Investigation of cardiac substructure automatic segmentation methods on synthetically generated 4D cone-beam CT images.

Background: STereotactic Arrhythmia Radioablation (STAR) is a novel noninvasive method for treating arrythmias in which external beam radiation is directed towards subregions of the heart. Challenges for accurate STAR targeting include small target volumes and relatively large patient motion, which can lead to radiation related patient toxicities. 4D Cone-beam CT (CBCT) images are used for stereotactic lung treatments to account for respiration-related patient motion.

Similarity of Phenotype in Three Male Patients With the c.320A>G Variant in ALG13: Possible Genotype-Phenotype Correlation.

Background: Congenital disorders of glycosylation (CDG) are a group of neurometabolic diseases that result from genetic defects in the glycosylation of proteins and/or lipids. Multiple pathogenic genes contribute to the varying reported phenotypes of individuals with CDG-1 syndromes, most of which are inherited as autosomal recessive traits, although X-linked inheritance has also been reported. Pathogenic variants in the asparagine-linked glycosylation 13 homolog (ALG13) gene have been implicated in the aetiology of developmental and epileptic encephalopathy (DEE) 36 (OMIM:*300776, DEE36).

Overview of cardiac toxicity from radiation therapy.

Radiotherapy is an essential part of treatment for many patients with thoracic cancers. However, proximity of the heart to tumour targets can lead to cardiac side effects, with studies demonstrating link between cardiac radiation dose and adverse outcomes. Although reducing cardiac dose can reduce associated risks, most cardiac constraint recommendations in clinical use are generally based on dose to the whole heart, as dose assessment at cardiac substructure levels on individual patients has been limited historically.

Cardiac Substructure Dose and Survival in Stereotactic Radiotherapy for Lung Cancer: Results of the Multi-Centre SSBROC Trial.

Background And Purpose: Stereotactic ablative body radiotherapy (SABR) is increasingly used for early-stage lung cancer, however the impact of dose to the heart and cardiac substructures remains largely unknown. The study investigated doses received by cardiac substructures in SABR patients and impact on survival.

Materials And Methods: SSBROC is an Australian multi-centre phase II prospective study of SABR for stage I non-small cell lung cancer.

An interactive 3D atlas of sentinel lymph nodes in breast cancer developed using SPECT/CT.

Background: The identification and assessment of sentinel lymph nodes (SLNs) in breast cancer is important for optimised patient management. The aim of this study was to develop an interactive 3D breast SLN atlas and to perform statistical analyses of lymphatic drainage patterns and tumour prevalence.

Methods: A total of 861 early-stage breast cancer patients who underwent preoperative lymphoscintigraphy and SPECT/CT were included.

Gender and sex hormone effects on neonatal innate immune function.

Objectives: Scientific evidence provides a widened view of differences in immune response between male and female neonates. The X-chromosome codes for several genes important in the innate immune response and neonatal innate immune cells express receptors for, and are inhibited by, maternal sex hormones. We hypothesized that sex differences in innate immune responses may be present in the neonatal population which may contribute to the increased susceptibility of premature males to sepsis.

Cardiac substructure delineation in radiation therapy - A state-of-the-art review.

Delineation of cardiac substructures is crucial for a better understanding of radiation-related cardiotoxicities and to facilitate accurate and precise cardiac dose calculation for developing and applying risk models. This review examines recent advancements in cardiac substructure delineation in the radiation therapy (RT) context, aiming to provide a comprehensive overview of the current level of knowledge, challenges and future directions in this evolving field. Imaging used for RT planning presents challenges in reliably visualising cardiac anatomy.

Dosimetric Impact of Delineation and Motion Uncertainties on the Heart and Substructures in Lung Cancer Radiotherapy.

Aims: Delineation variations and organ motion produce difficult-to-quantify uncertainties in planned radiation doses to targets and organs at risk. Similar to manual contouring, most automatic segmentation tools generate single delineations per structure; however, this does not indicate the range of clinically acceptable delineations. This study develops a method to generate a range of automatic cardiac structure segmentations, incorporating motion and delineation uncertainty, and evaluates the dosimetric impact in lung cancer.

Towards optimal heterogeneous prostate radiotherapy dose prescriptions based on patient-specific or population-based biological features.

Background: Escalation of prescribed dose in prostate cancer (PCa) radiotherapy enables improvement in tumor control at the expense of increased toxicity. Opportunities for reduction of treatment toxicity may emerge if more efficient dose escalation can be achieved by redistributing the prescribed dose distribution according to the known heterogeneous, spatially-varying characteristics of the disease.

Purpose: To examine the potential benefits, limitations and characteristics of heterogeneous boost dose redistribution in PCa radiotherapy based on patient-specific and population-based spatial maps of tumor biological features.

An open source auto-segmentation algorithm for delineating heart and substructures - Development and validation within a multicenter lung cancer cohort.

Background And Purpose: Irradiation of the heart in thoracic cancers raises toxicity concerns. For accurate dose estimation, automated heart and substructure segmentation is potentially useful. In this study, a hybrid automatic segmentation is developed.

Realistic CT data augmentation for accurate deep-learning based segmentation of head and neck tumors in kV images acquired during radiation therapy.

Background: Using radiation therapy (RT) to treat head and neck (H&N) cancers requires precise targeting of the tumor to avoid damaging the surrounding healthy organs. Immobilisation masks and planning target volume margins are used to attempt to mitigate patient motion during treatment, however patient motion can still occur. Patient motion during RT can lead to decreased treatment effectiveness and a higher chance of treatment related side effects.

Validation of a Fully Automated Hybrid Deep Learning Cardiac Substructure Segmentation Tool for Contouring and Dose Evaluation in Lung Cancer Radiotherapy.

