Abdollahi, M, Gao, X, Mei, Y, Ghosh, S, Li, J & Narag, M 2021, 'Substituting clinical features using synthetic medical phrases: Medical text data augmentation techniques', Artificial Intelligence in Medicine, vol. 120, pp. 102167-102167.
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Aboulkheyr Es, H, Bigdeli, B, Zhand, S, Aref, AR, Thiery, JP & Warkiani, ME 2021, 'Mesenchymal stem cells induce PD‐L1 expression through the secretion of CCL5 in breast cancer cells', Journal of Cellular Physiology, vol. 236, no. 5, pp. 3918-3928.
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AbstractVarious factors in the tumor microenvironment (TME) regulate the expression of PD‐L1 in cancer cells. In TME, mesenchymal stem cells (MSCs) play a crucial role in tumor progression, metastasis, and drug resistance. Emerging evidence suggests that MSCs can modulate the immune‐suppression capacity of TME through the stimulation of PD‐L1 expression in various cancers; nonetheless, their role in the induction of PD‐L1 in breast cancer remained elusive. Here, we assessed the potential of MSCs in the stimulation of PD‐L1 expression in a low PD‐L1 breast cancer cell line and explored its associated cytokine. We assessed the expression of MSCs‐related genes and their correlation with PD‐L1 across 1826 breast cancer patients from the METABRIC cohort. After culturing an ER+/differentiated/low PD‐L1 breast cancer cells with MSCs conditioned‐medium (MSC‐CM) in a microfluidic device, a variety of in‐vitro assays was carried out to determine the role of MSC‐CM in breast cancer cells' phenotype plasticity, invasion, and its effects on induction of PD‐L1 expression. In‐silico analysis showed a positive association between MSCs‐related genes and PD‐L1 expression in various types of breast cancer. Through functional assays, we revealed that MSC‐CM not only prompts a phenotype switch but also stimulates PD‐L1 expression at the protein level through secretion of various cytokines, especially CCL5. Treatment of MSCs with cytokine inhibitor pirfenidone showed a significant reduction in the secretion of CCL5 and consequently, expression of PD‐L1 in breast cancer cells. We concluded that MSCs‐derived CCL5 may act as a PD‐L1 stimulator in breast cancer.
Aghlmandi, A, Nikshad, A, Safaralizadeh, R, Warkiani, ME, Aghebati-Maleki, L & Yousefi, M 2021, 'Microfluidics as efficient technology for the isolation and characterization of stem cells.', EXCLI J, vol. 20, pp. 426-443.
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The recent years have been passed with significant progressions in the utilization of microfluidic technologies for cellular investigations. The aim of microfluidics is to mimic small-scale body environment with features like optical transparency. Microfluidics can screen and monitor different cell types during culture and study cell function in response to stimuli in a fully controlled environment. No matter how the microfluidic environment is similar to in vivo environment, it is not possible to fully investigate stem cells behavior in response to stimuli during cell proliferation and differentiation. Researchers have used stem cells in different fields from fundamental researches to clinical applications. Many cells in the body possess particular functions, but stem cells do not have a specific task and can turn into almost any type of cells. Stem cells are undifferentiated cells with the ability of changing into specific cells that can be essential for the body. Researchers and physicians are interested in stem cells to use them in testing the function of the body's systems and solving their complications. This review discusses the recent advances in utilizing microfluidic techniques for the analysis of stem cells, and mentions the advantages and disadvantages of using microfluidic technology for stem cell research.
Ahmadi, VE, Butun, I, Altay, R, Bazaz, SR, Alijani, H, Celik, S, Warkiani, ME & Koşar, A 2021, 'The effects of baffle configuration and number on inertial mixing in a curved serpentine micromixer: Experimental and numerical study', Chemical Engineering Research and Design, vol. 168, pp. 490-498.
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Recently, the application of micromixers in microfluidic systems including chemical and biological assays has been widely accomplished. Passive micromixers, benefitting from the low-cost and a less-complex fabrication process, rely solely on their geometry. In particular, Dean vortices generated in curved microchannels enhance the mixing performance through chaotic advection. To improve the mixing performance at relatively low Reynolds numbers (i.e. 1 ≤ Re ≤ 50), this study introduces baffles into the side walls of curved serpentine micromixers with curvature angles of 280°, which constantly agitate, stretch and fold the fluids streams. Six different baffle configurations were designed and the effects of geometry and the number of baffles were investigated both experimentally and numerically. According to the experimental results, while the maximum outlet mixing index of the micromixer with no baffles was 0.61, that of the micromixer with quasi-rectangular baffles was 0.98 at a low Reynolds number of 20, indicating the major contribution of the generated chaotic advection by baffles. Furthermore, numerical results, which were in good agreement with experimental results, shed more light onto the mechanisms involved in micromixing in terms of the flow behavior and mixing index.
Akar, S, Taheri, A, Bazaz, R, Warkiani, E & Shaegh, M 2021, 'Twisted architecture for enhancement of passive micromixing in a wide range of Reynolds numbers', Chemical Engineering and Processing - Process Intensification, vol. 160, pp. 108251-108251.
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Micromixers present essential roles in providing homogeneous mixtures in microfluidic systems. It is of critical importance to introduce strategies to increase the mixing efficiency of passive micromixers, capable of operating at high efficiency levels over a wide range of Reynolds (Re) numbers. To this end, a novel design of twisted microstructure for enhancing mixing performance in a wide range of Reynolds numbers was introduced. Incorporating this microstructure with straight and serpentine micromixers was numerically and experimentally investigated. Micromixers with twisted microstructures were fabricated in Poly(methyl methacrylate) (PMMA) using high-precision micromilling. The effects of Reynolds number, pitch number, and channel hydraulic diameter on mixing efficiency and pressure drop were analyzed. Results revealed that the twist architecture could increase mixing efficiency significantly with very low pressure drop of up to 0.89 kPa. The twisted serpentine micromixer could narrow the disparity of mixing efficiency from 87% (Re = 10) to 98% (Re = 400). High mixing efficiency could be achieved within a length of 4.8 mm in the twisted serpentine micromixer with a hydraulic diameter of 300 μm. Taken together, the twisted structure could be incorporated with various geometries to create compact and high efficiency micromixers for operation in a wide range of Re numbers.
Akella, A, Singh, AK, Leong, D, Lal, S, Newton, P, Clifton-Bligh, R, Mclachlan, CS, Gustin, SM, Maharaj, S, Lees, T, Cao, Z & Lin, C-T 2021, 'Classifying Multi-Level Stress Responses From Brain Cortical EEG in Nurses and Non-Health Professionals Using Machine Learning Auto Encoder', IEEE Journal of Translational Engineering in Health and Medicine, vol. 9, pp. 1-9.
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Objective
Mental stress is a major problem in our society and has become an area of interest for many psychiatric researchers. One primary research focus area is the identification of bio-markers that not only identify stress but also predict the conditions (or tasks) that cause stress. Electroencephalograms (EEGs) have been used for a long time to study and identify bio-markers. While these bio-markers have successfully predicted stress in EEG studies for binary conditions, their performance is suboptimal for multiple conditions of stress.
Methods
To overcome this challenge, we propose using latent based representations of the bio-markers, which have been shown to significantly improve EEG performance compared to traditional bio-markers alone. We evaluated three commonly used EEG based bio-markers for stress, the brain load index (BLI), the spectral power values of EEG frequency bands (alpha, beta and theta), and the relative gamma (RG), with their respective latent representations using four commonly used classifiers.
Results
The results show that spectral power value based bio-markers had a high performance with an accuracy of 83%, while the respective latent representations had an accuracy of 91%.
Alanazi, F, Gay, V, N., M & Alturki, R 2021, 'Modelling Health Process and System Requirements Engineering for Better e-Health Services in Saudi Arabia', International Journal of Advanced Computer Science and Applications, vol. 12, no. 1, pp. 549-559.
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This systematic review aimed to examine the published works on e-health modelling system requirements and suggest one applicable to Saudi Arabia. PRISMA method was adopted to search, screen and select the papers to be included in this review. Google Scholar was used as the search engine to collect relevant works. From an initial 74 works, 20 were selected after all screening procedures as per PRISMA flow diagram. The 20 selected works were discussed under various sections. The review revealed that goal setting is the first step. Using the goals, a model can be created based on which system requirements can be elicited. Different research used different approaches within this broad framework and applied the procedures to varying healthcare contexts. Based on the findings, an attempt has been made to set the goals and elicit the system requirements for a diabetes self-management model for the entire country in Saudi Arabian context. This is a preliminary model which needs to be tested, improved and then implemented.
Alharbi, AI, Gay, V, AlGhamdi, MJ, Alturki, R & Alyamani, HJ 2021, 'Towards an Application Helping to Minimize Medication Error Rate', Mobile Information Systems, vol. 2021, pp. 1-7.
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Medication errors related to medication administration done by both doctors and nurses can be considered a vital issue around the world. It is believed that systematisation and the introduction of main documents are done manually, which might increase the opportunities to have inaccuracies and errors because of unexpected wrong actions done by medical practitioners. Experts stated that the lack of pharmacological knowledge is one of the key factors, which play an important role in causing such errors. Doctors and nurses may face problems when they move from one unit to another and the medication administration list has changed. However, promoting public health activities and recent AI-enabled applications can provide general information about medication that helps both doctors and nurses administer the right medication. However, such an application can require a lot of time and effort to search and then find a medication. Therefore, this article aims to investigate whether AI-enabled applications can help avoid or at least minimize medication error rates.
Aloqaily, AA, Tafavogh, S, Harvey, BL, Catchpoole, DR & Kennedy, PJ 2021, 'Feature prioritisation on big genomic data for analysing gene-gene interactions', International Journal of Bioinformatics Research and Applications, vol. 17, no. 2, pp. 158-158.
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Complex diseases are not caused by single genes but result from intricate non-linear interactions among them. There is a critical need to implement approaches that take into account non-linear gene-gene interactions in searching for markers that jointly cause diseases. Determining the interaction between more than two single nucleotide polymorphisms (SNP) within the whole genome data is computationally expensive and often infeasible. In this paper, we develop an approach to classify patients with Acute Lymphoblastic Leukaemia by analysing multiple SNP interactions. A novel feature prioritisation algorithm called interaction effect quantity (IEQ) selects SNPs with high potential of interaction by analysing their distribution throughout the genomic data and enables deeper analysis of non-linear interactions within large datasets. We show that IEQ enables analyses of interactions between up to four SNPs, with F-measure for classification greater than 89% obtained. Such an analysis is typically much more computationally challenging if IEQ is not implemented.
Alsahafi, YA & Gay, V 2021, 'Erratum to ‘An overview of electronic personal health records’ [Health Policy and Technology 7 (2018) 427-432]', Health Policy and Technology, vol. 10, no. 4, pp. 100566-100566.
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Alzahrani, AS, Gay, V, Alturki, R & AlGhamdi, MJ 2021, 'Towards Understanding the Usability Attributes of AI-Enabled eHealth Mobile Applications', Journal of Healthcare Engineering, vol. 2021, pp. 1-8.
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Mobile application (app) use is increasingly becoming an essential part of our daily lives. Due to their significant usefulness, people rely on them to perform multiple tasks seamlessly in almost all aspects of everyday life. Similarly, there has been immense progress in artificial intelligence (AI) technology, especially deep learning, computer vision, natural language processing, and robotics. These technologies are now actively being implemented in smartphone apps and healthcare, providing multiple healthcare services. However, several factors affect the usefulness of mobile healthcare apps, and usability is an important one. There are various healthcare apps developed for each specific task, and the success of these apps depends on their performance. This study presents a systematic review of the existing apps and discusses their usability attributes. It highlights the usability models, outlines, and guidelines proposed in previous research for designing apps with improved usability characteristics. Thirty-nine research articles were reviewed and examined to identify the usability attributes, framework, and app design conducted. The results showed that satisfaction, efficiency, and learnability are the most important usability attributes to consider when designing eHealth mobile apps. Surprisingly, other significant attributes for healthcare apps, such as privacy and security, were not among the most indicated attributes in the studies.
