EmbedGEM: a framework to evaluate the utility of embeddings for genetic discovery.

Summary: Machine learning-derived embeddings are a compressed representation of high content data modalities. Embeddings can capture detailed information about disease states and have been qualitatively shown to be useful in genetic discovery. Despite their promise, embeddings have a major limitation: it is unclear if genetic variants associated with embeddings are relevant to the disease or trait of interest.

The role of mesenchymal cells in cholangiocarcinoma.

The tumour microenvironment (TME) significantly influences tumour formation and progression through dynamic interactions. Cholangiocarcinoma (CCA), a highly desmoplastic tumour, lacks early diagnostic biomarkers and has limited effective treatments owing to incomplete understanding of its molecular pathogenesis. Investigating the role of the TME in CCA progression could lead to better therapies.

Impact of Skin Decontamination Wipe Solutions on the Percutaneous Absorption of Polycyclic Aromatic Hydrocarbons.

Firefighter occupational exposures were categorized as a class 1 (known) carcinogen by the International Agency for Research on Cancer in 2022. As a result, firefighters have become heavily focused on identifying effective and easy to implement decontamination strategies to reduce their chemical exposures. Skin decontamination using wipes post-exposure is one decontamination strategy that every firefighter has available to them.

Supplementation with Citrus Low-Methoxy Pectin Reduces Levels of Inflammation and Anxiety in Healthy Volunteers: A Pilot Controlled Dietary Intervention Study.

Although low-methoxy (LM) pectin (polysaccharides extracted from citrus peels) can reduce inflammation by binding to and inhibiting the TLR-2 pathway in animal models and in vitro studies, the anti-inflammatory effects of LM pectin in humans and mood have not been explored to date. The purpose of this study is to assess the role of dietary supplementation with LM pectin in healthy volunteers on inflammatory markers and on mood, specifically anxiety and depression. We carried out a 4-week dietary intervention with LM citrus pectin on healthy volunteers (N = 14, age 40 ± 16 y, BMI 24.

Analysis of urinary volatile organic compounds for prostate cancer diagnosis: A systematic review.

Context: Prostate-specific antigen is non-specific for prostate cancer. This is improved by multiparametric MRI but a significant amount of indolent prostate cancer is detected by the current MRI pathway and data is emerging that clinically significant cancers maybe missed using a standard PSA threshold. Volatile organic compound (VOC) analysis may offer novel biomarkers for prostate cancer and clinically significant disease.

Percutaneous Absorption of Fireground Contaminants: Naphthalene, Phenanthrene, and Benzo[a]pyrene in Porcine Skin in an Artificial Sweat Vehicle.

Firefighters face significant risks of exposure to toxic chemicals, such as polycyclic aromatic hydrocarbons (PAHs), during fire suppression activities. PAHs have been found in the air, on the gear and equipment, and in biological samples such as the skin, breath, urine, and blood of firefighters after fire response. However, the extent to which exposure occurs via inhalation, dermal absorption, or ingestion is unclear.

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.

Assessing 'response' to the low-FODMAP diet in irritable bowel syndrome: Should we be reporting harder primary endpoints?

Background & Aims: The low-FODMAP diet (LFD) has become almost synonymous with IBS care, yet the challenges associated with this rigorous therapeutic approach are often underacknowledged. Despite positive outcomes in RCTs, comparator groups frequently exhibit substantial response rates, raising questions about the definition of 'response'. Whilst the assessment of response in drug trials has evolved to utilize the more stringent FDA/EMA primary clinical endpoints, trials of the LFD have not yet followed.

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).

Shoring up the base: the development and regulation of cortical sclerenchyma in grass nodal roots.

Plants depend on the combined action of a shoot-root-soil system to maintain their anchorage to the soil. Mechanical failure of any component of this system results in lodging, a permanent and irreversible inability to maintain vertical orientation. Models of anchorage in grass crops identify the compressive strength of roots near the soil surface as key determinant of resistance to lodging.

A novel Monash Pouch diet in patients with an ileoanal pouch is tolerable and has favorable metabolic luminal effects.

Aims: To evaluate a whole-food diet strategy (the Monash Pouch diet [MPD]) designed based on the interacting roles dietary factors play with pouch health. Specifically, its tolerability and acceptability, whether it achieved its dietary and metabolic goals, and the effects on symptoms and inflammation were examined.

Methods: In a 6-week open-label trial, patients with ileoanal pouches educated on the MPD were assessed regarding diet tolerability and acceptance, food intake (7-day food diaries), pouch-related symptoms (clinical pouchitis disease activity index), and, in 24-h fecal samples, calprotectin, fermentative biomarkers, and volatile organic compounds (VOC).

Application of a 3D hydrogel-based model to replace use of animals for passaging patient-derived xenografts.

Purpose: This 3D in vitro cancer model for propagation of patient-derived cells, using a synthetic self-assembling peptide gel, allows the formation of a fully characterised, tailorable tumour microenvironment. Unlike many existing 3D cancer models, the peptide gel is inert, apart from molecules and motifs deliberately added or produced by cells within the model.

