A genome-wide association study for recurrent laryngeal neuropathy in the Thoroughbred horse identifies a candidate gene that regulates myelin structure.

Background: Equine recurrent laryngeal neuropathy (RLN) is an economically important upper respiratory tract (URT) disease with a genetic contribution to risk, but genetic variants independent of height have not been identified for Thoroughbreds. The method of clinical assessment for RLN is critical to accurately phenotype groups for genetic studies.

Objectives: To identify genetic risk loci for RLN in Thoroughbreds in a genome-wide association study (GWAS) following high-resolution phenotyping.

KPRR: a novel machine learning approach for effectively capturing nonadditive effects in genomic prediction.

Nonadditive genetic effects pose significant challenges to traditional genomic selection methods for quantitative traits. Machine learning approaches, particularly kernel-based methods, offer promising solutions to overcome these limitations. In this study, we developed a novel machine learning method, KPRR, which integrated a polynomial kernel into ridge regression to effectively capture nonadditive genetic effects.

Targeting Radiation Resistance in Oesophageal Adenocarcinoma with Pyrazinib-Functionalised Gold Nanoparticles.

Unlabelled: Only 20-30% of oesophageal adenocarcinoma (OAC) patients achieve a complete response to neoadjuvant chemo-radiotherapy for locally advanced tumours. Enhancing the response to radiation therapy is critical for improving outcomes in this aggressive cancer. Pyrazinib (P3) is a promising compound with radiosensitizing, anti-angiogenic, anti-inflammatory, and anti-metabolic properties.

Comparative analysis of WC1.1+ and WC1.2+ γδ T cell subset responses from cattle naturally infected with Mycobacterium bovis to repeat stimulation with mycobacterial antigens.

Mycobacterium bovis (M. bovis) causes bovine tuberculosis (bTB). The challenges in controlling and eradicating this zoonotic disease are compounded by our incomplete understanding of the host immune response.

Validation requirements for AI-based intervention-evaluation in aging and longevity research and practice.

The field of aging and longevity research is overwhelmed by vast amounts of data, calling for the use of Artificial Intelligence (AI), including Large Language Models (LLMs), for the evaluation of geroprotective interventions. Such evaluations should be correct, useful, comprehensive, explainable, and they should consider causality, interdisciplinarity, adherence to standards, longitudinal data and known aging biology. In particular, comprehensive analyses should go beyond comparing data based on canonical biomedical databases, suggesting the use of AI to interpret changes in biomarkers and outcomes.

Examining the evidence for immune checkpoint therapy in high-grade serous ovarian cancer.

The 5-year survival rate for ovarian cancer has remained relatively static over the past number of years, which can be attributed in part to the lack of new therapeutic strategies to target this disease. Although numerous other cancer types have benefited from the success of immune checkpoint inhibitors, their use in clinical trials targeting ovarian cancer has shown limited efficacy. Most clinical trials have focused on PD-1/PD-L1 immune checkpoint blockade, either as a monotherapy or in combination with chemotherapies, however inhibiting other pathways may potentially be more efficacious in treating ovarian cancer.

Machine learning and artificial intelligence: Enabling the clinical translation of atomic force microscopy-based biomarkers for cancer diagnosis.

The influence of biomechanics on cell function has become increasingly defined over recent years. Biomechanical changes are known to affect oncogenesis; however, these effects are not yet fully understood. Atomic force microscopy (AFM) is the gold standard method for measuring tissue mechanics on the micro- or nano-scale.

Health Benefits Beyond the Scale: The Role of Diet and Nutrition During Weight Loss Programmes.

Introduction: Obesity management strategies such as caloric restriction, very-low-calorie diets (VLCDs), and meal replacements can lead to moderate short-term weight loss. However, many patients face significant challenges in maintaining these results. Personalized interventions, including behavioral counseling and physical activity, have been shown to improve long-term adherence and success.

Oxyntomodulin physiology and its therapeutic development in obesity and associated complications.

Incretins, such as glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP), have advanced the treatment landscape of obesity to a new pinnacle. As opposed to singular incretin effects, oxyntomodulin (OXM) activates glucagon receptors (GCGR) and glucagon-like peptide-1 receptors (GLP1R), demonstrating a more dynamic range of effects that are more likely to align with evolving 'health gains' goals in obesity care. Here, we will review the molecular insights from their inception to recent developments and challenges.

Transcriptional regulation of hypoxic cancer cell metabolism and artificial intelligence.