Asano, R, Newton, PJ, Currow, DC, Macdonald, PS, Leung, D, Phillips, JL, Perrin, N & Davidson, PM 2021, 'Rationale for targeted self-management strategies for breathlessness in heart failure', Heart Failure Reviews, vol. 26, no. 1, pp. 71-79.
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To provide a conceptual rationale for targeted self-management strategies for breathlessness in chronic heart failure. Breathlessness is a defining symptom of chronic heart failure and is the primary cause for hospital readmissions and emergency room visits, resulting in extensive health care utilization. Chronic breathlessness, punctuated by acute physiological decompensation, is a sentinel symptom of the heart failure syndrome and often intensifies towards the end of life. Drawing upon evidence-based guidelines, physiological mechanisms and existing conceptual models for the management of breathlessness is proposed. Key elements of this model include adherence to evidence-based approaches (pharmacological and non-pharmacological management to optimize heart failure treatment), self-monitoring of symptoms, identification of modifiable factors (such as fluid overload), and targeted strategies for breathlessness including distraction and gas flow. Self-management is an essential component in heart failure management which could positively influences health outcomes and quality of life. Refining programs to focus on breathlessness may have the potential to reduce symptom burden and improve quality of life.
Augustine, R, Dan, P, Hasan, A, Khalaf, IM, Prasad, P, Ghosal, K, Gentile, C, McClements, L & Maureira, P 2021, 'Stem cell-based approaches in cardiac tissue engineering: controlling the microenvironment for autologous cells', Biomedicine & Pharmacotherapy, vol. 138, pp. 111425-111425.
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Azadi, S, Tafazzoli Shadpour, M & Warkiani, ME 2021, 'Characterizing the effect of substrate stiffness on the extravasation potential of breast cancer cells using a 3D microfluidic model', Biotechnology and Bioengineering, vol. 118, no. 2, pp. 823-835.
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AbstractDifferent biochemical and biomechanical cues from tumor microenvironment affect the extravasation of cancer cells to distant organs; among them, the mechanical signals are poorly understood. Although the effect of substrate stiffness on the primary migration of cancer cells has been previously probed, its role in regulating the extravasation ability of cancer cells is still vague. Herein, we used a microfluidic device to mimic the extravasation of tumor cells in a 3D microenvironment containing cancer cells, endothelial cells, and the biological matrix. The microfluidic‐based extravasation model was utilized to probe the effect of substrate stiffness on the invasion ability of breast cancer cells. MCF7 and MDA‐MB‐231 cancer cells were cultured among substrates with different stiffness which followed by monitoring their extravasation capability through the microfluidic device. Our results demonstrated that acidic collagen at a concentration of 2.5 mg/ml promotes migration of cancer cells. Additionally, the substrate softening resulted in up to 46% reduction in the invasion of breast cancer cells. The substrate softening not only affected the number of extravasated cells but also reduced their migration distance up to 53%. We further investigated the secreted level of matrix metalloproteinase 9 (MMP9) and identified that there is a positive correlation between substrate stiffening, MMP9 concentration, and extravasation of cancer cells. These findings suggest that the substrate stiffness mediates the cancer cells extravasation in a microfluidic model. Changes in MMP9 level could be one of the possible underlying mechanisms which need more investigations to be addressed thoroughly.
Bakirov, R, Fay, D & Gabrys, B 2021, 'Automated adaptation strategies for stream learning', Machine Learning, vol. 110, no. 6, pp. 1429-1462.
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AbstractAutomation of machine learning model development is increasingly becoming an established research area. While automated model selection and automated data pre-processing have been studied in depth, there is, however, a gap concerning automated model adaptation strategies when multiple strategies are available. Manually developing an adaptation strategy can be time consuming and costly. In this paper we address this issue by proposing the use of flexible adaptive mechanism deployment for automated development of adaptation strategies. Experimental results after using the proposed strategies with five adaptive algorithms on 36 datasets confirm their viability. These strategies achieve better or comparable performance to the custom adaptation strategies and the repeated deployment of any single adaptive mechanism.
Banerjee, S, Lyu, J, Huang, Z, Leung, HFF, Lee, TT-Y, Yang, D, Su, S, Zheng, Y & Ling, S-H 2021, 'Light-Convolution Dense Selection U-Net (LDS U-Net) for Ultrasound Lateral Bony Feature Segmentation', Applied Sciences, vol. 11, no. 21, pp. 10180-10180.
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Scoliosis is a widespread medical condition where the spine becomes severely deformed and bends over time. It mostly affects young adults and may have a permanent impact on them. A periodic assessment, using a suitable modality, is necessary for its early detection. Conventionally, the usually employed modalities include X-ray and MRI, which employ ionising radiation and are expensive. Hence, a non-radiating 3D ultrasound imaging technique has been developed as a safe and economic alternative. However, ultrasound produces low-contrast images that are full of speckle noise, and skilled intervention is necessary for their processing. Given the prevalent occurrence of scoliosis and the limitations of scalability of human expert interventions, an automatic, fast, and low-computation assessment technique is being developed for mass scoliosis diagnosis. In this paper, a novel hybridized light-weight convolutional neural network architecture is presented for automatic lateral bony feature identification, which can help to develop a fully-fledged automatic scoliosis detection system. The proposed architecture, Light-convolution Dense Selection U-Net (LDS U-Net), can accurately segment ultrasound spine lateral bony features, from noisy images, thanks to its capabilities of smartly selecting only the useful information and extracting rich deep layer features from the input image. The proposed model is tested using a dataset of 109 spine ultrasound images. The segmentation result of the proposed network is compared with basic U-Net, Attention U-Net, and MultiResUNet using various popular segmentation indices. The results show that LDS U-Net provides a better segmentation performance compared to the other models. Additionally, LDS U-Net requires a smaller number of parameters and less memory, making it suitable for a large-batch screening process of scoliosis without a high computational requirement.
Basirun, C, Ferlazzo, ML, Howell, NR, Liu, G-J, Middleton, RJ, Martinac, B, Narayanan, SA, Poole, K, Gentile, C & Chou, J 2021, 'Microgravity × Radiation: A Space Mechanobiology Approach Toward Cardiovascular Function and Disease', Frontiers in Cell and Developmental Biology, vol. 9, p. 750775.
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In recent years, there has been an increasing interest in space exploration, supported by the accelerated technological advancements in the field. This has led to a new potential environment that humans could be exposed to in the very near future, and therefore an increasing request to evaluate the impact this may have on our body, including health risks associated with this endeavor. A critical component in regulating the human pathophysiology is represented by the cardiovascular system, which may be heavily affected in these extreme environments of microgravity and radiation. This mini review aims to identify the impact of microgravity and radiation on the cardiovascular system. Being able to understand the effect that comes with deep space explorations, including that of microgravity and space radiation, may also allow us to get a deeper understanding of the heart and ultimately our own basic physiological processes. This information may unlock new factors to consider with space exploration whilst simultaneously increasing our knowledge of the cardiovascular system and potentially associated diseases.
Bliuc, D, Tran, T, Adachi, JD, Atkins, GJ, Berger, C, van den Bergh, J, Cappai, R, Eisman, JA, van Geel, T, Geusens, P, Goltzman, D, Hanley, DA, Josse, R, Kaiser, S, Kovacs, CS, Langsetmo, L, Prior, JC, Nguyen, TV, Solomon, LB, Stapledon, C & Center, JR 2021, 'Cognitive decline is associated with an accelerated rate of bone loss and increased fracture risk in women: a prospective study from the Canadian Multicentre Osteoporosis Study', Journal of Bone and Mineral Research, vol. 36, no. 11, pp. 2106-2115.
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ABSTRACT Cognitive decline and osteoporosis often coexist and some evidence suggests a causal link. However, there are no data on the longitudinal relationship between cognitive decline, bone loss and fracture risk, independent of aging. This study aimed to determine the association between: (i) cognitive decline and bone loss; and (ii) clinically significant cognitive decline (≥3 points) on Mini Mental State Examination (MMSE) over the first 5 years and subsequent fracture risk over the following 10 years. A total of 1741 women and 620 men aged ≥65 years from the population-based Canadian Multicentre Osteoporosis Study were followed from 1997 to 2013. Association between cognitive decline and (i) bone loss was estimated using mixed-effects models; and (ii) fracture risk was estimated using adjusted Cox models. Over 95% of participants had normal cognition at baseline (MMSE ≥ 24). The annual % change in MMSE was similar for both genders (women −0.33, interquartile range [IQR] −0.70 to +0.00; and men −0.34, IQR: −0.99 to 0.01). After multivariable adjustment, cognitive decline was associated with bone loss in women (6.5%; 95% confidence interval [CI], 3.2% to 9.9% for each percent decline in MMSE from baseline) but not men. Approximately 13% of participants experienced significant cognitive decline by year 5. In women, fracture risk was increased significantly (multivariable hazard ratio [HR], 1.61; 95% CI, 1.11 to 2.34). There were too few men to analyze. There was a significant association between cognitive decline and both bone loss and fracture risk, independent of aging, in women. Further studies are needed to determine mechanisms that link these common conditions. © 2021 American Society for Bone and Mineral Research (ASBMR).
Bousquet, J, Anto, JM, Czarlewski, W, Haahtela, T, Fonseca, SC, Iaccarino, G, Blain, H, Vidal, A, Sheikh, A, Akdis, CA & Zuberbier, T 2021, 'Cabbage and fermented vegetables: From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID‐19', Allergy, vol. 76, no. 3, pp. 735-750.
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AbstractLarge differences in COVID‐19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS‐CoV‐2 binds to its receptor, the angiotensin‐converting enzyme 2 (ACE2). As a result of SARS‐CoV‐2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID‐19. The nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT1R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof‐of‐concept of dietary manipulations that may enhance Nrf2‐associated antioxidant effects, helpful in mitigating COVID‐19 severity.
Bradbury, P, Nader, CP, Cidem, A, Rutting, S, Sylvester, D, He, P, Rezcallah, MC, O’Neill, GM & Ammit, AJ 2021, 'Tropomyosin 2.1 collaborates with fibronectin to promote TGF-β1-induced contraction of human lung fibroblasts', Respiratory Research, vol. 22, no. 1, pp. 1-10.
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AbstractMany lung diseases are characterized by fibrosis, leading to impaired tissue patency and reduced lung function. Development of fibrotic tissue depends on two-way interaction between the cells and the extra-cellular matrix (ECM). Concentration-dependent increased stiffening of the ECM is sensed by the cells, which in turn increases intracellular contraction and pulling on the matrix causing matrix reorganization and further stiffening. It is generally accepted that the inflammatory cytokine growth factor β1 (TGF-β1) is a major driver of lung fibrosis through the stimulation of ECM production. However, TGF-β1 also regulates the expression of members of the tropomyosin (Tm) family of actin associating proteins that mediate ECM reorganization through intracellular-generated forces. Thus, TGF-β1 may mediate the bi-directional signaling between cells and the ECM that promotes tissue fibrosis. Using combinations of cytokine stimulation, mRNA, protein profiling and cellular contractility assays with human lung fibroblasts, we show that concomitant induction of key Tm isoforms and ECM by TGF-β1, significantly accelerates fibrotic phenotypes. Knocking down Tpm2.1 reduces fibroblast-mediated collagen gel contraction. Collectively, the data suggest combined ECM secretion and actin cytoskeleton contractility primes the tissue for enhanced fibrosis. Our study suggests that Tms are at the nexus of inflammation and tissue stiffening. Small molecules targeting specific Tm isoforms have recently been designed; thus targeting Tpm2.1 may represent a novel therapeutic target in lung fibrosis.
Brzozowska, MM, Tran, T, Bliuc, D, Jorgensen, J, Talbot, M, Fenton-Lee, D, Chen, W, Hong, A, Viardot, A, White, CP, Nguyen, TV, Pocock, N, Eisman, JA, Baldock, PA & Center, JR 2021, 'Roux-en-Y gastric bypass and gastric sleeve surgery result in long term bone loss', International Journal of Obesity, vol. 45, no. 1, pp. 235-246.