Methods: Breast cancer patient-derived xenografts (PDXs) were disaggregated and embedded in a peptide hydrogel.

CTCF is essential for proper mitotic spindle structure and anaphase segregation.

Mitosis is an essential process in which the duplicated genome is segregated equally into two daughter cells. CTCF has been reported to be present in mitosis and has a role in localizing CENP-E, but its importance for mitotic fidelity remains to be determined. To evaluate the importance of CTCF in mitosis, we tracked mitotic behaviors in wild-type and two different CTCF CRISPR-based genetic knockdowns.

The role of iron in the pathogenesis of endometriosis: a systematic review.

Study Question: What is the role of iron in the pathophysiology of endometriosis?

Summary Answer: Iron excess is demonstrated wherever endometriotic tissues are found and is associated with oxidative stress, an inflammatory micro-environment, and cell damage; the iron-mediated oxidative stress is independently linked to subfertility, symptom severity, and malignant transformation.

What Is Known Already: Iron is found in excess in endometriotic tissues, and multiple mechanisms have been studied and posited to explain this. It is clear that iron excess plays a vital role in promoting oxidative stress and cell damage.

Faecal and urine metabolites, but not gut microbiota, may predict response to low FODMAP diet in irritable bowel syndrome.

Background: The low FODMAP diet (LFD) leads to clinical response in 50%-80% of patients with irritable bowel syndrome (IBS). It is unclear why only some patients respond.

Aims: To determine if differences in baseline faecal microbiota or faecal and urine metabolite profiles may separate clinical responders to the diet from non-responders allowing predictive algorithms to be proposed.

CTCF is essential for proper mitotic spindle structure and anaphase segregation.

Mitosis is an essential process in which the duplicated genome is segregated equally into two daughter cells. CTCF has been reported to be present in mitosis but its importance for mitotic fidelity remains to be determined. To evaluate the importance of CTCF in mitosis, we tracked mitotic behaviors in wild type and two different CTCF CRISPR-based genetic knockdowns.

GC-MS Techniques Investigating Potential Biomarkers of Dying in the Last Weeks with Lung Cancer.

Predicting when a patient with advanced cancer is dying is a challenge and currently no prognostic test is available. We hypothesised that a dying process from cancer is associated with metabolic changes and specifically with changes in volatile organic compounds (VOCs). We analysed urine from patients with lung cancer in the last weeks of life by headspace gas chromatography mass spectrometry.

Mechanisms affecting the gut of preterm infants in enteral feeding trials: a nested cohort within a randomised controlled trial of lactoferrin.

Objective: To determine the impact of supplemental bovine lactoferrin on the gut microbiome and metabolome of preterm infants.

Design: Cohort study nested within a randomised controlled trial (RCT). Infants across different trial arms were matched on several clinical variables.

Patient preferences and current practice for adults with steroid-resistant ulcerative colitis: POPSTER mixed-methods study.

Background: Corticosteroids are a mainstay of the treatment of moderately severe relapses of ulcerative colitis, yet almost 50% of patients do not respond fully to these and risk prolonged steroid use and side effects. There is a lack of clarity about the definitions of steroid resistance, the optimum choice of treatment, and patient and health-care professional treatment preferences.

Objectives: The overall aim of this research was to understand how steroid-resistant ulcerative colitis is managed in adult secondary care and how current practice compares with patient and health-care professional preferences.

The impact of almonds and almond processing on gastrointestinal physiology, luminal microbiology, and gastrointestinal symptoms: a randomized controlled trial and mastication study.

Background: Almonds contain lipid, fiber, and polyphenols and possess physicochemical properties that affect nutrient bioaccessibility, which are hypothesized to affect gut physiology and microbiota.

Objectives: To investigate the impact of whole almonds and ground almonds (almond flour) on fecal bifidobacteria (primary outcome), gut microbiota composition, and gut transit time.

Methods: Healthy adults (n = 87) participated in a parallel, 3-arm randomized controlled trial.

deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa.

The alternative (noncanonical) nuclear factor-κB (NF-κB) signaling pathway predominantly regulates the function of the p52/RelB heterodimer. Germline 2 deficiency in mice leads to loss of p100/p52 protein and offers protection against a variety of gastrointestinal conditions, including azoxymethane/dextran sulfate sodium (DSS)-induced colitis-associated cancer and lipopolysaccharide (LPS)-induced small intestinal epithelial apoptosis. However, the common underlying protective mechanisms have not yet been fully elucidated.

Efficacy and Safety of Elective Switching from Intravenous to Subcutaneous Infliximab [CT-P13]: A Multicentre Cohort Study.

Background: Intravenous [IV] infliximab is a well-established therapy for inflammatory bowel diseases [IBD] patients. A subcutaneous [SC] formulation of infliximab [CT-P13] has recently been shown to be as effective as IV infliximab after two doses of IV induction in a randomised trial, but there are no data to support elective switching of patients on maintenance IV infliximab therapy. We aimed to assess the effectiveness of an elective switching programme to SC CT-P13 in patients treated with IV infliximab.