Spatially Resolved Tumor Ecosystems and Cell States in Gastric Adenocarcinoma Progression and Evolution.

Gastric cancer (GC) is a major cause of global cancer mortality with high levels of heterogeneity. To explore geospatial interactions in tumor ecosystems, we integrated 2,138 spatial transcriptomic regions-of-interest (ROIs) with 152,423 single-cell expression profiles across 226 GC samples from 121 patients. We observed pervasive expression-based intratumor heterogeneity, recapitulating tumor progression through spatially localized and functionally ordered subgroups associated with specific immune microenvironments, checkpoint profiles, and genetic drivers such as SOX9.

IQGAP3 signalling mediates intratumoral functional heterogeneity to enhance malignant growth.

Background: The elevation of IQGAP3 expression in diverse cancers indicates a key role for IQGAP3 in carcinogenesis. Although IQGAP3 was established as a proliferating stomach stem cell factor and a regulator of the RAS-ERK pathway, how it drives cancer growth remains unclear.

Objective: We define the function of IQGAP3 in gastric cancer (GC) development and progression.

Assessing the Utility, Impact, and Adoption Challenges of an Artificial Intelligence-Enabled Prescription Advisory Tool for Type 2 Diabetes Management: Qualitative Study.

Background: The clinical management of type 2 diabetes mellitus (T2DM) presents a significant challenge due to the constantly evolving clinical practice guidelines and growing array of drug classes available. Evidence suggests that artificial intelligence (AI)-enabled clinical decision support systems (CDSSs) have proven to be effective in assisting clinicians with informed decision-making. Despite the merits of AI-driven CDSSs, a significant research gap exists concerning the early-stage implementation and adoption of AI-enabled CDSSs in T2DM management.

CEACAM5 and TROP2 define metaplastic and dysplastic transitions in human antral gastric precancerous lesions and tumors.

Background: Mucosal gastric atrophy and intestinal metaplasia (IM) increase the risk for the development of gastric cancer (GC) as they represent a field for development of dysplasia and intestinal-type gastric adenocarcinoma.

Methods: We have investigated the expression of two dysplasia markers, CEACAM5 and TROP2, in human antral IM and gastric tumors to assess their potential as molecular markers.

Results: In the normal antral mucosa, weak CEACAM5 and TROP2 expression was only observed in the foveolar epithelium, while inflamed antrum exhibited increased expression of both markers.

Spatiotemporal genomic profiling of intestinal metaplasia reveals clonal dynamics of gastric cancer progression.

Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. Analyzing 1,256 gastric samples (1,152 IMs) across 692 subjects from a prospective 10-year study, we identify 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9). Single-cell and spatial profiles highlight changes in tissue ecology and IM lineage heterogeneity, including an intestinal stem-cell dominant cellular compartment linked to early malignancy.

A real-life comparison of hypoglycaemia symptomatology between insulin-treated type 2 diabetes participants with and without impaired awareness of hypoglycaemia.

Aims: We aim to compare and correlate Gold and Clarke questionnaire scores with hypoglycaemic symptomatic responses between insulin-treated type 2 diabetes participants with and without IAH in a real-life study.

Methods: Insulin-treated type 2 diabetes participants attending an outpatient diabetes clinic in Singapore were asked to complete the Gold and Clarke questionnaires, record capillary blood glucose (CBG) and hypoglycaemic symptoms for 4 weeks.

Results: Data were collected from 153 participants (M:F = 98:55) with mean age 61.

RUNX3 inactivates oncogenic MYC through disruption of MYC/MAX complex and subsequent recruitment of GSK3β-FBXW7 cascade.

MYC is one of the most commonly dysregulated proto-oncogenes in cancer. MYC promotes cancer initiation and maintenance by regulating multiple biological processes, such as proliferation and stem cell function. Here, we show that developmental regulator RUNX3 targets MYC protein for rapid degradation through the glycogen synthase kinase-3 beta-F-box/WD repeat-containing protein 7 (GSK3β-FBXW7) proteolytic pathway.

Telemonitoring With a Connected Glucose Meter Improves Glycemia Among People With Insulin-Treated Type 2 Diabetes.

Background: Delayed initiation and inadequate titration remain critical challenges to optimizing insulin therapy in type 2 diabetes (T2D). We aimed to study whether hemoglobin A1c (HbA1c) can be lowered in people with insulin-treated T2D using telemonitoring.

Methods: This single-center study recruited adults with greater than or equal to six months of diabetes, greater than or equal to three months of insulin therapy, HbA1c ≥8.

Evaluation of Care Outcomes of Patients Receiving Hyperkalemia Treatment With Insulin in Acute Care Tertiary Hospital Emergency Department.

Introduction: Treatment of hyperkalemia using intravenous insulin can result in severe hypoglycemia, but regular blood glucose monitoring is not standardized. This study aimed to (i) explore the demographics of adult patients receiving hyperkalemia treatment and (ii) identify the incidence rate of hypoglycemia and associated demographic or clinical characteristics.

Methods: A descriptive design with prospective data collection was used.

Academy of Medicine, Singapore clinical guideline on endoscopic surveillance and management of gastric premalignant lesions.

Gastric cancer (GC) has a good prognosis, if detected at an early stage. The intestinal subtype of GC follows a stepwise progression to carcinoma, which is treatable with early detection and intervention using high-quality endoscopy. Premalignant lesions and gastric epithelial polyps are commonly encountered in clinical practice.

Regulatory enhancer profiling of mesenchymal-type gastric cancer reveals subtype-specific epigenomic landscapes and targetable vulnerabilities.

Objective: Gastric cancer (GC) comprises multiple molecular subtypes. Recent studies have highlighted mesenchymal-subtype GC (Mes-GC) as a clinically aggressive subtype with few treatment options. Combining multiple studies, we derived and applied a consensus Mes-GC classifier to define the Mes-GC enhancer landscape revealing disease vulnerabilities.

High incidence of undetected low sensor glucose events among elderly patients with type 2 diabetes more than a decade on after the ACCORD study.

Objective: Hypoglycaemia leads to significant morbidity and impacts negatively on quality-of-life, especially in elderly people with increased frailty. The aims of this study were to determine the prevalence of low interstitial fluid glucose (IFG) in patients with tightly controlled type 2 diabetes (T2D), and to evaluate whether there were differences in burden of low IFG between sulphonylurea and insulin treated groups.

Methods: A Freestyle Libre-Pro sensor was used for sampling of the IFG continuously.

ISM1 protects lung homeostasis via cell-surface GRP78-mediated alveolar macrophage apoptosis.

Alveolar macrophages (AMs) are critical for lung immune defense and homeostasis. They are orchestrators of chronic obstructive pulmonary disease (COPD), with their number significantly increased and functions altered in COPD. However, it is unclear how AM number and function are controlled in a healthy lung and if changes in AMs without environmental assault are sufficient to trigger lung inflammation and COPD.

Single-Cell Atlas of Lineage States, Tumor Microenvironment, and Subtype-Specific Expression Programs in Gastric Cancer.

Unlabelled: Gastric cancer heterogeneity represents a barrier to disease management. We generated a comprehensive single-cell atlas of gastric cancer (>200,000 cells) comprising 48 samples from 31 patients across clinical stages and histologic subtypes. We identified 34 distinct cell-lineage states including novel rare cell populations.

Induction of Gastric Cancer by Successive Oncogenic Activation in the Corpus.

Background & Aims: Metaplasia and dysplasia in the corpus are reportedly derived from de-differentiation of chief cells. However, the cellular origin of metaplasia and cancer remained uncertain. Therefore, we investigated whether pepsinogen C (PGC) transcript-expressing cells represent the cellular origin of metaplasia and cancer using a novel Pgc-specific CreERT2 recombinase mouse model.

Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation.

Background: CIMP (CpG island methylator phenotype) is an epigenetic molecular subtype, observed in multiple malignancies and associated with the epigenetic silencing of tumor suppressors. Currently, for most cancers including gastric cancer (GC), mechanisms underlying CIMP remain poorly understood. We sought to discover molecular contributors to CIMP in GC, by performing global DNA methylation, gene expression, and proteomics profiling across 14 gastric cell lines, followed by similar integrative analysis in 50 GC cell lines and 467 primary GCs.

Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP).

Objective: To investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC.

Methods: A prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5.

WBP2 promotes gastric cancer cell migration via novel targeting of LATS2 kinase in the Hippo tumor suppressor pathway.

Dysregulation of signaling pathways is responsible for many human diseases. The lack of understanding of the molecular etiology of gastric cancer (GC) poses a substantial challenge to the development of effective cancer therapy. To better understand the molecular mechanisms underlying the pathogenesis of GC, which will facilitate the identification and development of effective therapeutic approaches to improve patient outcomes, mass spectrometry-based phosphoproteomics analysis was performed to map the global molecular changes in GC.

Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair.

Objective: Tissue stem cells are central regulators of organ homoeostasis. We looked for a protein that is exclusively expressed and functionally involved in stem cell activity in rapidly proliferating isthmus stem cells in the stomach corpus.

Design: We uncovered the specific expression of Iqgap3 in proliferating isthmus stem cells through immunofluorescence and in situ hybridisation.

An LCM-based genomic analysis of SPEM, Gastric Cancer and Pyloric Gland Adenoma in an Asian cohort.

Spasmolytic polypeptide-expressing metaplasia (SPEM) and pyloric gland adenoma (PGA) in the stomach are metaplastic and neoplastic lesions, respectively, in which gastric body glands are replaced by pyloric glands. The aim of this study was to evaluate the genomic profile of SPEM and compare it with intestinal-type gastric cancer (GC) and PGA. Thirteen gastrectomies showing PGA with or without dysplasia, GC and SPEM were retrospectively selected.

AQP5 enriches for stem cells and cancer origins in the distal stomach.

LGR5 marks resident adult epithelial stem cells at the gland base in the mouse pyloric stomach, but the identity of the equivalent human stem cell population remains unknown owing to a lack of surface markers that facilitate its prospective isolation and validation. In mouse models of intestinal cancer, LGR5 intestinal stem cells are major sources of cancer following hyperactivation of the WNT pathway. However, the contribution of pyloric LGR5 stem cells to gastric cancer following dysregulation of the WNT pathway-a frequent event in gastric cancer in humans-is unknown.

DNA damage signalling as an anti-cancer barrier in gastric intestinal metaplasia.

Objective: Intestinal metaplasia (IM) is a premalignant stage that poses a greater risk for subsequent gastric cancer (GC). However, factors regulating IM to GC progression remain unclear. Previously, activated DNA damage response (DDR) signalling factors were shown to engage tumour-suppressive networks in premalignant lesions.

Clustering of lifestyle risk behaviours and its determinants among school-going adolescents in a middle-income country: a cross-sectional study.

Background: Lifestyle risk behaviours such as smoking, alcohol consumption, physical inactivity, sedentary behaviour and low fruit/vegetable intake have been identified as the major causes of chronic diseases. Such behaviours are usually instigated in adolescence and tend to persist into adulthood. Studies on the clustering of lifestyle risk behaviours among adolescents are scarce, particularly in developing countries.