A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial.

Background: Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn's disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing outcomes in patients randomised to either top-down (ie, early combined immunosuppression with infliximab and immunomodulator) or accelerated step-up (conventional) treatment strategies.

Methods: PROFILE (PRedicting Outcomes For Crohn's disease using a moLecular biomarker) was a multicentre, open-label, biomarker-stratified, randomised controlled trial that enrolled adults with newly diagnosed active Crohn's disease (Harvey-Bradshaw Index ≥7, either elevated C-reactive protein or faecal calprotectin or both, and endoscopic evidence of active inflammation).

Active surveillance of adverse events following COVID-19 vaccines in a tertiary care hospital.

Background: Vaccination is a safe and effective way to prevent disease and save lives, but it may also produce some undesirable adverse events (AEs)which may affect healthy individuals. Therefore, the monitoring of AE following immunization (AEFIs) is necessary. The objective of this study was to assess the AEs following COVID-19 vaccinations in a tertiary care hospital.

Automatic severity grade classification of diabetic retinopathy using deformable ladder Bi attention U-net and deep adaptive CNN.

Long-term exposure to diabetes mellitus leads to the formation of diabetic retinopathy (DR), which can cause vision loss in working-age adults. Early stage diagnosis of DR is highly essential for preventing vision loss and preserving vision in people with diabetes. The motivation behind the severity grade classification of DR is to develop an automated system that can assist ophthalmologists and healthcare professionals in the diagnosis and management of DR.

Epstein-Barr Virus-Positive Mucocutaneous Ulcers Complicate Colitis Caused by Immune Checkpoint Regulator Therapy and Associate With Colon Perforation.

Background & Aims: Cancer therapy with immune checkpoint inhibitors can cause colitis and colon perforation. We investigated whether infection with Epstein Barr virus (EBV) associates with development and severity of colitis in patients receiving immune checkpoint inhibitor therapies.

Methods: We performed a retrospective analysis of fixed colon tissues from 16 patients (12 men, 4 women, median age, 69.

The Ussing chamber system for measuring intestinal permeability in health and disease.

Background: The relationship between intestinal epithelial integrity and the development of intestinal disease is of increasing interest. A reduction in mucosal integrity has been associated with ulcerative colitis, Crohn's disease and potentially could have links with colorectal cancer development. The Ussing chamber system can be utilised as a valuable tool for measuring gut integrity.

Improving in-silico normalization using read weights.

Specialized de novo assemblers for diverse datatypes have been developed and are in widespread use for the analyses of single-cell genomics, metagenomics and RNA-seq data. However, assembly of large sequencing datasets produced by modern technologies is challenging and computationally intensive. In-silico read normalization has been suggested as a computational strategy to reduce redundancy in read datasets, which leads to significant speedups and memory savings of assembly pipelines.

In silico read normalization using set multi-cover optimization.

Motivation: De Bruijn graphs are a common assembly data structure for sequencing datasets. But with the advances in sequencing technologies, assembling high coverage datasets has become a computational challenge. Read normalization, which removes redundancy in datasets, is widely applied to reduce resource requirements.

Informed kmer selection for de novo transcriptome assembly.

Motivation: De novo transcriptome assembly is an integral part for many RNA-seq workflows. Common applications include sequencing of non-model organisms, cancer or meta transcriptomes. Most de novo transcriptome assemblers use the de Bruijn graph (DBG) as the underlying data structure.

Two sets of RNAi components are required for heterochromatin formation in trans triggered by truncated transgenes.

Across kingdoms, RNA interference (RNAi) has been shown to control gene expression at the transcriptional- or the post-transcriptional level. Here, we describe a mechanism which involves both aspects: truncated transgenes, which fail to produce intact mRNA, induce siRNA accumulation and silencing of homologous loci in trans in the ciliate Paramecium We show that silencing is achieved by co-transcriptional silencing, associated with repressive histone marks at the endogenous gene. This is accompanied by secondary siRNA accumulation, strictly limited to the open reading frame of the remote locus.

Zinc in denture adhesive: a rare cause of copper deficiency in a patient on home parenteral nutrition.

A 65-year-old woman with Crohn's disease, who had been on home parenteral nutrition for many years, presented with perioral paraesthesia and a burning sensation in the mouth. Initial blood tests including serum ferritin, vitamin B12 and folate, were normal apart from mild pancytopaenia. Serum copper was low, in spite of receiving regular copper in her parenteral feeds.

Development and validation of the Gastrointestinal Endoscopy Satisfaction Questionnaire (GESQ).

Background And Study Aims: Patient satisfaction is a key indicator of the quality of gastrointestinal (GI) endoscopy. The aim of this study was to develop and validate a specific patient satisfaction questionnaire for patients undergoing GI endoscopy--the Gastrointestinal Endoscopy Satisfaction Questionnaire (GESQ).