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Objectives
Little is known about the long-term skeletal impact of bariatric procedures, particularly the increasingly commonly performed gastric sleeve surgery (GS). We examined bone density (BMD) change following three types of bariatric surgery Roux-en-Y gastric bypass (RYGB), GS and laparoscopic adjustable gastric banding (LAGB), compared with diet, over 36 months.
Methods
Non-randomized, prospective study of participants with severe obesity (n = 52), undergoing weight-loss interventions: RYGB (n = 7), GS (n = 21), LAGB (n = 11) and diet (n = 13). Measurements of calciotropic indices, gut hormones (fasting and post prandial) peptide YY (PYY), glucagon-like peptide 1 (GLP1) and adiponectin together with dual-X-ray absorptiometry and quantitative computed tomography scans were performed thorough the study.
Results
All groups lost weight during the first 12 months. Despite weight stability from 12 to 36 months and supplementation of calcium and vitamin D, there was progressive bone loss at the total hip (TH) over 36 months in RYGB -14% (95% CI: -12, -17) and GS -9% (95% CI: -7, -10). In RYGB forearm BMD also declined over 36 months -9% (95% CI: -6, -12) and LS BMD declined over the first 12 months -7% (95% CI: -3, -12). RYGB and GS groups experienced significantly greater bone loss until 36 months than LAGB and diet groups, which experienced no significant BMD loss. These bone losses remained significant after adjustment for weight loss and age. RYGB and GS procedures resulted in elevated postprandial PYY, adiponectin and bone turnover markers up to 36 months without such changes among LAGB and diet participants.
Conclusions
RYGB and GS but not LAGB resulted in ongoing TH bone loss for three postoperative years. For RYGB, bone loss was also observed at LS and non-weight-bearing forearms. These BMD changes were independent of weight and age differences. We, therefore, recommend close monitoring of bone health following RYGB a...
Budati, AK & Ling, SSH 2021, 'Guest editorial: Machine Learning in Wireless Networks.', CAAI Trans. Intell. Technol., vol. 6, no. 2, pp. 133-134.
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Bulsara, SM, Wainberg, ML, Rogers, K, McAloon, J, Grove, R & Newton-John, TRO 2021, 'The Role of Comorbidity on Retention in HIV Care', AIDS and Behavior, vol. 25, no. 5, pp. 1532-1541.
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Retention is a central component of the Cascade, facilitating monitoring of comorbidity. Country-specific definitions differ and may suit stable and functioning clients, while not appropriately classifying complex clinical presentations characterized by comorbidity. A retrospective file review of 363 people living with HIV attending a Sydney HIV clinic was conducted. Retention was compared with Australian (attendance once/12-months) and World Health Organization (attendance 'appropriate to need') recommendations to identify those attending according to the Australian definition, but not clinician recommendations (AUnotWHO). Multivariable logistic regression analyses determined the impact of age/sex and clinician-assessed comorbidity on retention. Most (97%) participants were considered retained according to the Australian definition, but only 56.7% according to clinician recommendations. Those with psychosocial comorbidity alone were less likely to be in the AUnotWHO group (OR 0.51, 95%CI 0.27-0.96, p = 0.04). The interaction of physical and psychosocial comorbidity was predictive of poor retention (Wald test: χ2 = 6.39, OR 2.39 [95% CI 1.15-4.97], p = 0.01), suggesting a syndemic relationship.
Cahill, PJ, Lobb, EA, Sanderson, CR & Phillips, JL 2021, 'Patients Receiving Palliative Care and Their Families' Experiences of Participating in a “Patient-Centered Family Meeting”: A Qualitative Substudy of the Valuing Opinions, Individual Communication, and Experience Feasibility Trial', Palliative Medicine Reports, vol. 2, no. 1, pp. 305-315.
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Cai, X, Li, JJ, Liu, T, Brian, O & Li, J 2021, 'Infectious disease mRNA vaccines and a review on epitope prediction for vaccine design', Briefings in Functional Genomics, vol. 20, no. 5, pp. 289-303.
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AbstractMessenger RNA (mRNA) vaccines have recently emerged as a new type of vaccine technology, showing strong potential to combat the COVID-19 pandemic. In addition to SARS-CoV-2 which caused the pandemic, mRNA vaccines have been developed and tested to prevent infectious diseases caused by other viruses such as Zika virus, the dengue virus, the respiratory syncytial virus, influenza H7N9 and Flavivirus. Interestingly, mRNA vaccines may also be useful for preventing non-infectious diseases such as diabetes and cancer. This review summarises the current progresses of mRNA vaccines designed for a range of diseases including COVID-19. As epitope study is a primary component in the in silico design of mRNA vaccines, we also survey on advanced bioinformatics and machine learning algorithms which have been used for epitope prediction, and review on user-friendly software tools available for this purpose. Finally, we discuss some of the unanswered concerns about mRNA vaccines, such as unknown long-term side effects, and present with our perspectives on future developments in this exciting area.
Camaya, I, Mok, TY, Lund, M, To, J, Braidy, N, Robinson, MW, Santos, J, O’Brien, B & Donnelly, S 2021, 'The parasite-derived peptide FhHDM-1 activates the PI3K/Akt pathway to prevent cytokine-induced apoptosis of β-cells', Journal of Molecular Medicine, vol. 99, no. 11, pp. 1605-1621.
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Type 1 diabetes (T1D) is an autoimmune disease characterised by the destruction of the insulin-producing beta (β)-cells within the pancreatic islets. We have previously identified a novel parasite-derived molecule, termed Fasciola hepatica helminth defence molecule 1 (FhHDM-1), that prevents T1D development in non-obese diabetic (NOD) mice. In this study, proteomic analyses of pancreas tissue from NOD mice suggested that FhHDM-1 activated the PI3K/Akt signalling pathway, which is associated with β-cell metabolism, survival and proliferation. Consistent with this finding, FhHDM-1 preserved β-cell mass in NOD mice. Examination of the biodistribution of FhHDM-1 after intraperitoneal administration in NOD mice revealed that the parasite peptide localised to the pancreas, suggesting that it exerted a direct effect on the survival/function of β-cells. This was confirmed in vitro, as the interaction of FhHDM-1 with the NOD-derived β-cell line, NIT-1, resulted in increased levels of phosphorylated Akt, increased NADH and NADPH and reduced activity of the NAD-dependent DNA nick sensor, poly(ADP-ribose) polymerase (PARP-1). As a consequence, β-cell survival was enhanced and apoptosis was prevented in the presence of the pro-inflammatory cytokines that destroy β-cells during T1D pathogenesis. Similarly, FhHDM-1 protected primary human islets from cytokine-induced apoptosis. Importantly, while FhHDM-1 promoted β-cell survival, it did not induce proliferation. Collectively, these data indicate that FhHDM-1 has significant therapeutic applications to promote β-cell survival, which is required for T1D and T2D prevention and islet transplantation. KEY MESSAGES: FhHDM-1 preserves β-cell mass in NOD mice and prevents the development of T1D. FhHDM-1 enhances phosphorylation of Akt in mouse β-cell lines. FhHDM-1 increases levels of NADH/NADPH in mouse β-cell lines in vitro. FhHDM-1 prevents cytokine-induced cell death of mouse β-cell lines and primary human β-cells in vitr...
Cao, Z, John, AR, Chen, H-T, Martens, KE, Georgiades, M, Gilat, M, Nguyen, HT, Lewis, SJG & Lin, C-T 2021, 'Identification of EEG Dynamics During Freezing of Gait and Voluntary Stopping in Patients With Parkinson’s Disease', IEEE Transactions on Neural Systems and Rehabilitation Engineering, vol. 29, pp. 1774-1783.
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Mobility is severely impacted in patients with Parkinson's disease (PD), who often experience involuntary stopping from the freezing of gait (FOG). Understanding the neurophysiological difference between “voluntary stopping” and “involuntary stopping” caused by FOG is vital for the detection of and potential intervention for FOG in the daily lives of patients. This study characterised the electroencephalographic (EEG) signature associated with FOG in contrast to voluntary stopping. The protocol consisted of a timed up-and-go (TUG) task and an additional TUG task with a voluntary stopping component, where participants reacted to verbal “stop” and “walk” instructions by voluntarily stopping or walking. Event-related spectral perturbation (ERSP) analysis was performed to study the dynamics of the EEG spectra induced by different walking phases, including normal walking, voluntary stopping and episodes of involuntary stopping (FOG), as well as the transition windows between normal walking and voluntary stopping or FOG. These results demonstrate for the first time that the EEG signal during the transition from walking to voluntary stopping is distinguishable from that during the transition to involuntary stopping caused by FOG. The EEG signature of voluntary stopping exhibits a significantly decreased power spectrum compared with that of FOG episodes, with distinctly different patterns in the delta and low-beta power in the central area. These findings suggest the possibility of a practical EEG-based tool that can accurately predict FOG episodes, excluding the potential confounding of voluntary stopping.
Cerdan Chiscano, M & Darcy, S 2021, 'C2C co-creation of inclusive tourism experiences for customers with disability in a shared heritage context experience', Current Issues in Tourism, vol. 24, no. 21, pp. 3072-3089.
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This study explores customer-to-customer (C2C) social co-creation practices in tourism when customers with and without disability share a heritage service environment. Despite a growing prevalence of heritage- and disability-related research in the tourism literature, few scholars have examined the phenomena from the emergent customer-dominant logic (CDL) perspective. This study makes empirical use of the perceptions of customers with disabilities (CwD) in a recent process of co-creation of CDL within the context of heritage sites through qualitative ethnographic techniques, interviews and observation methods. A sample of 125 individuals with and without disabilities participated in the fieldwork. The objective was to identify C2C social practices that occur among CwD and their related value, leading to either inclusion or exclusion. The results reveal the importance of focusing on C2C co-creation opportunities which create a value outcome. This paper provides heritage managers with clear guidance for creating inclusive and enabling servicescapes.
Chai, M, Razavi Bazaz, S, Daiyan, R, Razmjou, A, Ebrahimi Warkiani, M, Amal, R & Chen, V 2021, 'Biocatalytic micromixer coated with enzyme-MOF thin film for CO2 conversion to formic acid', Chemical Engineering Journal, vol. 426, pp. 130856-130856.
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In this study, a novel micromixer with a 3D helical, threaded channel was fabricated via 3D printing. The micromixer can enhance the mass transfer of reactants and product in an enzymatic cascade reaction converting CO2 to formic acid. Two enzymes, including carbonic anhydrase (CA) and formate dehydrogenase (FDH), were biomineralised in a zeolitic imidazolate framework-8 composite thin film on the micromixer channel that has been modified with polydopamine/polyethyleneimine. The biocatalytic performance of the micromixer was evaluated by testing at various liquid flow rates, and an optimum liquid flow rate at 1 mL/min (Rel = 8, Del = 3) was observed as the two-phase flow pattern in the micromixer channel transitioned from slug flow to bubbly flow. A comparison of the micromixer performance with and without threaded channels revealed ~ 170% enhancement in formic acid yield, indicating improved mixing with the presence of threads. In addition, the formic acid production rate for the micromixer with threaded channel was three folds higher than a conventional bubble column, demonstrating the superior performance of the proposed micromixer. The ease of assembling multiple micromixer units in series also enabled the immobilisation of different enzymes in separate units to carry out sequential reactions in a modular system. As a proof of concept, the solution product collected from long term biocatalysis was also tested in a direct formic acid fuel cell, which showed a promising prospect of integrating these two systems for a closed-loop energy generation system.
Chan, Y, Ng, SW, Singh, SK, Gulati, M, Gupta, G, Chaudhary, SK, Hing, GB, Collet, T, MacLoughlin, R, Löbenberg, R, Oliver, BG, Chellappan, DK & Dua, K 2021, 'Revolutionizing polymer-based nanoparticle-linked vaccines for targeting respiratory viruses: A perspective', Life Sciences, vol. 280, pp. 119744-119744.