Background And Purpose: Accurate and consistent delineation of cardiac substructures is challenging. The aim of this work was to validate a novel segmentation tool for automatic delineation of cardiac structures and subsequent dose evaluation, with potential application in clinical settings and large-scale radiation-related cardiotoxicity studies.

Materials And Methods: A recently developed hybrid method for automatic segmentation of 18 cardiac structures, combining deep learning, multi-atlas mapping and geometric segmentation of small challenging substructures, was independently validated on 30 lung cancer cases.

Open-source, fully-automated hybrid cardiac substructure segmentation: development and optimisation.

Radiotherapy for thoracic and breast tumours is associated with a range of cardiotoxicities. Emerging evidence suggests cardiac substructure doses may be more predictive of specific outcomes, however, quantitative data necessary to develop clinical planning constraints is lacking. Retrospective analysis of patient data is required, which relies on accurate segmentation of cardiac substructures.

The BET inhibitor/degrader ARV-825 prolongs the growth arrest response to Fulvestrant + Palbociclib and suppresses proliferative recovery in ER-positive breast cancer.

Anti-estrogens or aromatase inhibitors in combination with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are the current standard of care for estrogen receptor-positive (ER+) Her-2 negative metastatic breast cancer. Although these combination therapies prolong progression-free survival compared to endocrine therapy alone, the growth-arrested state of residual tumor cells is clearly transient. Tumor cells that escape what might be considered a dormant or quiescent state and regain proliferative capacity often acquire resistance to further therapies.

Patient-specific voxel-level dose prescription for prostate cancer radiotherapy considering tumor cell density and grade distribution.

Background: In prostate radiation therapy, recent studies have indicated a benefit in increasing the dose to intraprostatic lesions (IPL) compared with standard whole gland radiation therapy. Such approaches typically aim to deliver a target dose to the IPL(s) with no deliberate effort to modulate the dose within the IPL. Prostate cancers demonstrate intra-tumor heterogeneity and hence it is hypothesized that further gains in the optimal delivery of radiation therapy can be achieved through modulation of the dose distribution within the tumor.

The hidden benefits of patient encounters.

Background: Whilst it is widely acknowledged that health care professionals (HCPs) learn from patient encounters, research exploring what HCPs learn from their meetings with patients is relatively sparse, particularly in the context of postgraduate training. Moreover, there are few research studies that examine the contribution of patient encounters to HCP education from both HCP and patient perspectives. This study set out to explore HCPs learning from patient encounters from both HCP and patient perspectives.

Therapeutic Potential for Targeting Autophagy in ER+ Breast Cancer.

While endocrine therapy remains the mainstay of treatment for ER-positive, HER2-negative breast cancer, tumor progression and disease recurrence limit the utility of current standards of care. While existing therapies may allow for a prolonged progression-free survival, however, the growth-arrested (essentially dormant) state of residual tumor cells is not permanent and is frequently a precursor to disease relapse. Tumor cells that escape dormancy and regain proliferative capacity also tend to acquire resistance to further therapies.

A statistical, voxelised model of prostate cancer for biologically optimised radiotherapy.

Background And Purpose: Radiation therapy (RT) is commonly indicated for treatment of prostate cancer (PC). Biologicallyoptimised RT for PC may improve disease-free survival. This requires accurate spatial localisation and characterisation of tumour lesions.

Modulating donor mitochondrial fusion/fission delivers immunoprotective effects in cardiac transplantation.

Early insults associated with cardiac transplantation increase the immunogenicity of donor microvascular endothelial cells (ECs), which interact with recipient alloreactive memory T cells and promote responses leading to allograft rejection. Thus, modulating EC immunogenicity could potentially alter T cell responses. Recent studies have shown modulating mitochondrial fusion/fission alters immune cell phenotype.

Paediatric management of a tuberculosis outbreak in an Irish Direct Provision Centre.

Direct Provision in Ireland provides basic needs of food and shelter to asylum seekers while their refugee status is processed. There are a number of issues associated with living conditions in these centres including overcrowding, nutrition and play facilities (1,2). This article outlines the protocol of contact tracing and management of latent tuberculosis infection in the paediatric setting after a confirmed adult case of tuberculosis within a Direct Provision centre in Ireland.

Autophagy-Dependent Sensitization of Triple-Negative Breast Cancer Models to Topoisomerase II Poisons by Inhibition of the Nucleosome Remodeling Factor.

Epigenetic regulators can modulate the effects of cancer therapeutics. To further these observations, we discovered that the bromodomain PHD finger transcription factor subunit (BPTF) of the nucleosome remodeling factor (NURF) promotes resistance to doxorubicin, etoposide, and paclitaxel in the 4T1 breast tumor cell line. BPTF functions in promoting resistance to doxorubicin and etoposide, but not paclitaxel, and may be selective to cancer cells, as a similar effect was not observed in embryonic stem cells.

Exploring parental experiences of virtual paediatric neurodevelopmental consultations.

Objective: The coronavirus pandemic resulted in dramatic changes and challenges to healthcare practices. We endeavoured to establish the experiences of families of children attending a neurodevelopmental service after a transition to virtual consultations.

Methods: Anonymous questionnaires were posted to parents of children registered in virtual clinics over a 10-week period.

Feasibility of using a novel automatic cardiac segmentation algorithm in the clinical routine of lung cancer patients.

Incidental radiation exposure to the heart during lung cancer radiotherapy is associated with radiation-induced heart disease and increased rates of mortality. By considering the respiratory-induced motion of the heart it is possible to create a radiotherapy plan that results in a lower overall cardiac dose. This approach is challenging using current clinical practices: manual contouring of the heart is time consuming, and subject to inter- and intra-observer variability.