Intrafraction motion in intra-cranial multi-target stereotactic radiosurgery plans: A multi-institutional investigation on robustness.

Purpose: Even with modern immobilisation devices, some amount of intrafraction patient motion is likely to occur during stereotactic radiosurgery (SRS) delivery. The aim of this work was to investigate how robustness of plans to intrafraction motion is affected by plan geometry and complexity.

Methods: In 2018, the Trans-Tasman Radiation Oncology Group conducted a multiple-target SRS international planning challenge, the data from which was utilised in this study.

Technical considerations of cardiac computed tomography in children.

Cardiac computed tomography angiography (CTA) is a valuable tool in the assessment of congenital and acquired cardiac disease in children. The goal of cardiac CTA is to produce images that are free of motion and provide sufficient characterization of the anatomy in question. Given the complexity of pediatric patient characteristics, including patient size, heart rate, breath-holding capability, and variant anatomy, cardiac CTA technique must be individualized to the patient as well as the indication to answer the clinical question while also minimizing radiation exposure.

Establishing the green algae as a platform for recombinant protein production.

, a genetically close relative of the model green alga , shows significant potential as a host for recombinant protein expression. Because of the close genetic relationship between and , this species offers an additional reference point for advancing our understanding of photosynthetic organisms, and also provides a potential new candidate for biotechnological applications. This study investigates C.

The Innate Immune System and the TRAIL-Bcl-XL Axis Mediate a Sex Bias in Lung Cancer and Confer a Therapeutic Vulnerability in Females.

There is a significant sex bias in lung cancer, with males showing increased mortality compared with females. A better mechanistic understanding of these differences could help identify therapeutic targets to personalize cancer therapies to each sex. After observing a clear sex bias in humanized mice, with male patient-derived xenograft lung tumors being more progressive and deadlier than female patient-derived xenograft lung tumors, we identified mouse tumor models of lung cancer with the same sex bias.

Biased receptor signalling and intracellular trafficking profiles of structurally distinct formylpeptide receptor 2 agonists.

Background: There is increasing interest in developing FPR2 agonists (compound 43, ACT-389949 and BMS-986235) as potential pro-resolving therapeutics, with ACT-389949 and BMS-986235 having entered phase I clinical development. FPR2 activation leads to diverse downstream outputs. ACT-389949 was observed to cause rapid tachyphylaxis, while BMS-986235 and compound 43 induced cardioprotective effects in preclinical models.

Multi-institutional investigation into the robustness of intra-cranial multi-target stereotactic radiosurgery plans to patient setup errors.

Purpose: This study aimed to analyse correlations between planning factors including plan geometry and plan complexity with robustness to patient setup errors.

Methods: Multiple-target brain stereotactic radiosurgery (SRS) plans were obtained through the Trans-Tasman Radiation Oncology Group (TROG) international treatment planning challenge (2018). The challenge dataset consisted of five intra-cranial targets with a 20 Gy prescription.

Highlights and hot topics in GPCR research from 'Down Under'.

This article is part of a themed issue Therapeutic Targeting of G Protein-Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.

Feeding Ration Impacts Larval Pimephales Promelas 7-Day Subchronic Growth Endpoint: Case Study with Perfluorooctanesulfonic Acid.

The larval fathead minnow, Pimephales promelas, 7-day subchronic survival and growth standard toxicity test method is commonly used for research and regulatory testing of effluents and compounds, including emerging contaminants such as Perfluorooctanesulfonic Acid (PFOS). Existing feeding guidelines for testing are described in multiple methods but are open to interpretation. The current study sought to determine the impact of feeding ration on P.

Development of Putative Bivalent Dicovalent Ligands for the Adenosine A1 Receptor.

Accumulating evidence suggests that G protein-coupled receptors (GPCRs) can exist and function in homodimer and heterodimer forms. The adenosine A1 receptor (AR) has been shown to form both homodimers and heterodimers, but there is a lack of chemical tools to study these dimeric receptor populations. This work describes the synthesis and pharmacological evaluation of a novel class of bivalent GPCR chemical tools, where each ligand moiety of the bivalent compound contains a sulfonyl fluoride covalent warhead designed to be capable of simultaneously reacting with each AR of an AR homodimer.

The role of an abbreviated ultrasound in the evaluation of necrotizing enterocolitis.

Background: Bowel ultrasound is a useful diagnostic tool in the diagnosis and management of necrotizing enterocolitis (NEC) but can be time-consuming and requires technical expertise, particularly for assessing pneumatosis. Previous literature on sonographic evaluation of NEC has focused on a full bowel ultrasound protocol, but the utility of an abbreviated protocol primarily aimed at identifying high-risk sonographic findings without focused bowel assessment has not been well studied.