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Viral respiratory tract infections have significantly impacted global health as well as socio-economic growth. Respiratory viruses such as the influenza virus, respiratory syncytial virus (RSV), and the recent SARS-CoV-2 infection (COVID-19) typically infect the upper respiratory tract by entry through the respiratory mucosa before reaching the lower respiratory tract, resulting in respiratory disease. Generally, vaccination is the primary method in preventing virus pathogenicity and it has been shown to remarkably reduce the burden of various infectious diseases. Nevertheless, the efficacy of conventional vaccines may be hindered by certain limitations, prompting the need to develop novel vaccine delivery vehicles to immunize against various strains of respiratory viruses and to mitigate the risk of a pandemic. In this review, we provide an insight into how polymer-based nanoparticles can be integrated with the development of vaccines to effectively enhance immune responses for combating viral respiratory tract infections.
Chan, Y, Prasher, P, Löbenberg, R, Gupta, G, Singh, SK, Oliver, BG, Chellappan, DK & Dua, K 2021, 'Applications and practice of advanced drug delivery systems for targeting Toll-like receptors in pulmonary diseases', Nanomedicine, vol. 16, no. 10, pp. 783-786.
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Chellappan, DK, Dharwal, V, Paudel, KR, Jha, NK, MacLoughlin, R, Oliver, BG, M Hansbro, P & Dua, K 2021, 'Mitochondrial dysfunctions associated with chronic respiratory diseases and their targeted therapies: an update', Future Medicinal Chemistry, vol. 13, no. 15, pp. 1249-1251.
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Chen, H, Chhor, M, Rayner, BS, McGrath, K & McClements, L 2021, 'Evaluation of the diagnostic accuracy of current biomarkers in heart failure with preserved ejection fraction: A systematic review and meta-analysis', Archives of Cardiovascular Diseases, vol. 114, no. 12, pp. 793-804.
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Background: A number of circulating biomarkers are currently utilized for the diagnosis of chronic heart failure with preserved ejection fraction (HFpEF). However, due to HFpEF heterogeneity, the accuracy of these biomarkers remains unclear. Aims: This study aimed to systematically determine the diagnostic accuracy of currently available biomarkers for chronic HFpEF. Methods: PubMed, Web of Science, MEDLINE and SCOPUS databases were searched systematically to identify studies assessing the diagnostic accuracy of biomarkers of chronic HFpEF with left ventricular ejection fraction (LVEF) ≥ 50%. All included studies were independently assessed for quality and relevant information was extracted. Random-effects models were used to estimate the pooled diagnostic accuracy of HFpEF biomarkers. Results: The search identified 6145 studies, of which 19 were included. Four biomarkers were available for meta-analysis. The pooled sensitivity of B-type natriuretic peptide (BNP) (0.787, 95% confidence interval [CI] 0.719–0.842) was higher than that of N-terminal pro-BNP (NT-proBNP) (0.696, 95% CI 0.599–0.779) in chronic HFpEF diagnosis. However, NT-proBNP showed improved specificity (0.882, 95% CI 0.778–0.941) compared to BNP (\0.796, 95% CI 0.672–0.882). Galectin-3 (Gal-3) exhibited a reliable diagnostic adequacy for HFpEF (sensitivity 0.760, 95% CI 0.631–0.855; specificity 0.803, 95% CI 0.667–0.893). However, suppression of tumorigenesis-2 (ST2) displayed limited diagnostic performance for chronic HFpEF diagnosis (sensitivity 0.636, 95% CI 0.465–0.779; specificity 0.595, 95% CI 0.427–0.743). Conclusion: NT-proBNP and BNP appear to be the most reliable biomarkers in chronic HFpEF with NT-proBNP showing higher specificity and BNP showing higher sensitivity. Although Gal-3 appears more reliable than ST2 in HFpEF diagnosis, the conclusions are limited as only three studies were included in this meta-analysis.
Chen, H, Lin, Y, Chen, Y, Chen, S, Nassif, N & McGowan, E 2021, 'P-86 The importance of sphingosine kinase 1 isoform expression in the gut-liver axis', Annals of Oncology, vol. 32, pp. S127-S127.
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Chen, H, Wang, B, Li, G, Steele, JR, Stayte, S, Vissel, B, Chan, YL, Yi, C, Saad, S, Machaalani, R & Oliver, BG 2021, 'Brain health is independently impaired by E-vaping and high-fat diet', Brain, Behavior, and Immunity, vol. 92, pp. 57-66.
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Tobacco smoking and high-fat diet (HFD) independently impair short-term memory. E-cigarettes produce e-vapour containing flavourings and nicotine. Here, we investigated whether e-vapour inhalation interacts with HFD to affect short-term memory and neural integrity. Balb/c mice (7 weeks, male) were fed a HFD (43% fat, 20 kJ/g) for 16 weeks. In the last 6 weeks, half of the mice were exposed to tobacco-flavoured e-vapour from nicotine-containing (18 mg/L) or nicotine-free (0 mg/L) e-fluids twice daily. Short-term memory function was measured in week 15. HFD alone did not impair memory function, but increased brain phosphorylated (p)-Tau and astrogliosis marker, while neuron and microglia levels were decreased. E-vapour exposure significantly impaired short-term memory function independent of diet and nicotine. Nicotine free e-vapour induced greater changes compared to the nicotine e-vapour and included, increased systemic cytokines, increased brain p-Tau and decreased postsynaptic density protein (PSD)-95 levels in chow-fed mice, and decreased astrogliosis marker, increased microglia and increased glycogen synthase kinase levels in HFD-fed mice. Increased hippocampal apoptosis was also differentially observed in chow and HFD mice. In conclusion, E-vapour exposure impaired short-term memory independent of diet and nicotine, and was correlated to increased systemic inflammation, reduced PSD-95 level and increased astrogliosis in chow-fed mice, but decreased gliosis and increased microglia in HFD-fed mice, indicating the inflammatory nature of e-vapour leading to short term memory impairment.
Chen, J, Nelson, C, Wong, M, Tee, AE, Liu, PY, La, T, Fletcher, JI, Kamili, A, Mayoh, C, Bartenhagen, C, Trahair, TN, Xu, N, Jayatilleke, N, Wong, M, Peng, H, Atmadibrata, B, Cheung, BB, Lan, Q, Bryan, TM, Mestdagh, P, Vandesompele, J, Combaret, V, Boeva, V, Wang, JY, Janoueix-Lerosey, I, Cowley, MJ, MacKenzie, KL, Dolnikov, A, Li, J, Polly, P, Marshall, GM, Reddel, RR, Norris, MD, Haber, M, Fischer, M, Zhang, XD, Pickett, HA & Liu, T 2021, 'Targeted Therapy of TERT-Rearranged Neuroblastoma with BET Bromodomain Inhibitor and Proteasome Inhibitor Combination Therapy', Clinical Cancer Research, vol. 27, no. 5, pp. 1438-1451.
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Abstract Purpose: TERT gene rearrangement with transcriptional superenhancers leads to TERT overexpression and neuroblastoma. No targeted therapy is available for clinical trials in patients with TERT-rearranged neuroblastoma. Experimental Design: Anticancer agents exerting the best synergistic anticancer effects with BET bromodomain inhibitors were identified by screening an FDA-approved oncology drug library. The synergistic effects of the BET bromodomain inhibitor OTX015 and the proteasome inhibitor carfilzomib were examined by immunoblot and flow cytometry analysis. The anticancer efficacy of OTX015 and carfilzomib combination therapy was investigated in mice xenografted with TERT-rearranged neuroblastoma cell lines or patient-derived xenograft (PDX) tumor cells, and the role of TERT reduction in the anticancer efficacy was examined through rescue experiments in mice. Results: The BET bromodomain protein BRD4 promoted TERT-rearranged neuroblastoma cell proliferation through upregulating TERT expression. Screening of an approved oncology drug library identified the proteasome inhibitor carfilzomib as the agent exerting the best synergistic anticancer effects with BET bromodomain inhibitors including OTX015. OTX015 and carfilzomib synergistically reduced TERT protein expression, induced endoplasmic reticulum stress, and induced TERT-rearranged neuroblastoma cell apoptosis which was blocked by TERT overexpression and endoplasmic reticulum stress antagonists. In mice xenografted with TERT-rearranged neuroblastoma cell lines or PDX tumor cells, OTX015 and carfilzomib synergistica...
Chen, S-Y, Beretta, M, Alexopoulos, SJ, Shah, DP, Olzomer, EM, Hargett, SR, Childress, ES, Salamoun, JM, Aleksovska, I, Roseblade, A, Cranfield, C, Rawling, T, Quinlan, KGR, Morris, MJ, Tucker, SP, Santos, WL & Hoehn, KL 2021, 'Mitochondrial uncoupler SHC517 reverses obesity in mice without affecting food intake', Metabolism, vol. 117, pp. 154724-154724.
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Aims
Mitochondrial uncouplers decrease caloric efficiency and have potential therapeutic benefits for the treatment of obesity and related metabolic disorders. Herein we investigate the metabolic and physiologic effects of a recently identified small molecule mitochondrial uncoupler named SHC517 in a mouse model of diet-induced obesity.
Methods
SHC517 was administered as an admixture in food. The effect of SHC517 on in vivo energy expenditure and respiratory quotient was determined by indirect calorimetry. A dose-finding obesity prevention study was performed by starting SHC517 treatment concomitant with high fat diet for a period of 12 days. An obesity reversal study was performed by feeding mice western diet for 4 weeks prior to SHC517 treatment for 7 weeks. Biochemical assays were used to determine changes in glucose, insulin, triglycerides, and cholesterol. SHC517 concentrations were determined by mass spectrometry.
Results
SHC517 increased lipid oxidation without affecting body temperature. SHC517 prevented diet-induced obesity when administered at 0.05% and 0.1% w/w in high fat diet and reversed established obesity when tested at the 0.05% dose. In the obesity reversal model, SHC517 restored adiposity to levels similar to chow-fed control mice without affecting food intake or lean body mass. SHC517 improved glucose tolerance and fasting glucose levels when administered in both the obesity prevention and obesity reversal modes.
Conclusions
SHC517 is a mitochondrial uncoupler with potent anti-obesity and insulin sensitizing effects in mice. SHC517 reversed obesity without altering food intake or compromising lean mass, effects that are highly sought-after in anti-obesity therapeutics.
Cheung, BB, Kleynhans, A, Mittra, R, Kim, PY, Holien, JK, Nagy, Z, Ciampa, OC, Seneviratne, JA, Mayoh, C, Raipuria, M, Gadde, S, Massudi, H, Wong, IPL, Tan, O, Gong, A, Suryano, A, Diakiw, SM, Liu, B, Arndt, GM, Liu, T, Kumar, N, Sangfelt, O, Zhu, S, Norris, MD, Haber, M, Carter, DR, Parker, MW & Marshall, GM 2021, 'A novel combination therapy targeting ubiquitin-specific protease 5 in MYCN-driven neuroblastoma', Oncogene, vol. 40, no. 13, pp. 2367-2381.
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AbstractHistone deacetylase (HDAC) inhibitors are effective in MYCN-driven cancers, because of a unique need for HDAC recruitment by the MYCN oncogenic signal. However, HDAC inhibitors are much more effective in combination with other anti-cancer agents. To identify novel compounds which act synergistically with HDAC inhibitor, such as suberanoyl hydroxamic acid (SAHA), we performed a cell-based, high-throughput drug screen of 10,560 small molecule compounds from a drug-like diversity library and identified a small molecule compound (SE486-11) which synergistically enhanced the cytotoxic effects of SAHA. Effects of drug combinations on cell viability, proliferation, apoptosis and colony forming were assessed in a panel of neuroblastoma cell lines. Treatment with SAHA and SE486-11 increased MYCN ubiquitination and degradation, and markedly inhibited tumorigenesis in neuroblastoma xenografts, and, MYCN transgenic zebrafish and mice. The combination reduced ubiquitin-specific protease 5 (USP5) levels and increased unanchored polyubiquitin chains. Overexpression of USP5 rescued neuroblastoma cells from the cytopathic effects of the combination and reduced unanchored polyubiquitin, suggesting USP5 is a therapeutic target of the combination. SAHA and SE486-11 directly bound to USP5 and the drug combination exhibited a 100-fold higher binding to USP5 than individual drugs alone in microscale thermophoresis assays. MYCN bound to the USP5 promoter and induced USP5 gene expression suggesting that USP5 and MYCN expression created a forward positive feedback loop in neuroblastoma cells. Thus, USP5 acts as an oncogenic cofactor with MYCN in neuroblastoma and the novel combination of HDAC inhibitor with SE486-11 represents a novel therapeutic approach for the treatment of MYCN-driven neuroblastoma.
Cohen, R, Newton-John, T & Slater, A 2021, 'The case for body positivity on social media: Perspectives on current advances and future directions', Journal of Health Psychology, vol. 26, no. 13, pp. 2365-2373.
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In recent years, the body-positive movement has emerged on social media and has generated both support and criticism in pop-cultural discourse. We review the potential benefits and disadvantages of ‘body positivity’ on social media in light of theory and the available research. Based on the early evidence showing potential benefits of engaging with body-positive content on social media for positive body image, a case is made in support of this emerging content. Nevertheless, recommendations are made for future research with an emphasis on experimental and longitudinal investigations of actual health outcomes of engaging with body positivity on social media and clarification of the potential relationship between body positivity and objectification.
Coignard, J, Lush, M, Beesley, J, O’Mara, TA, Dennis, J, Tyrer, JP, Barnes, DR, McGuffog, L, Leslie, G, Bolla, MK, Adank, MA, Agata, S, Ahearn, T, Aittomäki, K, Andrulis, IL, Anton-Culver, H, Arndt, V, Arnold, N, Aronson, KJ, Arun, BK, Augustinsson, A, Azzollini, J, Barrowdale, D, Baynes, C, Becher, H, Bermisheva, M, Bernstein, L, Białkowska, K, Blomqvist, C, Bojesen, SE, Bonanni, B, Borg, A, Brauch, H, Brenner, H, Burwinkel, B, Buys, SS, Caldés, T, Caligo, MA, Campa, D, Carter, BD, Castelao, JE, Chang-Claude, J, Chanock, SJ, Chung, WK, Claes, KBM, Clarke, CL, Bertrand, O, Caputo, S, Dupré, A, Le Mentec, M, Belotti, M, Birot, A-M, Buecher, B, Fourme, E, Gauthier-Villars, M, Golmard, L, Houdayer, C, Moncoutier, V, de Pauw, A, Saule, C, Sinilnikova, O, Mazoyer, S, Damiola, F, Barjhoux, L, Verny-Pierre, C, Léone, M, Boutry-Kryza, N, Calender, A, Giraud, S, Caron, O, Guillaud-Bataille, M, Bressac-de-Paillerets, B, Bignon, Y-J, Uhrhammer, N, Lasset, C, Bonadona, V, Berthet, P, Vaur, D, Castera, L, Noguchi, T, Popovici, C, Sobol, H, Bourdon, V, Noguchi, T, Remenieras, A, Noguès, C, Coupier, I, Pujol, P, Dumont, A, Révillion, F, Adenis, C, Muller, D, Barouk-Simonet, E, Bonnet, F, Bubien, V, Sevenet, N, Longy, M, Toulas, C, Guimbaud, R, Gladieff, L, Feillel, V, Leroux, D, Dreyfus, H, Rebischung, C, Peysselon, M, Coron, F, Faivre, L, Baurand, A, Jacquot, C, Bertolone, G, Lizard, S, Prieur, F, Lebrun, M, Kientz, C, Ferrer, SF, Mari, V, Vénat-Bouvet, L, Delnatte, C, Bézieau, S, Mortemousque, I, Coulet, F, Colas, C, Soubrier, F, Warcoin, M, Sokolowska, J, Bronner, M, Collonge-Rame, M-A, Damette, A, Gesta, P, Lallaoui, H, Chiesa, J, Molina-Gomes, D, Ingster, O, Gregory, H, Miedzybrodzka, Z, Morrison, PJ, Ong, K-R, Donaldson, A, Rogers, MT, Kennedy, MJ, Porteous, ME, Brewer, C, Davidson, R, Izatt, L, Brady, A, Barwell, J, Adlard, J, Foo, C, Lalloo, F, Side, LE, Eason, J, Henderson, A, Walker, L, Eeles, RA, Cook, J, Snape, K, Eccles, D, Murray, A, McCann, E, Collée, JM, Conroy, DM, Czene, K, Daly, MB, Devilee, P, Diez, O, Ding, YC, Domchek, SM, Dörk, T, dos-Santos-Silva, I, Dunning, AM, Dwek, M, Eccles, DM, Eliassen, AH, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Flyger, H, Fostira, F, Friedman, E, Fritschi, L, Frost, D, Gago-Dominguez, M, Gapstur, SM, Garber, J, Garcia-Barberan, V, García-Closas, M, García-Sáenz, JA, Gaudet, MM & et al. 2021, 'Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers', Nature Communications, vol. 12, no. 1, p. 2986.
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A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4
Cole, AJ, Dickson, K-A, Liddle, C, Stirzaker, C, Shah, JS, Clifton-Bligh, R & Marsh, DJ 2021, 'Ubiquitin chromatin remodelling after DNA damage is associated with the expression of key cancer genes and pathways', Cellular and Molecular Life Sciences, vol. 78, no. 3, pp. 1011-1027.
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Correll, P, Feyer, A-M, Phan, P-T, Drake, B, Jammal, W, Irvine, K, Power, A, Muir, S, Ferdousi, S, Moubarak, S, Oytam, Y, Linden, J & Fisher, L 2021, 'Lumos: a statewide linkage programme in Australia integrating general practice data to guide system redesign', Integrated Healthcare Journal, vol. 3, no. 1, pp. e000074-e000074.
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ObjectiveWith ageing of the Australian population, more people are living longer and experiencing chronic or complex health conditions. The challenge is to have information that supports the integration of services across the continuum of settings and providers, to deliver person-centred, seamless, efficient and effective healthcare. However, in Australia, data are typically siloed within health settings, precluding a comprehensive view of patient journeys. Here, we describe the establishment of the Lumos programme—the first statewide linked data asset across primary care and other settings in Australia and evaluate its representativeness to the census population.Methods and analysisRecords extracted from general practices throughout New South Wales (NSW), Australia’s most populous state, were linked to patient records from acute and other settings. Innovative privacy and security technologies were employed to facilitate ongoing and regular updates. The marginal demographic distributions of the Lumos cohort were compared with the NSW census population by calculating multiple measures of representation to evaluate its generalisability.ResultsThe first Lumos programme data extraction linked 1.3 million patients’ general practice records to other NSW health system data. This represented 16% of the NSW population. The demographic distribution of patients in Lumos was >95% aligned to that of the NSW population in the calculated measures of representativeness.ConclusionThe Lumos programme delivers an enduring, regularly updated data resource, providing unique insights about statewide, cross-setting healthcare utilisation. General practice patients represented in the Lumos data asset are representative of the NSW population overall. Lumos ...
Coyne, JOC, Coutts, AJ, Newton, RU & Gregory Haff, G 2021, 'Relationships Between Different Internal and External Training Load Variables and Elite International Women’s Basketball Performance', International Journal of Sports Physiology and Performance, vol. 16, no. 6, pp. 871-880.
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Purpose: To investigate the relationships between internal and external training load (TL) metrics with elite international women’s basketball performance. Methods: Sessional ratings of perceived exertion, PlayerLoad™/minute, and training duration were collected from 13 elite international-level female basketball athletes (age 29.0 [3.7] y, stature 186.0 [9.8] cm, body mass 77.9 [11.6] kg) during the 18 weeks prior to the International Basketball Federation Olympic qualifying event for the 2016 Rio Olympic Games. Training stress balance, differential load, and the training efficiency index were calculated with 3 different smoothing methods. These TL metrics and their change in the last 21 days prior to competition were examined for their relationship to competition performance as coach ratings of performance. Results: For a number of TL variables, there were consistent significant small to moderate correlations with performance and significant small to large differences between successful and unsuccessful performances. However, these differences were only evident for external TL when using exponentially weighted moving averages to calculate TL. The variable that seemed most sensitive to performance was the change in training efficiency index in the last 21 days prior to competition (performance r = .47–.56, P < .001 and difference between successful and unsuccessful performance P < .001, f2 = 0.305–0.431). Conclusions: Internal and external TL variables were correlated with performance and distinguished between successful and unsuccessful performances among the same players during international w...
Coyne, JOC, Coutts, AJ, Newton, RU & Haff, GG 2021, 'The Influence of Mental Fatigue on Sessional Ratings of Perceived Exertion in Elite Open and Closed Skill Sports Athletes', Journal of Strength and Conditioning Research, vol. 35, no. 4, pp. 963-969.
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Abstract Coyne, JOC, Coutts, AJ, Newton, RU, and Haff, GG. The influence of mental fatigue on sessional ratings of perceived exertion in elite open and closed skill sports athletes. J Strength Cond Res 35(4): 963–969, 2021—The main purpose of this investigation was to examine influence of mental fatigue on sessional ratings of perceived exertion (sRPE) over a training week in elite athletes in open skill (OS, i.e., more unpredictable and externally paced sports) and closed skill (CS, i.e., more predictable and internally paced) sports. Visual analogue scales for mental fatigue, sRPE (CR-10 scale), and training duration were collected from an OS group (n = 27) of basketball and volleyball athletes and a CS group (n = 28) of weightlifting and track and field athletes during a typical training week 5 months before the 2016 Olympic Games. These variables were then examined using repeated measure correlations and linear mixed models with the level of significance set for the study at p < 0.05. There was a small significant correlation between mental fatigue and sRPE in the OS group (r = 0.23, p < 0.01), but not in the CS group (r = −0.07, p = 0.38). Mental fatigue had trivial influence on sRPE during individual sessions, but had a moderate effect on total sRPE over a week (p < 0.001, f 2 = 0.265) when accounting for type of sport, training duration, and injury/illness burden. It seems mental fatigue may not significantly influence sRPE in individual training sessions,...
Crabtree, J, Hudson, JL, Brockman, R & Newton‐John, T 2021, 'Spatial working memory, not IQ or executive function, discriminates early psychosis and clinically vulnerable creative individuals', Early Intervention in Psychiatry, vol. 15, no. 1, pp. 47-56.
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AbstractAimWhile associations between creativity and psychopathology have been well researched, the specific cognitive processes that distinguish highly creative from those with psychopathology warrant further investigation. This study will examine whether IQ, executive function, cognitive inhibition or spatial working memory differentiate individuals with early psychosis, clinically vulnerable creative individuals, creative controls and non‐creative controls.MethodsThe study sample consisted of 110 participants: early psychosis (n = 21); clinically vulnerable creative controls (n = 25); creative controls (n = 30) and non‐creative control (n = 34). The Diagnostic Interview for Psychosis assessed early psychosis participants and the Mini Neuropsychiatric Interview was used to screen for psychopathology in the remaining groups. Several cognitive tests were administered: IQ, neurocognitive measures of executive function and spatial working memory. Creativity was assessed using the Torrance Test of Creativity and Creative Achievement Questionnaire. A measure of vividness of mental imagery was also given.ResultsAcross all cognitive tests, spatial working memory differentiated the early psychosis group from both creative and non‐creative control groups. Spatial working memory predicted group membership but vivid imagery was a better predictor of creative achievement. The early psychosis, clinically vulnerable creative and creative groups all recorded significantly higher results on creative achievement and creative cognition compared to non‐creative controls.ConclusionsOur results provide further support for spatial working memory as an early neuro‐cognitive marker for early psychosis. Spatial working memor...
Cranfield, C, Whelan, D, Cox, C, Shearwin, K, Ho, J, Allen, T, Shibuya, R, Hibino, E, Hayashi, K, dos Remedios, C & Li, A 2021, 'Announcing the call for the Special Issue on “The Australian Society for Biophysics (ASB) – 2021 Meeting”', Biophysical Reviews, vol. 13, no. 4, pp. 485-486.
