Publications by authors named "Gunaratne P"

Active ankle orthoses which have been designed over the past few years by diverse sources were critically reviewed in this paper. It begins by providing an overview of the anatomy of the ankle joint complex, establishing a basis for understanding the subsequent discussion on the research challenges and design difficulties associated with developing active ankle orthosis devices. The review systematically examined the mechanisms, actuation methods, and control strategies utilized in these orthosis devices.

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  • The unfolded protein response (UPR) in skeletal muscle is activated during stress, but its role in muscle regeneration is not well understood.
  • In a study, researchers found that the gene XBP1, crucial for the UPR, is vital for muscle regeneration, as its absence hinders recovery in adult mice.
  • Analysis revealed that XBP1 affects both muscle cell function and the behavior of surrounding non-muscle cells, indicating that it plays a key role in muscle repair through multiple mechanisms.
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The epigenome is a target for environmental exposures and a potential determinant of inter-individual differences in response. In genetically identical C57Bl/6 mice exposed from gestation to weaning to the endocrine-disrupting chemical (EDC) tributyltin (TBT), hepatic tumor development later in life varied across multiple cohorts over time and depending on sex and diet. In one cohort where approximately half of TBT-exposed male mice developed liver tumors at 10 months (Katz et al.

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Skeletal muscle regeneration involves a signaling network that regulates the proliferation, differentiation, and fusion of muscle precursor cells to injured myofibers. IRE1α, one of the arms of the unfolded protein response, regulates cellular proteostasis in response to ER stress. Here, we demonstrate that inducible deletion of IRE1α in satellite cells of mice impairs skeletal muscle regeneration through inhibiting myoblast fusion.

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Aims: The mechanisms regulating the cellular behaviour and cardiomyocyte organization during ventricular wall morphogenesis are poorly understood. Cardiomyocytes are surrounded by extracellular matrix (ECM) and interact with ECM via integrins. This study aims to determine whether and how β1 integrins regulate cardiomyocyte behaviour and organization during ventricular wall morphogenesis in the mouse.

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Ischemic heart disease, a leading cause of death worldwide, manifests clinically as myocardial infarction. Contemporary therapies using mesenchymal stromal cells (MSCs) and their derivative (exosomes, EXOs) were developed to decrease the progression of cell damage during ischemic injury. Laminin alpha 2 (LAMA2) is an important extracellular matrix protein of the heart.

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Interferon gamma (IFNγ) is a critical cytokine known for its diverse roles in immune regulation, inflammation, and tumor surveillance. However, while IFNγ levels were elevated in sera of most newly diagnosed acute myeloid leukemia (AML) patients, its complex interplay in AML remains insufficiently understood. We aim to characterize these complex interactions through comprehensive bulk and single-cell approaches in bone marrow of newly diagnosed AML patients.

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Unlabelled: The p53 family member TP63 encodes two sets of N-terminal isoforms, TAp63 and ΔNp63 isoforms. They each regulate diverse biological functions in epidermal morphogenesis and in cancer. In the skin, where their activities have been extensively characterized, TAp63 prevents premature aging by regulating the quiescence and genomic stability of stem cells required for wound healing and hair regeneration, while ΔNp63 controls maintenance and terminal differentiation of epidermal basal cells.

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This article describes a monolayer-coated gold nanoparticle-based transfection system for the delivery of microRNA (miRNA) into human osteosarcoma (HOS) cells. Two distinct ammonium-terminated adsorbates were used in this study, which provided a platform for ionic bonding of the miRNA onto gold nanoparticles (AuNPs). The custom-designed monolayer-coated gold nanoparticles were characterized by dynamic light scattering, gel mobility shift assay, transmission electron microscopy, ultraviolet-visible spectrometry, zeta potential, and X-ray photoelectron spectroscopy.

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Skeletal muscle regeneration involves coordinated activation of an array of signaling pathways. Fibroblast growth factor-inducible 14 (Fn14) is a bona fide receptor for the TWEAK cytokine. Levels of Fn14 are increased in the skeletal muscle of mice after injury.

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Cell proliferation is a ubiquitous process required for organismal development and homeostasis. However, individuals with partial loss-of-function variants in DNA replicative helicase components often present with immunodeficiency due to specific loss of natural killer (NK) cells. Such lineage-specific disease phenotypes raise questions on how the proliferation is regulated in cell type-specific manner.

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Introduction: We present here a strategy to identify immunogenic neoantigen candidates from unique amino acid sequences at the junctions of fusion proteins which can serve as targets in the development of tumor vaccines for the treatment of breastcancer.

Method: We mined the sequence reads of breast tumor tissue that are usually discarded as discordant paired-end reads and discovered cancer specific fusion transcripts using tissue from cancer free controls as reference. Binding affinity predictions of novel peptide sequences crossing the fusion junction were analyzed by the MHC Class I binding predictor, MHCnuggets.

