Circulating Trimethylamine N-Oxide and Growth Rate of Abdominal Aortic Aneurysms and Surgical Risk.

Importance: Plasma levels of the gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) are associated with prevalent abdominal aortic aneurysms (AAA) in humans and fostering of AAA progression in animal models; therapeutic targeting of TMAO production blocks AAA progression and rupture in multiple mouse models. A blood biomarker that identifies individuals at risk for incident AAA development, accelerated AAA expansion, or recommendation for surgical AAA repair could be an asset for risk stratification.

Objective: To determine whether TMAO is associated with risk for AAA development, rapid AAA expansion, and risk for recommended surgical intervention.

Potential Multiaxial Molecular Ferroelectricity through Chiral Cation Replacement.

Molecular ferroelectrics are an important class of materials offering chemical versatility, low toxicity, and tunable functional properties. A major design challenge lies in achieving multiaxial properties akin to inorganic perovskite ferroelectrics. Here, we report a series of new potential multiaxial molecular ferroelectrics obtained by introducing chiral cations into a structure type known to undergo a phase transition that raises the symmetry significantly.

Cellular and enzymatic features of thrombi in humans are vascular bed dependent.

Mechanisms behind vascular remodeling following thrombosis are unclear. Although acute arterial thrombosis in the cerebrovascular circulation has devastating consequences and requires immediate attention, the management of venous thromboembolism (VTE) varies significantly. Our goal was to determine the molecular signatures and cellular content of thrombus extracted using a catheter to gain insight into vascular remodeling.

Evaluating the efficacy of antiplatelet therapy in spontaneous coronary artery dissection: a scoping review.

Background: Spontaneous coronary artery dissection (SCAD) is a poorly-studied cause of acute coronary syndrome (ACS), particularly in women. SCAD is a rare cause of ACS that can lead to myocardial injury due to SCAD. This review evaluates optimal antiplatelet therapy for SCAD patients.

Preschool Oral Immunotherapy Is Associated With Improved Parental Food Allergy-Specific Anxiety and Quality of Life: A Real-World Observational Study.

Introduction: Preschool oral immunotherapy (OIT) is safe and effective for food allergy, and may improve parental food allergy-specific anxiety (FAA) and food allergy quality of life (FAQL); however, data on these important outcomes are limited, particularly for preschoolers. Herein, we explored the relationship between OIT and parental FAA, including the subdomains: food allergy-related worries, anxiety impact, behavioural avoidance, and coping; and OIT and FAQL in parents of preschool-aged children.

Methods: Parents of preschool-aged children (< 72 months) receiving OIT in Canadian allergy clinics were eligible for this observational study.

Impact of Atherosclerotic Conditions and Cardiovascular Medications on Abdominal Aortic Aneurysm Growth.

Background: While risk factors for atherosclerotic diseases and abdominal aortic aneurysms overlap, some risk factors, like diabetes, may slow aneurysm growth. The impact of atherosclerosis and its treatment on aneurysm growth is unknown. We aimed to investigate whether atherosclerotic conditions and cardiovascular medications are associated with faster aneurysm growth.

Model systems and unique biological features of high and low-grade colorectal cancer (CRC) revealed by xenografting 84 human CRC cell lines.

Colorectal cancers (CRCs) present across a range of differentiation grades, which impact patient outcome and management; however, the molecular features and drivers of differentiation status are not fully understood. To address this, 84 commonly used human CRC cell lines were grown as xenografts in mice, revealing models of low-grade (LG) and high-grade (HG) CRC. Transcriptional profiling revealed coordinate downregulation of multiple transcription factors involved in intestinal development and differentiation, markers of colonic lineage-specific differentiation, and effectors of normal functions of the colonic epithelium in HG tumours.

A Proposed Framework for an Interdisciplinary Food Allergy Immunotherapy Program for Pediatric Patients Transitioning to Adult Care.

Although established frameworks and guidelines are available to help transition pediatric patients successfully to adult care, patients receiving food allergy immunotherapy have a unique set of needs, and challenges that must be considered. We highlight these considerations for a research-based tertiary care center immunotherapy program. A proposed framework for an interdisciplinary food allergy immunotherapy team that includes not only pediatric allergists and nursing but also adult allergists, dietitians, researchers, and mental health team members working synergistically to address the needs of adolescents and young adults undergoing food allergy immunotherapy as they transition to adult care is presented.

Impacts of Nantucket pine tip moth, Rhyacionia frustrana (Lepidoptera: Tortricidae) management on rotation-length economic returns of loblolly pine.

The Nantucket pine tip moth, Rhyacionia frustrana, is primarily a pest of young pines (Pinus L.) in the southern United States and parts of Central America. Feeding damage can result in terminal mortality, stunted tree growth, and occasional tree death.

Biomechanical platelet activation: diseases that require a new class of antiplatelet therapeutics.

Mechanisms of platelet activation have traditionally been investigated through the activation of biochemical pathways through cell surface agonists such as adenosine diphosphate, thrombin, and collagen. However, recent research has identified another crucial mechanism, biomechanical activation, where external physical forces directly influence platelet reactivity. This paradigm shift underscores the complex interplay between biochemical and biomechanical stimuli in platelet activation.

Protein sequence modelling with Bayesian flow networks.

Exploring the vast and largely uncharted territory of amino acid sequences is crucial for understanding complex protein functions and the engineering of novel therapeutic proteins. Whilst generative machine learning has advanced protein sequence modelling, no existing approach is proficient in both unconditional and conditional generation. In this work, we propose that Bayesian Flow Networks (BFNs), a recently introduced framework for generative modelling, can address these challenges.