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This Commentary describes a call for submissions for the upcoming Special Issue focused on the research topics presented at the Australian Society of Biophysics (ASB) in 2020 and 2021. Submissions from past and present ASB members who could not attend these meetings are also welcome as contributions to this special issue.
Crook, A, Jacobs, C, Newton-John, T, Richardson, E & McEwen, A 2021, 'Patient and Relative Experiences and Decision-making About Genetic Testing and Counseling for Familial ALS and FTD', Alzheimer Disease & Associated Disorders, vol. 35, no. 4, pp. 374-385.
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Genetic testing and counseling is an emerging part of care for patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and their families. This scoping review aimed to map patients’ and relatives’ experiences of genetic testing and counseling for familial ALS and FTD and the factors influencing their decision to proceed with testing or counseling. Informed by the Joanna Briggs Institute methodology, 5 databases were systematically searched. Thirty studies from 39 references were included. A descriptive numerical summary analysis and narrative synthesis was conducted. Mostly positive diagnostic testing experiences were reported, but issues arose due to progressive disease and discordant results. Predictive testing impacted at-risk relatives, regardless of the result received, and psychosocial sequelae ranged from relief to guilt, worry or contemplating suicide. Four reproductive testing experiences were reported. Personal, familial and practical factors, and the lived experience of disease, informed decision-making. Greater uncertainty and complexity may be faced in familial ALS/FTD than in other late-onset neurodegenerative diseases due to clinical and genetic heterogeneity, and testing limitations. Genetic counseling models of care should consider this difference to ensure that individuals with, or at risk of, ALS/FTD are effectively managed. Implications for research and practice are discussed.
Crothers, A, Haeusler, GM, Slavin, MA, Babl, FE, Mechinaud, F, Phillips, R, Tapp, H, Padhye, B, Zeigler, D, Clark, J, Walwyn, T, Super, L, Alvaro, F, Thursky, K & De Abreu Lourenco, R 2021, 'Examining health-related quality of life in pediatric cancer patients with febrile neutropenia: Factors predicting poor recovery in children and their parents', EClinicalMedicine, vol. 40, pp. 101095-101095.
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Curtis, K, Sivabalan, P, Bedford, DS, Considine, J, D’Amato, A, Shepherd, N, Fry, M, Munroe, B & Shaban, RZ 2021, 'Implementation of a structured emergency nursing framework results in significant cost benefit', BMC Health Services Research, vol. 21, no. 1.
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Abstract Background Patients are at risk of deterioration on discharge from an emergency department (ED) to a ward, particularly in the first 72 h. The implementation of a structured emergency nursing framework (HIRAID) in regional New South Wales (NSW), Australia, resulted in a 50% reduction of clinical deterioration related to emergency nursing care. To date the cost implications of this are unknown. The aim of this study was to determine any net financial benefits arising from the implementation of the HIRAID emergency nursing framework. Methods This retrospective cohort study was conducted between March 2018 and February 2019 across two hospitals in regional NSW, Australia. Costs associated with the implementation of HIRAID at the study sites were calculated using an estimate of initial HIRAID implementation costs (AUD) ($492,917) and ongoing HIRAID implementation costs ($134,077). Equivalent savings per annum (i.e. in less patient deterioration) were calculated using projected estimates of ED admission and patient deterioration episodes via OLS regression with confidence intervals for incremental additional deterioration costs per episode used as the basis for scenario analysis. Results The HIRAID-equivalent savings per annum exceed the costs of implementation under all scenarios (Conservative, Expected and Optimistic). The estimated preliminary savings to the study sites per annum was $1,914,252 with a payback period of 75 days. Conservative projections estimated a net benefit of $1,813,760 per annum by 2022–23. The state-wide projected equivalent savings benefits of HIRAID equalled $227,585,008 per annum, by 2022–23. ...
Curtis, K, Sivabalan, P, Bedford, DS, Considine, J, D'Amato, A, Shepherd, N, Elphick, T, Shaban, RZ & Fry, M 2021, 'Treatments costs associated with inpatient clinical deterioration', Resuscitation, vol. 166, pp. 49-54.
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AimsThis study aimed to quantify the health economic treatment costs of clinical deterioration of patients within 72 h of admission via the emergency department.MethodsThis study was conducted between March 2018 and February 2019 in two hospitals in regional New South Wales, Australia. All patients admitted via the emergency department were screened for clinical deterioration (defined as initiation of a medical emergency team call, cardiac arrest or unplanned admission to Intensive Care Unit) within 72 h through the site clinical deterioration databases. Patient characteristics, including pre-existing conditions, diagnosis and administrative data were collected.Results1600 patients clinically deteriorated within 72 h of hospital admission. Linked treatment cost data were available for 929 (58%) of these patients across 352 Australian Refined Diagnosis Related Groups. The average (standard deviation) treatment costs for patients who deteriorated within 72 h was $26,778 ($34,007) compared to $7727 ($12,547). The average hospital length of stay of the deterioration group was nearly 8 days longer than patients without deterioration. When controlling for length of stay and Australian Refined Diagnosis Related Group codes, the incremental cost per episode of deterioration was $14,134.ConclusionClinical deterioration within 72 h of admission is associated with increased treatment costs irrespective of diagnosis, hospital length of stay and age. Implementation of interventions known to prevent patient deterioration require evaluation.
Daniels, B, Luckett, T, Holliday, S, Liauw, W, Lovell, M, Phillips, J, Rowett, D, John, TN, Tervonen, H & Pearson, S 2021, 'Patterns of oxycodone controlled release use in older people with cancer following public subsidy of oxycodone/naloxone formulations: An Australian population‐based study', Asia-Pacific Journal of Clinical Oncology, vol. 17, no. 1, pp. 68-78.
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AbstractAimPublic subsidy of the oxycodone/naloxone controlled release (CR) combination in December 2011 expanded the overall market for oxycodone CR in the general public in Australia; we evaluate its impact in people with cancer.MethodsWe used Repatriation Pharmaceutical Benefits dispensing data linked with the NSW Cancer Registry for Department of Veterans’ Affairs (DVA) healthcare card holders 65 years and older residing in NSW between 2004 and 2013 to identify clients with cancer and their opioid dispensings. We used interrupted time series analysis to model changes in monthly rates of oxycodone CR tablets dispensed and initiations. We performed a retrospective cohort study to examine changes in client characteristics and opioid utilization over time by comparing clients initiating oxycodone CR before and after subsidy.ResultsThe rate of oxycodone CR tablets dispensed/month increased by 20% from December 2011, due to uptake of the oxycodone/naloxone CR combination; monthly initiations increased immediately by 17%. Initiations of buprenorphine, fentanyl, and morphine declined from December 2011. DVA healthcare card holders were significantly more likely to initiate the 5 mg oxycodone CR formulation; more likely to use immediate release oxycodone in the 90 days following initiation; and less likely to use a weak opioid in the 90 days preceding oxycodone CR initiation following December 2011 than they were prior to that time.ConclusionsThe public subsidy of the oxycodone/naloxone CR formulation expanded the overall oxycodone CR market for DVA healthcare card holders with cancer. Our findings highlight the need for updated guidelines around risk management for opioid treatment in patients with cancer...
De Abreu Lourenço, R, Devlin, N, Howard, K, Ong, JJ, Ratcliffe, J, Watson, J, Willing, E & Huynh, E 2021, 'Giving a Voice to Marginalised Groups for Health Care Decision Making', The Patient - Patient-Centered Outcomes Research, vol. 14, no. 1, pp. 5-10.
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De Abreu Lourenco, R, McCarthy, MC, McMillan, LJ, Sullivan, M & Gillam, L 2021, 'Understanding decisions to participate in genomic medicine in children's cancer care: A comparison of what influences parents, health care providers, and the general community', Pediatric Blood & Cancer, vol. 68, no. 8.
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AbstractBackgroundThe emerging role of genomically guided precision medicine in pediatric cancer care presents significant clinical, practical, and ethical challenges. We investigated the factors that influence decision‐making in genomic medicine from the perspective of different stakeholders in the context of difficult‐to‐treat childhood cancer.MethodsHealth care providers (HCPs), parents of childhood cancer survivors, and general community members completed an online discrete choice experiment survey. Respondents considered whether to recommend (HCPs) or choose (parents/community) a genomically guided approach to pediatric cancer treatment. Respondents completed eight choice questions varying by survival benefit, prognosis, likelihood of finding a target, quality of life (QoL), HCP/parent preference, need for biopsy, cost, and who pays. Data were analyzed using a probability regression model, with findings expressed as relative importance, stated importance, and marginal willingness to pay (mWTP).ResultsOne hundred twenty‐six HCPs, 130 parents, and 531 community members participated. The probability of recommending/choosing genomically guided treatment increased significantly with better prognosis, survival benefit, improvements in QoL, and decision‐making partner support. It decreased with increasing costs and if parents paid for treatment. HCPs were more responsive to all factors but were most influenced by survival outcomes, and parents and community members by QoL. In contrast to these forced choice preference results, HCPs stated they were most influenced by QoL and community members by survival.ConclusionOur findings support the primacy of QoL in genomic decision‐making, with some differences ...
de Feria Cardet, RE, Hofman, MS, Segard, T, Yim, J, Williams, S, Francis, RJ, Frydenberg, M, Lawrentschuk, N, Murphy, DG & De Abreu Lourenco, R 2021, 'Is Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Imaging Cost-effective in Prostate Cancer: An Analysis Informed by the proPSMA Trial', European Urology, vol. 79, no. 3, pp. 413-418.
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Background
Before integrating prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) into routine care, it is important to assess if the benefits justify the differences in resource use.
Objective
To determine the cost-effectiveness of PSMA-PET/CT when compared with conventional imaging.
Design, setting, and participants
A cost-effectiveness analysis was developed using data from the proPSMA study. proPSMA included patients with high-risk prostate cancer assigned to conventional imaging or
68Ga-PSMA-11 PET/CT with planned health economics data collected. The cost-effectiveness analysis was conducted from an Australian societal perspective.
Intervention
68Ga-PSMA-11 PET/CT compared with conventional imaging (CT and bone scan).
Outcome measurements and statistical analysis
The primary outcome from proPSMA was diagnostic accuracy (nodal and distant metastases). This informed a decision tree analysis of the cost per accurate diagnosis.
Results and limitations
The estimated cost per scan for PSMA PET/CT was AUD$1203, which was less than the conventional imaging cost at AUD$1412. PSMA PET/CT was thus dominant, having both better accuracy and a lower cost. This resulted in a cost of AUD$959 saved per additional accurate detection of nodal disease, and AUD$1412 saved for additional accurate detection of distant metastases. The results were most sensitive to variations in the number of men scanned for each
68Ga-PSMA-11 production run. Subsequent research is required to assess the long-term costs and benefits of PSMA PET/CT-directed care.
Conclusions
PSMA PET/CT has lower direct comparative costs and greater accuracy compared to conventional imaging for initial staging of men with high-risk prostate cancer. This provides a compelling case for adopting PSMA PET/CT into clinical practice.
Patient summary
The proPSMA study demonstrat...
Deng, K, Zhang, X, Liu, Y, Zhang, L, Wang, G, Feng, M, Oliver, BG, Wang, L, Hansbro, PM, Qin, L, Xie, M, Chen, ZH, Simpson, J, Zhang, J, Li, WM, Wang, G & Gibson, PG 2021, 'Heterogeneity of Paucigranulocytic Asthma: A Prospective Cohort Study with Hierarchical Cluster Analysis', The Journal of Allergy and Clinical Immunology: In Practice, vol. 9, no. 6, pp. 2344-2355.
