Discovery of Highly Selective Inhibitors of Microtubule-Associated Serine/Threonine Kinase-like (MASTL).

By virtue of its role in cellular proliferation, microtubule-associated serine/threonine kinase-like (MASTL) represents a novel target and a first-in-class (FIC) opportunity to provide a new impactful therapeutic agent to oncology patients. Herein, we describe a hit-to-lead optimization effort that resulted in the delivery of two highly selective MASTL inhibitors. Key strategies leveraged to enable this work included structure-based drug design (SBDD), analysis of lipophilic efficiency (LipE) and novel synthesis.

Gas Chromatography-Sensor System Aids Diagnosis of Inflammatory Bowel Disease, and Separates Crohn's from Ulcerative Colitis, in Children.

The diagnosis of inflammatory bowel disease (IBD) in children and the need to distinguish between subtypes (Crohn's disease (CD) and ulcerative colitis (UC)) requires lengthy investigative and invasive procedures. Non-invasive, rapid, and cost-effective tests to support these diagnoses are needed. Faecal volatile organic compounds (VOCs) are distinctive in IBD.

Soft drug inhibitors for the epigenetic targets lysine-specific demethylase 1 and histone deacetylases.

Epigenetic modulators such as lysine-specific demethylase 1 (LSD1) and histone deacetylases (HDACs) are drug targets for cancer, neuropsychiatric disease, or inflammation, but inhibitors of these enzymes exhibit considerable side effects. For a potential local treatment with reduced systemic toxicity, we present here soft drug candidates as new LSD1 and HDAC inhibitors. A soft drug is a compound that is degraded in vivo to less active metabolites after having achieved its therapeutic function.

Onset of spin entanglement in doped carbon nanotubes studied by EPR.

Nanoscale semiconductors with isolated spin impurities have been touted as promising materials for their potential use at the intersection of quantum, spin, and information technologies. Electron paramagnetic resonance (EPR) studies of spins in semiconducting carbon nanotubes have overwhelmingly focused on spins more strongly localized by sp3-type lattice defects. However, the creation of such impurities is irreversible and requires specific reactions to generate them.

Swallowed topical steroid therapy for eosinophilic oesophagitis in children: practical, evidence-based guidance by the BSPGHAN Eosinophilic Oesophagitis Working Group.

Objective: To develop evidence-based guidance for topical steroid use in paediatric eosinophilic oesophagitis (pEoE) in the UK for both induction and maintenance treatment.

Methods: A systematic literature review using Cochrane guidance was carried out by the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) Eosinophilic Oesophagitis (EoE) Working Group (WG) and research leads to determine the evidence base for preparation, dosing and duration of use of swallowed topical steroid (STS) formulations in EoE. Seven themes relating to pEoE were reviewed by the WG, alongside the Cochrane review this formed the evidence base for consensus recommendations for pEoE in the UK.

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis.

Introduction: Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs.

Variation in access and prescription of vedolizumab and ustekinumab in paediatric patients with inflammatory bowel disease: a UK-wide study.

Background: Therapeutic options for paediatric inflammatory bowel disease (IBD) are limited, especially for younger children. Unlike in adults, vedolizumab and ustekinumab are not licensed for paediatric use in the UK. We aimed to understand the real-world access to, and use of, these therapies in the paediatric population.

Eosinophilic oesophagitis: improving diagnosis and therapy - reducing the burden of repeated endoscopy.

Eosinophilic oesophagitis is now being diagnosed more often, although there continues to be a significant delay in the recognition of the condition in primary care, and among patients presenting with food bolus obstruction to other specialities like Ears, Nose and Throat and Accident & Emergency. The diagnosis requires endoscopy and biopsy, with six biopsies taken from at least two different areas of the oesophagus. The diagnostic threshold is > 15 eosinophils/high power field or 0.

British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults.

Background: Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE.

Methods: The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines.

International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature.

Background & Aims: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature.

Methods: This consensus process utilized Delphi methodology.

Management of eosinophilic esophagitis associated food impaction in Europe and the United States.

Eosinophilic esophagitis (EoE) is the most common cause of esophageal food impaction (EFI). Approaches to management of EFI due to EoE have not been well characterized. We conducted a web-based survey to understand approaches to management of EFI due to EoE among endoscopists.

Safety, Tolerability, and Pharmacokinetics of Oral Ferric Maltol in Children With Iron Deficiency: Phase 1 Study.

Unlabelled: Iron deficiency is common in children and can have negative effects on behavior and function. Standard oral ferrous iron replacement is poorly absorbed and can cause treatment-limiting gastrointestinal adverse events (AEs). Ferric maltol is formulated to improve gastrointestinal absorption and tolerability versus oral ferrous compounds.

Highly conducting Wurster-type twisted covalent organic frameworks.

Covalent organic frameworks (COFs) define a versatile structural paradigm combining attractive properties such as crystallinity, porosity, and chemical and structural modularity which are valuable for various applications. For the incorporation of COFs into optoelectronic devices, efficient charge carrier transport and intrinsic conductivity are often essential. Here, we report the synthesis of two imine-linked two-dimensional COFs, WTA and WBDT, featuring a redox-active Wurster-type motif based on the twisted tetragonal ,,','-tetraphenyl-1,4-phenylenediamine node.

The role of RST1 and RIPR proteins in plant RNA quality control systems.

To keep mRNA homeostasis, the RNA degradation, quality control and silencing systems should act in balance in plants. Degradation of normal mRNA starts with deadenylation, then deadenylated transcripts are degraded by the SKI-exosome 3'-5' and/or XRN4 5'-3' exonucleases. RNA quality control systems identify and decay different aberrant transcripts.

Adaptations to the current ECCO/ESPGHAN guidelines on the management of paediatric acute severe colitis in the context of the COVID-19 pandemic: a RAND appropriateness panel.

Objective: Paediatric acute severe colitis (ASC) management during the novel SARS-CoV-2/COVID-19 pandemic is challenging due to reliance on immunosuppression and the potential for surgery. We aimed to provide COVID-19-specific guidance using the European Crohn's and Colitis Organisation/European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for comparison.

Design: We convened a RAND appropriateness panel comprising 14 paediatric gastroenterologists and paediatric experts in surgery, rheumatology, respiratory and infectious diseases.

The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) Index: A Prognostic Tool for Children.

Background And Aims: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC.