19683 research outputs found
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Unveiling a Health Disparity: Comparative Analysis of Head and Neck Cancer Trends between First Nations People and Non-Indigenous Australians (1998–2015)
No full textBackground: We aim to assess and compare the HNC trends between the First Nations and non-Indigenous population. Methods: HNC incidence (1998–2013) and mortality (1998–2015) data in First Nations people and non-Indigenous Australians were utilised from the Australian Cancer Database. The age-standardised incidence and mortality trends along with annual percentage changes were analysed using Joinpoint models. Age-standardised incidence and mortality rates according to remoteness, states, and five-year survival rates among First Nations people and non-Indigenous Australians were presented as graphs. Results: First Nations people had over twice the age-standardised incidence (2013; 29.8/100,000 vs. 14.7/100,000) and over 3.5 times the age-standardised mortality rates (2015; 14.2/100,000 vs. 4.1/100,000) than their non-Indigenous counterparts. Both populations saw a decline in mortality, but the decline was only statistically significant in non-Indigenous Australians (17.1% decline, 1998: 4.8/100,000, 2015: 4.1/100,000; p < 0.05). Across all remoteness levels and states, First Nations people consistently had higher age-standardised incidence and mortality rates. Furthermore, the five-year survival rate was lower by 25% in First Nations people. Conclusion: First Nations people continue to shoulder a disproportionate HNC burden compared to non-Indigenous Australians
Vitamin D Receptor Regulates the Expression of the Grainyhead-Like 1 Gene
No full textVitamin D plays an important pleiotropic role in maintaining global homeostasis of the human body. Its functions go far beyond skeletal health, playing a crucial role in a plethora of cellular functions, as well as in extraskeletal health, ensuring the proper functioning of multiple human organs, including the skin. Genes from the Grainyhead-like (GRHL) family code for transcription factors necessary for the development and maintenance of various epithelia. Even though they are involved in many processes regulated by vitamin D, a direct link between vitamin D-mediated cellular pathways and GRHL genes has never been described. We employed various bioinformatic methods, quantitative real-time PCR, chromatin immunoprecipitation, reporter gene assays, and calcitriol treatments to investigate this issue. We report that the vitamin D receptor (VDR) binds to a regulatory region of the Grainyhead-like 1 (GRHL1) gene and regulates its expression. Ectopic expression of VDR and treatment with calcitriol alters the expression of the GRHL1 gene. The evidence presented here indicates a role of VDR in the regulation of expression of GRHL1 and correspondingly a role of GRHL1 in mediating the actions of vitamin D
Experiences and challenges of acute coronary syndrome patients in care provision: a qualitative systematic review
No full textBackground: Coronary artery disease including acute coronary syndrome (ACS) constitutes the most common cause of death in people with cardiovascular disease. Prompt diagnosis and early initiation of treatment significantly impact on patient outcomes. Positive patient experience with their initial care is linked to positive clinical outcomes. Objective: This qualitative review aimed to investigate patients’ experience of care provision and the challenges faced by them during their different stages of care following an ACS. Methods: Searches of four databases - MEDLINE, Embase, CINAHL and PsychINFO - were conducted from inception until July 13, 2022, and were limited to English-language publications. Assessment of methodological quality of studies was performed using the Jonna Briggs Institute (JBI) qualitative assessment and review instrument. Data were extracted using the standardised data extraction tool from JBI. Data synthesis following the JBI approach of meta-aggregation was performed. The level of confidence for each synthesised finding was established based on ConQual. Results: Overall, from 578 records, 10 studies were included with 39 findings extracted from the included studies. The main synthesised findings were the need to provide tailored information and appropriate management at different stages of care, and that timely management and trust in health care workers are associated with greater patient satisfaction and more positive experiences. Conclusion: Patients with an ACS experience many challenges during different stages of their care. Clinicians should be aware of the challenges they face and provide tailored information to patients that is appropriate for their different stages of management in order to best optimise patient experience and improve patient outcomes
Public T cell clonotypes are selected in HLA-B∗57:01+/HIV+ patients independently of the viral load
No full textHIV controllers can control viral replication and remain healthy, but the mechanism behind this control is unknown. Despite human leukocyte antigen (HLA) diversity in the population, almost 50% of HIV controllers express the HLA-B∗57:01 molecule, which presents, among others, the Gag-derived epitope TW10. Given TW10’s presentation in early infection, TW10-specific T cells could participate in the control of HIV. Here, we study the strength and functionality of TW10-specific T cells from HLA-B∗57:01+/HIV+ controller and non-controller individuals. We determine the TW10-specific T cell receptor (TCR) repertoire, revealing a bias in TCR gene usage with the presence of a public TCR. We determine that the T cell response is polyfunctional regardless of the viral load, despite the low affinity of TW10-specific TCRs. We solve the crystal structure of HLA-B∗57:01-TW10 in complex with a TCR, providing the basis of recognition that underpins the strong TRBV5 bias observed in TW10-specific clonotypes
Reconsidering the Role of the Victim in Criminal Injuries Compensation
No full textNo description supplied</p
Key residues in the VDAC2-BAK complex can be targeted to modulate apoptosis
No full textAbstract: BAK and BAX execute intrinsic apoptosis by permeabilising:the mitochondrial outer membrane. Their activity is regulated through interactions with pro-survival BCL-2 family proteins and with non-BCL-2 proteins including the mitochondrial porin VDAC2. VDAC2 is important for bringing both BAK and BAX to mitochondria where they execute their apoptotic function. Despite this important function in apoptosis, while interactions with pro-survival family members are well characterised and have culminated in the development of drugs that target these interfaces to induce cancer cell apoptosis, the interaction between BAK and VDAC2 remains largely undefined. Deep scanning mutagenesis coupled with cysteine linkage identified key residues in the interaction between BAK and VDAC2. Obstructive labelling of specific residues in the BH3 domain or hydrophobic groove of BAK disrupted this interaction. Conversely, mutating specific residues in a cytosol-exposed region of VDAC2 stabilised the interaction with BAK and inhibited BAK apoptotic activity. Thus, this VDAC2–BAK interaction site can potentially be targeted to either inhibit BAK-mediated apoptosis in scenarios where excessive apoptosis contributes to disease or to promote BAK-mediated apoptosis for cancer therapy.</p
EphA3-targeted chimeric antigen receptor T cells are effective in glioma and generate curative memory T cell responses
No full textBACKGROUND: High-grade gliomas including glioblastoma (GBM) and diffuse midline gliomas (DMG) represent the most lethal and aggressive brain cancers where current treatment modalities offer limited efficacy. Chimeric antigen receptor (CAR) T cell therapies have emerged as a promising strategy, boasting tumor-specific targeting and the unique ability to penetrate the blood-brain barrier. However, the effective clinical application hinges on the optimal choice of antigen, with a limited number, currently under investigation. METHODS: We employed cell surface proteomic analysis of primary human high-grade glioma samples from both adult and pediatric patients. This led to the identification of Ephrin type-A receptor 3 (EphA3) as a prevalently expressed target. We engineered a second-generation EphA3-targeted CAR T cell and assessed function using in vitro and in vivo models of GBM and DMG. RESULTS: EphA3-targeted CAR T cells demonstrated robust antigen-specific killing of human GBM and DMG cell lines in vitro. In an orthotopic xenograft NSG mouse model, EphA3-targeted CAR T cells not only effectively eradicated tumors but also established a functional T cell population protective on rechallenge. Remarkably, mice rechallenged with a second contralateral orthotopic tumor implantation achieved complete tumor clearance and maintained a sustained complete response 6 months following initial treatment. CONCLUSION: Building on the proven safety profile of EphA3 antibodies in clinical settings, our study provides compelling preclinical evidence supporting the efficacy of EphA3-targeted CAR T cells against high-grade gliomas. These findings underscore the potential for transitioning this innovative therapy into clinical trials, aiming to revolutionize the treatment landscape for patients afflicted with these formidable brain cancers
3D-printed topological-structured electrodes with exceptional mechanical properties for high-performance flexible Li-ion batteries