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BACKGROUND: Asthma, a heterogeneous disease, can be divided into 4 inflammatory phenotypes using induced sputum cell counts-eosinophilic asthma (EA), neutrophilic asthma (NA), mixed granulocytic asthma, and paucigranulocytic asthma (PGA). Although research has focused on EA and NA, there is little known about PGA. OBJECTIVE: To study the heterogeneity of PGA and identify possible PGA clusters to guide clinical treatment. METHODS: Patients with PGA were grouped by hierarchical cluster analysis and enrolled into a prospective cohort study to validate the clusters, relative to future risk of asthma exacerbations in a real-world setting. Clusters were validated by tree analysis in a separate population. Finally, we explored PGA stability. RESULTS: Cluster analysis of 145 patients with PGA identified 3 clusters: cluster 1 (n = 110, 75.9%) was 'mild PGA,' cluster 2 (n = 20, 13.8%) was 'PGA with psychological dysfunction and rhinoconjunctivitis and other allergic diseases,' and cluster 3 (n = 15, 10.3%) was 'smoking-associated PGA.' Cluster 3 had significantly increased risk of severe exacerbation (relative risk [RR] = 6.43, P = .01), emergency visit (RR = 8.61, P = .03), and hospitalization (RR = 12.94, P < .01). Results of the cluster analysis were successfully validated in an independent PGA population classified using decision tree analysis. Although PGA can transform into or develop from other phenotypes, 70% were stable over time. CONCLUSIONS: Among 3 identified PGA clusters, cluster 3 had a higher risk of severe exacerbation. PGA heterogeneity indicates the requirement of novel targeted interventions.
Deplazes, E, Tafalla, BD, Murphy, C, White, J, Cranfield, CG & Garcia, A 2021, 'Calcium Ion Binding at the Lipid–Water Interface Alters the Ion Permeability of Phospholipid Bilayers', Langmuir, vol. 37, no. 48, pp. 14026-14033.
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Dickson, TJ & Darcy, S 2021, 'A question of time: a brief systematic review and temporal extension of the socioecological framework as applied in sport and physical activity', Translational Sports Medicine, vol. 4, no. 2, pp. 163-173.
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Ding, L, Moloudi, R & Warkiani, ME 2021, 'Bioreactor-Based Adherent Cells Harvesting from Microcarriers with 3D Printed Inertial Microfluidics', pp. 257-266.
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Ding, L, Radfar, P, Rezaei, M & Warkiani, ME 2021, 'An easy-to-operate method for single-cell isolation and retrieval using a microfluidic static droplet array', Microchimica Acta, vol. 188, no. 8, pp. 1-11.
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In-depth study of cellular heterogeneity of rare cells (e.g. circulating tumour cells (CTCs) and circulating foetal cells (CFCs)) is greatly needed in disease management but has never been completely explored due to the current technological limitations. We have developed a retrieval method for single-cell detection using a static droplet array (SDA) device through liquid segmentation with almost no sample loss. We explored the potential of using SDA for low sample input and retrieving the cells of interest using everyday laboratory equipment for downstream molecular analysis. This single-cell isolation and retrieval method is low-cost, rapid and provides a solution to the remaining challenge for single rare cell detection. The entire process takes less than 15 min, is easy to fabricate and allows for on-chip analysis of cells in nanolitre droplets and retrieval of desired droplets. To validate the applicability of our device and method, we mimicked detection of single CTCs by isolating and retrieving single cells and perform real-time PCR on their mRNA contents.
Disalvo, D, Agar, M, Caplan, G, Murtagh, FEM, Luckett, T, Heneka, N, Hickman, L, Kinchin, I, Trethewie, S, Sheehan, C, Urban, K, Cohen, J, Harlum, J, Long, B, Parker, T, Schaefer, I & Phillips, J 2021, 'Virtual models of care for people with palliative care needs living in their own home: A systematic meta-review and narrative synthesis', Palliative Medicine, vol. 35, no. 8, pp. 1385-1406.
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Background: Access to palliative care in the community enables people to live in their preferred place of care, which is often home. Community palliative care services struggle to provide timely 24-h services to patients and family. This has resulted in calls for ‘accessible and flexible’ models of care that are ‘responsive’ to peoples’ changing palliative care needs. Digital health technologies provide opportunities to meet these requirements 24-h a day. Aim: To identify digital health technologies that have been evaluated for supporting timely assessment and management of people living at home with palliative care needs and/or their carer(s), and the evidence-base for each. Design: A systematic review of systematic reviews (‘meta-review’). Systematic reviews evaluating evidence for virtual models of palliative or end-of-life care using one or more digital health technologies were included. Systematic reviews were evaluated using the Risk of Bias Tool for Systematic Reviews. A narrative approach was used to synthesise results. Data sources: Medline, Embase, Web of Science, CINAHL and Cochrane Database of systematic reviews were searched for English-language reviews published between 2015 and 2020. Results: The search yielded 2266 articles, of which 12 systematic reviews met criteria. Sixteen reviews were included in total, after four reviews were found via handsearching. Other than scheduled telehealth, video-conferencing, or after-hours telephone support, little evidence was found for digital health technologies used to deliver virtual models of palliative care. Conclusions: There are opportunities t...
Doerflinger, M, Haeusler, GM, Li-Wai-Suen, CSN, Clark, JE, Slavin, M, Babl, FE, Allaway, Z, Mechinaud, F, Smyth, GK, De Abreu Lourenco, R, Phillips, B, Pellegrini, M & Thursky, KA 2021, 'Procalcitonin and Interleukin-10 May Assist in Early Prediction of Bacteraemia in Children With Cancer and Febrile Neutropenia', Frontiers in Immunology, vol. 12.
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ObjectivesFebrile neutropenia (FN) causes treatment disruption and unplanned hospitalization in children with cancer. Serum biomarkers are infrequently used to stratify these patients into high or low risk for serious infection. This study investigated plasma abundance of cytokines in children with FN and their ability to predict bacteraemia.MethodsThirty-three plasma cytokines, C-reactive protein (CRP) and procalcitonin (PCT) were measured using ELISA assays in samples taken at FN presentation (n = 79) and within 8–24 h (Day 2; n = 31). Optimal thresholds for prediction of bacteraemia were identified and the predictive ability of biomarkers in addition to routinely available clinical variables was assessed.ResultsThe median age of included FN episodes was 6.0 years and eight (10%) had a bacteraemia. On presentation, elevated PCT, IL-10 and Mip1-beta were significantly associated with bacteraemia, while CRP, IL-6 and IL-8 were not. The combination of PCT (≥0.425 ng/ml) and IL-10 (≥4.37 pg/ml) had a sensitivity of 100% (95% CI 68.8–100%) and specificity of 89% (95% CI 80.0–95.0%) for prediction of bacteraemia, correctly identifying all eight bacteraemia episodes and classifying 16 FN episodes as high-risk. There was limited additive benefit of incorporating clinical variables to this model. On Day 2, there was an 11-fold increase in PCT in episodes with a bacteraemia which was significantly higher than that observed in the non-bacteraemia episodes.ConclusionElevated PCT and IL-10 accurately identified all bacteraemia episodes in our FN cohort and may enhance the early risk stratification process in this population. Prospective validation and implementation is required to determine the impact on health service utilisation.
Donkor, A, Luckett, T, Aranda, S, Vanderpuye, V & Phillips, JL 2021, 'Development of the ‘REadiness SElf-assessment (RESEA) guide’ to assist low and middle-income countries with establishing safe and sustainable radiotherapy services: a pragmatic sequential mixed qualitative methods project', BMC Health Services Research, vol. 21, no. 1.
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Abstract Background Improving access to radiotherapy services in low and middle-income countries (LMICs) is challenging. Many LMICs’ radiotherapy initiatives fail because of multi-faceted barriers leading to significant wastage of scarce resources. Supporting LMICs to self-assess their readiness for establishing radiotherapy services will help to improve cancer outcomes by ensuring safe, effective and sustainable evidenced-based cancer care. The aim of the study was to develop practical guidance for LMICs on self-assessing their readiness to establish safe and sustainable radiotherapy services. Methods The Access to Radiotherapy for Cancer treatment (ARC) Project was a pragmatic sequential mixed qualitative methods design underpinned by the World Health Organisation’s ‘Innovative Care for Chronic Conditions Framework’ and ‘Health System Building Blocks Framework for Action’ conceptual frameworks. This paper reports on the process of overall data integration and meta-inference from previously published components comprising a systematic review and two-part qualitative study (semi-structured interviews and a participant validation process). The meta-inferences enabled a series of radiotherapy readiness self-assessment requirements to be generated, formalised as a REadiness SElf-Assessment (RESEA) Guide’ for use by LMICs. Findings The meta-inferences identified a large number of factors that acted as facilitators and/or barriers, depending on the situation, which include: awareness and advocacy; political leadership; epidemiological data; financial resources; basic physical ...
Eager, D, Chapman, C, Qi, Y, Ishac, K & Hossain, MI 2021, 'Additional Criteria for Playground Impact Attenuating Sand', Applied Sciences, vol. 11, no. 19, pp. 8805-8805.
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Falls within children’s playgrounds result in long bone and serious injuries. To lower the likelihood and severity of injury, impact attenuating surfaces (IAS) are installed within the impact area (fall zone). There are three primary IAS materials used, namely: granulated rubber products, wood fibre products, and sand. There is a deficiency with existing IAS test methods in that they do not take account of sand degradation over time. When children use the playground, sand degradation can occur when sand produces fines and smaller particles with low sphericity and angular which fill the voids between the sand particles. These fines and smaller particles tend to bind the sand and lower its impact attenuating performance. This paper proposes an additional IAS test to eliminate sands that degrade above an established threshold rate after installation due to normal usage. IAS degradation properties of fifteen IAS sands were tested including sand particle shape, sand particle distribution, percentage fines and sand particle degradation. This accelerated ageing test method is applicable only to sands and not rubber or wood fibre IAS products. The best IAS sands were sourced from quarries located on rivers that had eroded volcanic outcrops. These sands were shown to degrade the least and had little to no fines, and their particle shape was rounded to well-rounded. The most reliable source for good quality IAS sands on these rivers was on specific bends. The sand mined at these locations consistently had a tight particle size distribution.
Eager, D, Halkon, B, Zhou, S, Walker, P, Covey, K & Braiden, S 2021, 'Greyhound Racing Track Lure Systems—Acoustical Measurements within and Adjacent to the Starting Boxes', Technologies, vol. 9, no. 4, pp. 74-74.
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This study investigates and compares the acoustic signatures of a traditional wire-cable-pulled lure system and two alternative battery-operated lure systems jointly developed by Covey Associates Pty. Ltd. and Steriline Pty. Ltd. to eliminate the hazardous steel-wire cable and make the sport of greyhound racing safer for greyhounds, participants and spectators. The acoustical measurements of these three lure systems were conducted at the Murray Bridge greyhound racing track. The lure sounds were measured by the high-frequency Brüel & Kjær (B&K) Type 4191 microphones for the 395 m and 455 m starts at two positions: within the starting box and on the track adjacent to the starting boxes. The measurements capture the sounds that the greyhounds hear before and after the opening of the starting box gate. The frequency-domain analysis and sound quality analysis were conducted to compare the lure sounds. It was found when the battery-lure was installed with all nylon rollers, it presented less sound energy and lower frequency than the traditional wire-cable-pulled lure. When two of the nylon rollers were replaced with steel rollers, the battery-operated lure emitted a louder and higher frequency sound than the traditional wire-cable-pulled lure. The different acoustic characteristics of these lure systems suggest future research is warranted on the reaction of greyhounds to different lure sounds, particularly their excitement level within the starting box as the lure approaches. This initial research also suggests some greyhounds may not clearly hear the battery-operated lure with all nylon rollers approaching the starting boxes and the timing of these greyhounds to jump may be delayed, particularly during high wind conditions.
Eager, D, Hossain, I, Ishac, K & Robins, S 2021, 'Analysis of Racing Greyhound Path Following Dynamics Using a Tracking System', Animals, vol. 11, no. 9, pp. 2687-2687.