Objective: This study aims to describe the diagnostic accuracy of an abbreviated ultrasound protocol for identifying high-risk NEC findings.

GraphormerDTI: A graph transformer-based approach for drug-target interaction prediction.

The application of Artificial Intelligence (AI) to screen drug molecules with potential therapeutic effects has revolutionized the drug discovery process, with significantly lower economic cost and time consumption than the traditional drug discovery pipeline. With the great power of AI, it is possible to rapidly search the vast chemical space for potential drug-target interactions (DTIs) between candidate drug molecules and disease protein targets. However, only a small proportion of molecules have labelled DTIs, consequently limiting the performance of AI-based drug screening.

Pelvic Floor Dysfunction Among Persons With Marfan and Loeys-Dietz Syndrome.

Importance: Connective tissue disorders are proposed in the literature to be predisposing risk factors for pelvic floor disorders. Prior data characterizing the prevalence of and symptom burden related to pelvic floor disorders are limited for individuals with Marfan syndrome and are nonexistent for those with Loeys-Dietz syndrome.

Objective: The objective of this study was to determine the prevalence and severity of symptoms related to pelvic floor disorders among individuals with Marfan syndrome and Loeys-Dietz syndrome using the Pelvic Floor Distress Inventory-20 (PFDI-20).

Small molecule allosteric modulation of the adenosine A receptor.

G protein-coupled receptors (GPCRs) represent the target for approximately a third of FDA-approved small molecule drugs. The adenosine A receptor (AR), one of four adenosine GPCR subtypes, has important (patho)physiological roles in humans. AR has well-established roles in the regulation of the cardiovascular and nervous systems, where it has been identified as a potential therapeutic target for a number of conditions, including cardiac ischemia-reperfusion injury, cognition, epilepsy, and neuropathic pain.

Structure-based virtual screening discovers potent and selective adenosine A receptor antagonists.

Development of subtype-selective leads is essential in drug discovery campaigns targeting G protein-coupled receptors (GPCRs). Herein, a structure-based virtual screening approach to rationally design subtype-selective ligands was applied to the A and A adenosine receptors (AR and AR). Crystal structures of these closely related subtypes revealed a non-conserved subpocket in the binding sites that could be exploited to identify AR selective ligands.

The application of artificial intelligence to accelerate G protein-coupled receptor drug discovery.

The application of artificial intelligence (AI) approaches to drug discovery for G protein-coupled receptors (GPCRs) is a rapidly expanding area. Artificial intelligence can be used at multiple stages during the drug discovery process, from aiding our understanding of the fundamental actions of GPCRs to the discovery of new ligand-GPCR interactions or the prediction of clinical responses. Here, we provide an overview of the concepts behind artificial intelligence, including the subfields of machine learning and deep learning.

Targeting G protein-coupled receptors for heart failure treatment.

Heart failure remains a leading cause of morbidity and mortality worldwide. Current treatment for patients with heart failure include drugs targeting G protein-coupled receptors such as β-adrenoceptor antagonists (β-blockers) and angiotensin II type 1 receptor antagonists (or angiotensin II receptor blockers). However, many patients progress to advanced heart failure with persistent symptoms, despite treatment with available therapeutics that have been shown to reduce mortality and mortality.

The role of the adenosine system in epilepsy and its comorbidities.

Epilepsy is one of the most serious and common chronic neurological conditions, characterised by recurrent hypersynchronous electrical activity in the brain that lead to seizures. Despite over 50 million people being affected worldwide, only ~70% of people with epilepsy have their seizures successfully controlled with current pharmacotherapy, and many experience significant psychiatric and physical comorbidities. Adenosine, a ubiquitous purine metabolite, is a potent endogenous anti-epileptic substance that can abolish seizure activity via the adenosine A G protein-coupled receptor.

The epigenetic regulation of cancer cell recovery from therapy exposure and its implications as a novel therapeutic strategy for preventing disease recurrence.

The ultimate goal of cancer therapy is the elimination of disease from patients. Most directly, this occurs through therapy-induced cell death. Therapy-induced growth arrest can also be a desirable outcome, if prolonged.

The impact of cryo-EM on determining allosteric modulator-bound structures of G protein-coupled receptors.

G-protein coupled receptors (GPCRs) are important therapeutic targets for the treatment of human disease. Although GPCRs are highly successful drug targets, there are many challenges associated with the discovery and translation of small molecule ligands that target the endogenous ligand-binding site for GPCRs. Allosteric modulators are a class of ligands that target alternative binding sites known as allosteric sites and offer fresh opportunities for the development of new therapeutics.