Patients And Methods: We developed and validated the GESQ within the context of a national multi-institution nurse endoscopy trial, based in secondary care, in three stages: (1) item generation with a panel of patients and professionals following a detailed literature review to identify the most relevant items from existing scales; (2) development and piloting of a draft questionnaire on a sample of patients referred for GI endoscopy; and (3) testing of the questionnaire within a large multicenter pragmatic randomized trial.

Successful development and testing of a Method for Aggregating The Reporting of Interventions in Complex Studies (MATRICS).

Objectives: To develop a tool for the accurate reporting and aggregation of findings from each of the multiple methods used in a complex evaluation in an unbiased way.

Study Design And Setting: We developed a Method for Aggregating The Reporting of Interventions in Complex Studies (MATRICS) within a gastroenterology study [Evaluating New Innovations in (the delivery and organisation of) Gastrointestinal (GI) endoscopy services by the NHS Modernisation Agency (ENIGMA)]. We subsequently tested it on a different gastroenterology trial [Multi-Institutional Nurse Endoscopy Trial (MINuET)].

Psychometric development of the Gastrointestinal Symptom Rating Questionnaire (GSRQ) demonstrated good validity.

Objectives: To develop and validate a gastrointestinal (GI) symptom rating questionnaire for patients with luminal GI symptoms including where no diagnosis has been made.

Study Design And Setting: We developed and validated the Gastrointestinal Symptom Rating Questionnaire (GSRQ) in three stages: (1) item generation to identify the relevant items for scale inclusion; (2) development and piloting on patients with a known GI disorder; and (3) testing in a sample of trial patients. We examined the underlying dimensions of the scale, internal consistency, validity, reproducibility, and responsiveness.

SHARP: genome-scale identification of gene-protein-reaction associations in cyanobacteria.

Genome scale metabolic model provides an overview of an organism's metabolic capability. These genome-specific metabolic reconstructions are based on identification of gene to protein to reaction (GPR) associations and, in turn, on homology with annotated genes from other organisms. Cyanobacteria are photosynthetic prokaryotes which have diverged appreciably from their nonphotosynthetic counterparts.

Halobacterium sp. SP1(1) as a starter culture for accelerating fish sauce fermentation.

Aims: Application of Halobacterium sp. SP1(1) for the acceleration of fish sauce fermentation.

Methods And Results: Traditional fish sauce fermentation was mimicked using Halobacterium sp.

Cost effectiveness of nurse delivered endoscopy: findings from randomised multi-institution nurse endoscopy trial (MINuET).

Objective: To compare the cost effectiveness of nurses and doctors in performing upper gastrointestinal endoscopy and flexible sigmoidoscopy.

Design: As part of a pragmatic randomised trial, the economic analysis calculated incremental cost effectiveness ratios, and generated cost effectiveness acceptability curves to address uncertainty.

Setting: 23 hospitals in the United Kingdom.

Effectiveness of nurse delivered endoscopy: findings from randomised multi-institution nurse endoscopy trial (MINuET).

Objective: To compare the clinical effectiveness of doctors and nurses in undertaking upper and lower gastrointestinal endoscopy.

Design: Pragmatic trial with Zelen's randomisation before consent to minimise distortion of existing practice.

Setting: 23 hospitals in the United Kingdom.

Organic solvent tolerance of Halobacterium sp. SP1(1) and its extracellular protease.

Halophilic archaea belonging to three different genera- Halobacterium, Haloarcula and Haloferax, were isolated from Kandla salt pans. The isolates had an optimum requirement of 25% NaCl for growth. Increase in organic solvent tolerance of isolates was observed at higher NaCl concentrations.

What are the clinical outcome and cost-effectiveness of endoscopy undertaken by nurses when compared with doctors? A Multi-Institution Nurse Endoscopy Trial (MINuET).

Objectives: To compare the clinical outcome and cost-effectiveness of doctors and nurses undertaking upper and lower gastrointestinal endoscopy.

Design: The study was a pragmatic randomised controlled trial. Zelen's randomisation before consent was used to minimise distortion of existing practice in the participating sites.

Review article: how and when to use ciclosporin in ulcerative colitis.

Although colectomy for ulcerative colitis is curative, long-term quality of life is reduced. Intravenous ciclosporin 4 mg/kg/day has significant toxicity. There is now evidence that low-dose ciclosporin (2 mg/kg daily by intravenous infusion, or 5-6 mg/kg daily in a twice daily oral dosage) has an acceptable safety profile, even when used in combination with corticosteroids.

GOAL: a simplified mental test for emergency medical admissions.

Background: Several scoring systems are used in screening for cognitive impairment, but none are suited to the busy medical assessment environment.

Aim: To construct, validate and assess the reliability of a simple scale (Gwent Orientation and Awareness Listing, GOAL) for this purpose, and to examine its application in consecutive emergency admissions in two general hospitals.

Design: Prospective cohort studies.

Regression of primary high-grade gastric B-cell lymphoma following Helicobacter pylori eradication.

The causative association between Helicobacter pylori and gastric mucosal inflammation is well established. The inflammatory process leads to the acquisition of mucosa-associated lymphoid tissue (MALT) by the stomach. Evidence links H.