Transmission, Spread, Longevity and Management of Hop Latent Viroid, a Widespread and Destructive Pathogen Affecting Cannabis ( L.) Plants in North America.

Hop latent viroid (HLVd), a 256-nucleotide RNA strand with complementary base-pairing and internal stem loop structures, forms circular or rod-shaped molecules within diseased plants. RT-PCR/RT-qPCR was used to assess HLVd transmission, spread and longevity. The viroid was detected in asymptomatic stock plants and in rooted vegetative cuttings, as well as in recirculated nutrient solution sampled from propagation tables and nozzles.

Oral Immunotherapy Should Play a Key Role in Preschool Food Allergy Management.

Food allergies pose significant challenges including the risk for severe allergic reactions. This review article highlights the advantages and disadvantages of the historic standard management approach-avoidance and carrying epinephrine in case of accidental ingestion-and argues, based on accumulating evidence, that oral immunotherapy (OIT) should play a key role in preschool food allergy management. Firstly, our review will highlight pitfalls with the 'wait-and-see' approach to natural resolution of food allergies, with recent data pointing to lower resolution than previously thought.

Protection of β2GPI-deficient mice from thrombosis reflects a defect in PAR3-facilitated platelet activation.

Antibodies to β2-glycoprotein I (β2GPI) cause thrombosis in antiphospholipid syndrome; however, the role of β2GPI in coagulation in vivo is not understood. To address this issue, we developed β2GPI-deficient mice (Apoh-/-) by deleting exons 2 and 3 of Apoh using CRISPR/Cas9 and compared the development of thrombosis in wild-type (WT) and Apoh-/- mice using rose bengal- and FeCl3-induced carotid thrombosis, laser-induced cremaster arteriolar injury, and inferior vena cava (IVC) stasis models. We also compared tail bleeding times and activation of platelets from WT and Apoh-/- mice in the absence and presence of β2GPI.

VTE incidence shortens survival in IDH-WT glioblastoma.

Background: Venous thromboembolisms (VTE's) are the second leading cause of death in cancer patients. While previous analyses have demonstrated VTE rates are greater in GBM patients using smaller patient cohorts in high-grade glioma, since the release of the update 5 edition of the World Health Organization (WHO) classification a systematic analysis in a large-scale cohort of patients with IDH-wildtype GBM with clinical outcomes is lacking.

Methods: This study utilizes the online database, TriNetx, to build patient cohorts for outcomes analysis.

Four-electron reduction of benzene by a samarium(II)-alkyl without the addition of external reducing agents.

Benzene reduction by molecular complexes remains an important synthetic challenge, requiring harsh reaction conditions involving group I metals. Reductions of benzene, to date, typically result in a loss of aromaticity, although the benzene tetra-anion, a 10π-electron system, has been calculated to be stable and aromatic. Due to the lack of sufficiently potent reductants, four-electron reduction of benzene usually requires the use of group I metals.

Developing and disseminating an electronic penicillin allergy de-labelling tool using the model for improvement framework.

Background: Many clinicians feel uncomfortable with de-labelling penicillin allergies despite ample safety data. Point of care tools effectively support providers with de-labelling. This study's objective was to increase the number of providers intending to pursue a penicillin oral challenge by 15% by February 2023.

Natural and Semisynthetic Immunomodulatory Luakuliide Labdane Diterpenoids.

Spectroscopy-guided isolation of extracts of the Tongan marine sponge cf. (Lamarck, 1814) has resulted in the reisolation of the labdane diterpenoid luakuliide A () and one new congener, luakulialactam A (). In addition to establishing the absolute configuration of , synthetic modifications to the luakuliide framework at key positions has created a set of six derivatives (-) which were used to interrogate a structure-activity relationship relating to the immunomodulatory effects of luakuliide A.

Universal Polar Instability in Highly Orthorhombic Perovskites.

The design of novel multiferroic ABO perovskites is complicated by the presence of necessary magnetic cations and ubiquitous antiferrodistortive modes, both of which suppress polar distortions. Using first-principles simulations, we observe that the existence of quadlinear and trilinear invariants in the free energy, coupling tilts, and antipolar motions of A and B sites to the polar mode drives an avalanche-like transition to a non-centrosymmetric 2 symmetry in a wide range of magnetic perovskites with small tolerance factors, overcoming the above restrictions. We find that the 2 phase is especially favored with tensile epitaxial strain, leading to an unexpected but technologically useful out-of-plane polarization.

Real-world experience: a retrospective pediatric chart review to determine why patients and caregivers discontinue oral immunotherapy.

Background: Oral immunotherapy (OIT) is an increasingly utilized management strategy for IgE-mediated food allergy. Despite promising efficacy and effectiveness, there is still a lack of data surrounding the reasons for discontinuation of OIT. The primary reason stated in the literature for discontinuation is adverse gastrointestinal effects.

An efficient regioconvergent synthesis of 3-aza-obeticholic acid.

Bile acids (BAs) are steroidal molecules that play important roles in nutrient absorption, distribution, and excretion. They also act on specific receptors implicated in various metabolic and inflammatory diseases demonstrating their importance as potential drug candidates. Accordingly, there has been a concerted effort to develop new BA derivatives to probe structure-activity relationships with the goal of discovering BA analogues with enhanced pharmacological properties.