Gene expression regulation in hypoxic tumor microenvironments is mediated by O responsive transcription factors (OR-TFs), fine-tuning cancer cell metabolic demand for O according to its availability. Here, we discuss key OR-TFs and emerging artificial intelligence (AI)-based applications suitable for the interrogation of OR-TF relationships specifying cancer cell metabolic adaptations to hypoxia.

Origins and molecular effects of hypoxia in cancer.

Hypoxia (insufficient O) is a pivotal factor in cancer progression, triggering genetic, transcriptional, translational and epigenetic adaptations associated to therapy resistance, metastasis and patient mortality. In this review, we outline the microenvironmental origins and molecular mechanisms responsible for hypoxic cancer cell adaptations in situ and in vitro, whilst outlining current approaches to stratify, quantify and therapeutically target hypoxia in the context of precision oncology.

The Impact of Varying Pasture Levels on the Metabolomic Profile of Bovine Ruminal Fluid.

A pasture or concentrate-based dietary regime impacts a variety of factors including both ruminal health and function, and consequently milk production and quality. The objective of this study was to examine the effect of feeding differing pasture levels on the metabolite composition of bovine ruminal fluid. Ruminal fluid was obtained from rumen-cannulated spring-calving cows (N = 9, Holstein-Friesian breed, average lactation number = 5) fed one of three diets across a full lactation season.

Proteomic Characterisation of Heart Failure Reveals a Unique Molecular Phenotype for Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a disease, which is difficult to diagnose at an early stage and for which there is a pressing need for more effective treatment options. The purpose of this study was to compare the molecular profile of HCM to that of ischaemic cardiomyopathy (ISCM) and dilated cardiomyopathy (DCM) for identification of protein and pathway targets that could support the development of better diagnostic and treatment options for HCM. A high-throughput mass spectrometry workflow was applied to achieve deep quantitative coverage of left ventricular tissue from HCM, DCM, ISCM and non-heart-failure control patients.

Extensive differential DNA methylation between tuberculosis skin test positive and skin test negative cattle.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis (M. bovis), represents a significant problem for the agriculture industry as well as posing a risk for human health. Current diagnostic tests for bTB target the cell-mediated immune (CMI) response to infection with M.

Impact of dietary regime on the metabolomic profile of bovine buttermilk and whole milk powder.

Introduction: Bovine milk contains a rich matrix of nutrients such as carbohydrates, fat, protein and various vitamins and minerals, the composition of which is altered by factors including dietary regime.

Objectives: The objective of this research was to investigate the impact of dietary regime on the metabolite composition of bovine whole milk powder and buttermilk.

Methods: Bovine whole milk powder and buttermilk samples were obtained from spring-calving cows, consuming one of three diets.

Association of plant-based diet indexes with the metabolomic profile.

Plant-based diets have gained attention for their potential benefits on both human health and environmental sustainability. The objective of this study was to investigate the association of plant-based dietary patterns with the endogenous metabolites of healthy individuals and identify metabolites that may act as mediators of the associations between dietary intake and modifiable disease risk factors. Adherence to plant-based dietary patterns was assessed for 170 healthy adults using plant-based diet indexes (PDI).

Effect of conventional and novel techniques on extraction yield, chemical characterisation and biological activities of proteins from bitter gourd (Momordica charantia).

The study investigates the effect of conventional and novel extraction techniques on the protein extraction yield from bitter gourd seeds (Momordica charantia). Ultrasound assisted-extraction (UAE) treatment for 30 min at 4 °C using a 20 kHz ultrasound probe resulted in the highest extraction yield of crude proteins. After purification, 9.

Effect of hypercholesterolemia on circulating and cardiomyocyte-derived extracellular vesicles.

Hypercholesterolemia (HC) induces, propagates and exacerbates cardiovascular diseases via various mechanisms that are yet not properly understood. Extracellular vesicles (EVs) are involved in the pathomechanism of these diseases. To understand how circulating or cardiac-derived EVs could affect myocardial functions, we analyzed the metabolomic profile of circulating EVs, and we performed an in-depth analysis of cardiomyocyte (CM)-derived EVs in HC.

Impact of increased protein intake in older adults: a 12-week double-blind randomised controlled trial.

Background: Emerging evidence suggests health-promoting properties of increased protein intake. There is increased interest in plant protein but a dearth of information in relation to its impact on muscle function. The objective of the present work was to examine the impact of intake of different types of proteins on muscle functional parameters including handgrip strength, biomarkers of metabolic health, sleep quality and quality of life in a group of older adults.