n = 1057 WSIs) with paired transcriptional data.

Pathway level subtyping identifies a slow-cycling biological phenotype associated with poor clinical outcomes in colorectal cancer.

Molecular stratification using gene-level transcriptional data has identified subtypes with distinctive genotypic and phenotypic traits, as exemplified by the consensus molecular subtypes (CMS) in colorectal cancer (CRC). Here, rather than gene-level data, we make use of gene ontology and biological activation state information for initial molecular class discovery. In doing so, we defined three pathway-derived subtypes (PDS) in CRC: PDS1 tumors, which are canonical/LGR5 stem-rich, highly proliferative and display good prognosis; PDS2 tumors, which are regenerative/ANXA1 stem-rich, with elevated stromal and immune tumor microenvironmental lineages; and PDS3 tumors, which represent a previously overlooked slow-cycling subset of tumors within CMS2 with reduced stem populations and increased differentiated lineages, particularly enterocytes and enteroendocrine cells, yet display the worst prognosis in locally advanced disease.

Molecular pathological classification of colorectal cancer-an update.

Colorectal cancer (CRC) has a broad range of molecular alterations with two major mechanisms of genomic instability (chromosomal instability and microsatellite instability) and has been subclassified into 4 consensus molecular subtypes (CMS) based on bulk RNA sequence data. Here, we update the molecular pathological classification of CRC with an overview of more recent bulk and single-cell RNA data analysis for development of transcriptional classifiers and risk stratification methods, taking into account the marked inter-tumoural and intra-tumoural heterogeneity of CRC. The importance of the stromal and immune components or tumour microenvironment (TME) to prognosis has emerged from these analyses.

Radiation-induced changes in gene expression in rectal cancer specimens.

Purpose: The standard-of-care for locally advanced rectal cancer is radiotherapy-based neoadjuvant therapy followed by surgical resection. This article reviews the evidence of molecular changes at the transcriptome level induced through radiotherapy in rectal cancer.

Methods: The PubMed search "(radiation OR radiotherapy) cancer (transcriptome OR "gene expression") rectal" was used.

Maternity Dietitians' Perspectives on Delivering Gestational Diabetes Care, and Postpartum Follow-Up in Ireland: A Qualitative Study.

Background: Medical nutrition therapy is recognized as the cornerstone to optimal glycemic management of gestational diabetes (GDM) during pregnancy and registered dietitian nutritionists (RDNs) are central to delivery of this, yet data are lacking on their views of the barriers and enablers to performing this role.

Objective: This qualitative study aimed to explore the perspectives of RDNs providing medical nutrition therapy to people with GDM across the Republic of Ireland.

Design: Focus groups and semistructured interviews were conducted with RDNs from maternity settings whose roles included providing dietetics services to people with GDM.

Poor Diagnostic Reproducibility in the Identification of Nonconventional Dysplasia in Colitis Impacts the Application of Histologic Stratification Tools.

Due to their increased cancer risk, patients with longstanding inflammatory bowel disease are offered endoscopic surveillance with concomitant histopathologic assessments, aimed at identifying dysplasia as a precursor lesion of colitis-associated colorectal cancer. However, this strategy is beset with difficulties and limitations. Recently, a novel classification criterion for colitis-associated low-grade dysplasia has been proposed, and an association between nonconventional dysplasia and progression was reported, suggesting the possibility of histology-based stratification of patients with colitis-associated lesions.

Combined quantitative lipidomics and back-propagation neural network approach to discriminate the breed and part source of lamb.

The study successfully utilized an analytical approach that combined quantitative lipidomics with back-propagation neural networks to identify breed and part source of lamb using small-scale samples. 1230 molecules across 29 lipid classes were identified in longissimus dorsi and knuckle meat of both Tan sheep and Bahan crossbreed sheep. Applying multivariate statistical methods, 12 and 7 lipid molecules were identified as potential markers for breed and part identification, respectively.

Pre-emptive TIPS in high-risk acute variceal bleeding. An updated and revised individual patient data meta-analysis.

Background And Aims: A previous individual patient data meta-analysis (IPD-MA) showed that compared with drugs+endoscopy, the placement of transjugular portosystemic shunt within 72 hours of admission (pre-emptive transjugular intrahepatic portosystemic shunt: p-TIPS) increases the survival of high-risk patients (Child-Pugh B+ active bleeding and Child-Pugh C<14 points) with cirrhosis and acute variceal bleeding. However, the previous IPD-MA was not a two-stage meta-analysis, did not consider the potential risk of selection bias of observational studies, and did not include the most recent randomized clinical trial. We performed an updated and revised IPD-MA to reassess the efficacy of p-TIPS, addressing all previous issues.