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Aims: The mechanisms regulating the cellular behavior and cardiomyocyte organization during ventricular wall morphogenesis are poorly understood. Cardiomyocytes are surrounded by extracellular matrix (ECM) and interact with ECM via integrins. This study aims to determine whether and how β1 integrins regulate cardiomyocyte behavior and organization during ventricular wall morphogenesis in the mouse.

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Background: Stroke registries are pivotal to the monitoring and improvement of the quality of stroke care. We report data from the initial phase of a nationally representative hospital-based stroke registry in Sri Lanka.

Methods: Based on an observational cohort design, all consecutive patients aged ≥18 years with a diagnosis of stroke or transient ischemic attack (TIA) presenting to six tertiary-care hospitals in the Western, Eastern, Southern, Northern and Central provinces of Sri Lanka within 14 days of onset were recruited.

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  • The study explores how tumor-associated nerves (TANs) interact with cancer and the immune system, particularly focusing on their role in resistance to anti-PD-1 therapy in cutaneous squamous cell carcinoma (cSCC).
  • Researchers found that cancer cells can damage TANs and myelin sheaths, leading to resistance against treatment.
  • The presence of high rates of peri-neural invasion and immune-suppressive activity was associated with non-responders to anti-PD-1 therapy, indicating potential therapeutic targets for improving outcomes in similar cancers.
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Coronavirus disease 2019 (COVID-19) causes severe illness in the immunocompromised. This study aimed to describe the severity and outcomes of kidney transplant recipients (KTRs) treated for COVID-19 during the first 16 months of the pandemic in Sri Lanka. We conducted a cross-sectional survey of all nephrology centers in Sri Lanka using a self-administered electronic data collection sheet.

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Background: Premature mortality in people with mental illness is well-documented, yet deaths during inpatient psychiatric care have received little research attention. This study investigates mortality rates and causes of death during inpatient psychiatric care in New South Wales (NSW), Australia. Risk factors for inpatient death were also explored.

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Objective: Drivers using level 2 automation are able to disengage with the dynamic driving task, but must still monitor the roadway and environment and be ready to takeover on short notice. However, people are still willing to engage with non-driving related tasks, and the ways in which people manage this tradeoff are expected to vary depending on the operational design domain of the system and the nature of the task. Our aim is to model driver gaze behavior in level 2 partial driving automation when the driver is engaged in an email task on a cell phone.

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With higher levels of automation in vehicles, the need for robust driver monitoring systems increases, since it must be ensured that the driver can intervene at any moment. Drowsiness, stress and alcohol are still the main sources of driver distraction. However, physiological problems such as heart attacks and strokes also exhibit a significant risk for driver safety, especially with respect to the ageing population.

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Introduction: To understand mechanisms and identify potential targets for intervention in the current crisis of opioid use disorder (OUD), postmortem brains represent an under-utilized resource. To refine previously reported gene signatures of neurobiological alterations in OUD from the dorsolateral prefrontal cortex (Brodmann Area 9, BA9), we explored the role of microRNAs (miRNA) as powerful epigenetic regulators of gene function.

Methods: Building on the growing appreciation that miRNAs can cross the blood-brain barrier, we carried out miRNA profiling in same-subject postmortem samples from BA9 and blood tissues.

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Currently, there are no treatments that ameliorate cardiac cell death, the underlying basis of cardiovascular disease. An unexplored cell type in cardiac regeneration is cardiac Purkinje cells; specialized cells from the cardiac conduction system (CCS) responsible for propagating electrical signals. Purkinje cells have tremendous potential as a regenerative treatment because they may intrinsically integrate with the CCS of a recipient myocardium, resulting in more efficient electrical conduction in diseased hearts.

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Aim: The purpose of this study was to evaluate whether a neurology outreach teaching programme delivered via video-teleconferencing (6 × 60 min live sessions every 6-8 weeks) is acceptable, contributes to understanding and meets the neurology learning needs of Australian paediatricians from metropolitan, rural and remote areas.

Methods: A sample of six NSW sites that joined the neurology outreach programme between 2017 and 2019 (Arm 1) and six interstate sites from QLD, WA and TAS who commenced the programme in 2020 (Arm 2) participated. A mixed-methods survey explored participants' learning needs and value of the programme.

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  • Non-small cell lung cancer (NSCLC), which includes lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), represents about 85% of lung tumors, and this study aimed to find unique metabolite-related gene signatures and their altered metabolic pathways for these types.
  • The research integrated transcriptomics (gene expression) and metabolomics (metabolite profiling) from 30 human lung tumors to discover differences in metabolites between cancerous and noncancerous tissues.
  • The study identified distinct metabolic gene signatures for LUAD and LUSC, revealing that altered metabolites and gene expressions are linked to poor survival in LUAD, which could guide the use of drugs like AZD-6482 as
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Hepatoblastoma (HB) is the most common pediatric primary liver malignancy, and survival for high-risk disease approaches 50%. Mouse models of HB fail to recapitulate hallmarks of high-risk disease. The aim of this work was to generate murine models that show high-risk features including multifocal tumors, vascular invasion, metastasis, and circulating tumor cells (CTCs).

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