No full textA vital aspect in advancing flexible batteries is the development of flexible electrodes capable of enduring repeated stretching while upholding satisfactory electrochemical performance. Thus, adopting a systematic and efficient approach to structural design and fabrication becomes imperative. In this study, we introduce an optimal structural design achieved through topology optimization and fabricate flexible electrodes via 3D printing, representing a departure from traditional design and manufacture methodologies in the development of flexible electrodes for batteries. Our research underscores the impressive mechanical strength of these topologically-structured electrodes (TSEs), validated through rigorous finite element analysis (FEA) and tensile strength testing. The results of both the stretch deformation and twist deformation analysis on the TSEs and the conventional mesh-structured electrodes (MSEs) show that the peak strain and stress of TSEs are much lower than those of MSEs. Notably, even under 50 % stretching, the TSEs maintain structural integrity, contrasting sharply with conventional mesh-structured electrodes (MSEs) and flat film electrodes which often crack under similar conditions. Moreover, after enduring 50 cycles of stretching, the TSEs retain an outstanding 98 % of their original capacity, surpassing MSEs which retain only 80 % of their capacity. These findings highlight the significant potential of topologically designed flexible electrodes, offering promising avenues for the development of stretchable and flexible energy storage devices such as wearable tech and bio-integrated electronics
Inter- and intra-athlete technique variability of conventional new ball swing bowling in elite and pre-elite Australian male fast bowlers
No full textThis study aimed to investigate inter- and intra-athlete technique variability in pre-elite and elite Australian fast bowlers delivering new ball conventional swing bowling. Ball grip angle and pelvis, torso, shoulder, elbow, wrist, upper arm, forearm, and hand kinematics were investigated at the point of ball release for inswing and outswing deliveries. Descriptive evaluations of group and individual data and k-means cluster analyses were used to assess inter- and intra-bowler technique variability. Inter-athlete technique and ball grip variability were identified, demonstrating that skilled bowlers use individualised strategies to generate swing. Functional movement variability was demonstrated by intra-athlete variability in successful swing bowling trials. Bowlers demonstrated stable technique parameters in large proximal body segments of the pelvis and torso, providing a level of repeatability to their bowling action. Greater variation was observed in bowling arm kinematics, allowing athletes to manipulate the finger and ball position to achieve the desired seam orientation at the point of ball release. This study demonstrates that skilled bowlers use individualised techniques and grips to generate swing and employ technique variations in successive deliveries. Coaches should employ individualised training strategies and use constraints-led approaches in training environments to encourage bowlers to seek adaptive movement solutions to generate swing.</p
[18]F-fluoroethyl-L-tyrosine positron emission tomography for radiotherapy target delineation: Results from a Radiation Oncology credentialing program
No full textBackground and purpose: The [18]F-fluoroethyl-L-tyrosine (FET) PET in Glioblastoma (FIG) study is an Australian prospective, multi-centre trial evaluating FET PET for newly diagnosed glioblastoma management. The Radiation Oncology credentialing program aimed to assess the feasibility in Radiation Oncologist (RO) derivation of standard-of-care target volumes (TVMR) and hybrid target volumes (TVMR+FET) incorporating pre-defined FET PET biological tumour volumes (BTVs). Materials and methods: Central review and analysis of TVMR and TVMR+FET was undertaken across three benchmarking cases. BTVs were pre-defined by a sole nuclear medicine expert. Intraclass correlation coefficient (ICC) confidence intervals (CIs) evaluated volume agreement. RO contour spatial and boundary agreement were evaluated (Dice similarity coefficient [DSC], Jaccard index [JAC], overlap volume [OV], Hausdorff distance [HD] and mean absolute surface distance [MASD]). Dose plan generation (one case per site) was assessed. Results: Data from 19 ROs across 10 trial sites (54 initial submissions, 8 resubmissions requested, 4 conditional passes) was assessed with an initial pass rate of 77.8 %; all resubmissions passed. TVMR+FET were significantly larger than TVMR (p < 0.001) for all cases. RO gross tumour volume (GTV) agreement was moderate-to-excellent for GTVMR (ICC = 0.910; 95 % CI, 0.708–0.997) and good-to-excellent for GTVMR+FET (ICC = 0.965; 95 % CI, 0.871–0.999). GTVMR+FET showed greater spatial overlap and boundary agreement compared to GTVMR. For the clinical target volume (CTV), CTVMR+FET showed lower average boundary agreement versus CTVMR (MASD: 1.73 mm vs. 1.61 mm, p = 0.042). All sites passed the planning exercise. Conclusions: The credentialing program demonstrated feasibility in successful credentialing of 19 ROs across 10 sites, increasing national expertise in TVMR+FET delineation