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The University of Technology Sydney (UTS) has been working closely with the Australasian greyhound industry for more than 5 years to reduce greyhound race-related injuries. During this period, UTS has developed and deployed several different techniques including inertial measurement units, drones, high-frame-rate cameras, track geometric surveys, paw print analysis, track soil spring-force analysis, track maintenance data, race injury data, race computer simulation and modelling to assist in this task. During the period where the UTS recommendations have been adopted, the injury rate has dropped significantly. This has been achieved by animal welfare interventions that lower racing congestion, and lower transient forces and jerk rates the greyhounds experience during a race. This study investigated the use of a greyhound location tracing system where small and lightweight signal emitting devices were placed inside a pocket in the jackets of racing greyhounds. The system deployed an enhanced version of a player tracking system currently used to track the motion of human athletes. Greyhounds gallop at speeds of almost 20 m/s and are known to change their heading direction to exceed a yaw rate of 0.4 rad/s. The high magnitudes of velocity, acceleration and jerk posed significant technical challenges, as the greyhounds pushed the human tracking system beyond its original design limits. Clean race data gathered over a six-month period were analysed and presented for a typical 2-turn greyhound racing track. The data confirmed that on average, greyhounds ran along a path that resulted in the least energy wastage, which includes smooth non-linear paths that resemble easement curves at the transition between the straights to the semi-circular bends. This study also verified that the maximum jerk levels greyhounds experienced while racing were lower than the jerk levels that had been predicted with simulations and modelling for the track path. Furthermore...
Elazezy, M, Schwentesius, S, Stegat, L, Wikman, H, Werner, S, Mansour, WY, Failla, AV, Peine, S, Müller, V, Thiery, JP, Ebrahimi Warkiani, M, Pantel, K & Joosse, SA 2021, 'Emerging Insights into Keratin 16 Expression during Metastatic Progression of Breast Cancer', Cancers, vol. 13, no. 15, pp. 3869-3869.
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Keratins are the main identification markers of circulating tumor cells (CTCs); however, whether their deregulation is associated with the metastatic process is largely unknown. Previously we have shown by in silico analysis that keratin 16 (KRT16) mRNA upregulation might be associated with more aggressive cancer. Therefore, in this study, we investigated the biological role and the clinical relevance of K16 in metastatic breast cancer. By performing RT-qPCR, western blot, and immunocytochemistry, we investigated the expression patterns of K16 in metastatic breast cancer cell lines and evaluated the clinical relevance of K16 expression in CTCs of 20 metastatic breast cancer patients. High K16 protein expression was associated with an intermediate mesenchymal phenotype. Functional studies showed that K16 has a regulatory effect on EMT and overexpression of K16 significantly enhanced cell motility (p < 0.001). In metastatic breast cancer patients, 64.7% of the detected CTCs expressed K16, which was associated with shorter relapse-free survival (p = 0.0042). Our findings imply that K16 is a metastasis-associated protein that promotes EMT and acts as a positive regulator of cellular motility. Furthermore, determining K16 status in CTCs provides prognostic information that helps to identify patients whose tumors are more prone to metastasize.
Es, HA, Cox, TR, Sarafraz-Yazdi, E, Thiery, JP & Warkiani, ME 2021, 'Pirfenidone Reduces Epithelial–Mesenchymal Transition and Spheroid Formation in Breast Carcinoma through Targeting Cancer-Associated Fibroblasts (CAFs)', Cancers, vol. 13, no. 20, pp. 5118-5118.
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The aim of this study was to assess the effects of pirfenidone (PFD) on promoting epithelial–mesenchymal-transition (EMT) and stemness features in breast carcinoma cells through targeting cancer-associated-fibroblasts (CAFs). Using The Cancer Genome Atlas (TCGA) database, we analyzed the association between stromal index, EMT, and stemness-related genes across 1084 breast cancer patients, identifying positive correlation between YAP1, EMT, and stemness genes in samples with a high-stromal index. We monitored carcinoma cell invasion and spheroid formation co-cultured with CAFs in a 3D microfluidic device, followed by exposing carcinoma cells, spheroids, and CAFs with PFD. We depicted a positive association between the high-stromal index and the expression of EMT and stemness genes. High YAP1 expression in samples correlated with more advanced EMT status and stromal index. Additionally, we found that CAFs promoted spheroid formation and induced the expression of YAP1, VIM, and CD44 in spheroids. Treatment with PFD reduced carcinoma cell migration and decreased the expression of these genes at the protein level. The cytokine profiling showed significant depletion of various EMT- and stemness-regulated cytokines, particularly IL8, CCL17, and TNF-beta. These data highlight the potential application of PFD on inhibiting EMT and stemness in carcinoma cells through the targeting of critical cytokines.
Eyni, H, Ghorbani, S, Nazari, H, Hajialyani, M, Razavi Bazaz, S, Mohaqiq, M, Ebrahimi Warkiani, M & Sutherland, DS 2021, 'Advanced bioengineering of male germ stem cells to preserve fertility', Journal of Tissue Engineering, vol. 12, pp. 204173142110605-204173142110605.
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In modern life, several factors such as genetics, exposure to toxins, and aging have resulted in significant levels of male infertility, estimated to be approximately 18% worldwide. In response, substantial progress has been made to improve in vitro fertilization treatments (e.g. microsurgical testicular sperm extraction (m-TESE), intra-cytoplasmic sperm injection (ICSI), and round spermatid injection (ROSI)). Mimicking the structure of testicular natural extracellular matrices (ECM) outside of the body is one clear route toward complete in vitro spermatogenesis and male fertility preservation. Here, a new wave of technological innovations is underway applying regenerative medicine strategies to cell-tissue culture on natural or synthetic scaffolds supplemented with bioactive factors. The emergence of advanced bioengineered systems suggests new hope for male fertility preservation through development of functional male germ cells. To date, few studies aimed at in vitro spermatogenesis have resulted in relevant numbers of mature gametes. However, a substantial body of knowledge on conditions that are required to maintain and mature male germ cells in vitro is now in place. This review focuses on advanced bioengineering methods such as microfluidic systems, bio-fabricated scaffolds, and 3D organ culture applied to the germline for fertility preservation through in vitro spermatogenesis.
Fang, G, Lu, H, Aboulkheyr Es, H, Wang, D, Liu, Y, Warkiani, ME, Lin, G & Jin, D 2021, 'Unidirectional intercellular communication on a microfluidic chip', Biosensors and Bioelectronics, vol. 175, pp. 112833-112833.
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Cell co-culture serves as a standard method to study intercellular communication. However, random diffusion of signal molecules during co-culture may arouse crosstalk among different types of cells and hide directive signal-target responses. Here, a microfluidic chip is proposed to study unidirectional intercellular communication by spatially controlling the flow of the signal molecules. The chip contains two separated chambers connected by two channels where the culture media flows oppositely. A zigzag signal-blocking channel is designed to study the function of a specific signal. The chip is applied to study the unidirectional communication between tumor cells and stromal cells. It shows that the expression of α-smooth muscle actin (a marker of cancer-associated fibroblast (CAF)) of both MRC-5 fibroblasts and mesenchymal stem cells can be up-regulated only by the secreta from invasive MDA-MB-231 cells, but not from non-invasive MCF-7 cells. The proliferation of the tumor cells can be improved by the stromal cells. Moreover, transforming growth factor beta 1 is found as one of the main factors for CAF transformation via the signal-blocking function. The chip achieves unidirectional cell communication along X-axis, signal concentration gradient along Y-axis and 3D cell culture along Z-axis, which provides a useful tool for cell communication studies.
Fang, L, Ruan, M, Yang, S, Qu, X, Chen, H, Zhao, J & Cheng, J 2021, 'Prednisone combined with letrozole reduced risk of ovarian hyperstimulation syndrome (OHSS) in women undergoing long-term gonadotropin-releasing hormone analog treatment', Annals of Palliative Medicine, vol. 10, no. 8, pp. 8837-8847.
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Farahmandian, S & Hoang, DB 2021, 'Policy-based Interaction Model for Detection and Prediction of Cloud Security Breaches', Journal of Telecommunications and the Digital Economy, vol. 9, no. 2, pp. 92-116.
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The ever-increasing number and gravity of cyberattacks against the cloud's assets, together with the introduction of new technologies, have brought about many severe cloud security issues. The main challenge is finding effective mechanisms for constructing dynamic isolation boundaries for securing cloud assets at different cloud infrastructure levels. Our security architecture tackles these issues by introducing a policy-driven interaction model. The model is governed by cloud system security policies and constrained by cloud interacting entities' locations and levels. Security policies are used to construct security boundaries between cloud objects at their interaction level. The novel interaction model relies on its unique parameters to develop an agile detection and prediction mechanism of security threats against cloud resources. The proposed policy-based interaction model and its interaction security algorithms are developed to protect cloud resources. The model deals with external and internal interactions among entities representing diverse participating elements of different complexity levels in a cloud environment. We build a security controller and simulate various scenarios for testing the proposed interaction model and security algorithms.
Fardell, JE, Wakefield, CE, De Abreu Lourenco, R, Signorelli, C, McCarthy, M, McLoone, J, Osborn, M, Gabriel, M, Anazodo, A, Alvaro, F, Lockwood, L, Walwyn, T, Skeen, J, Tillemans, R & Cohn, RJ 2021, 'Long‐term health‐related quality of life in young childhood cancer survivors and their parents', Pediatric Blood & Cancer, vol. 68, no. 12.
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AbstractPurposeFew studies have investigated the health‐related quality of life (HRQoL) of young childhood cancer survivors and their parents. This study describes parent and child cancer survivor HRQoL compared to population norms and identifies factors influencing child and parent HRQoL.MethodsWe recruited parents of survivors who were currently <16 years, and >5 years postdiagnosis. Parents reported on their child's HRQoL (Kidscreen‐10), and their own HRQoL (EQ‐5D‐5L). Parents rated their resilience and fear of cancer recurrence and listed their child's cancer‐related late effects.ResultsOne hundred eighty‐two parents of survivors (mean age = 12.4 years old and 9.7 years postdiagnosis) participated. Parent‐reported child HRQoL was significantly lower than population norms (48.4 vs. 50.7, p < .009). Parents most commonly reported that their child experienced sadness and loneliness (18.1%). Experiencing more late effects and receiving treatments other than surgery were associated with worse child HRQoL. Parents’ average HRQoL was high (0.90) and no different to population norms. However 38.5% of parents reported HRQoL that was clinically meaningfully different from perfect health, and parents experienced more problems with anxiety/depression (43.4%) than population norms (24.7%, p < .0001). Worse child HRQoL, lower parent resilience, and higher fear of recurrence was associated with worse parent HRQoL.ConclusionsParents report that young survivors experience small but significant ongoing reductions in HRQoL. While overall mean levels of HRQoL were no different to population norms, a subset of parents reported HRQoL that was clinically ...
Fardjahromi, MA, Ejeian, F, Razmjou, A, Vesey, G, Mukhopadhyay, SC, Derakhshan, A & Warkiani, ME 2021, 'Enhancing osteoregenerative potential of biphasic calcium phosphates by using bioinspired ZIF8 coating', Materials Science and Engineering: C, vol. 123, pp. 111972-111972.
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Biphasic calcium phosphate ceramics (BCPs) have been extensively used as a bone graft in dental clinics to reconstruct lost bone in the jaw and peri-implant hard tissue due to their good bone conduction and similar chemical structure to the teeth and bone. However, BCPs are not inherently osteoinductive and need additional modification and treatment to enhance their osteoinductivity. The present study aims to develop an innovative strategy to improve the osteoinductivity of BCPs using unique features of zeolitic imidazolate framework-8 (ZIF8). In this method, commercial BCPs (Osteon II) were pre-coated with a zeolitic imidazolate framework-8/polydopamine/polyethyleneimine (ZIF8/PDA/PEI) layer to form a uniform and compact thin film of ZIF8 on the surface of BCPs. The surface morphology and chemical structure of ZIF8 modified Osteon II (ZIF8-Osteon) were confirmed using various analytical techniques such as XRD, FTIR, SEM, and EDX. We evaluated the effect of ZIF8 coating on cell attachment, growth, and osteogenic differentiation of human adipose-derived mesenchymal stem cells (hADSCs). The results revealed that altering the surface chemistry and topography of Osteon II using ZIF8 can effectively promote cell attachment, proliferation, and bone regeneration in both in vitro and in vivo conditions. In conclusion, the method applied in this study is simple, low-cost, and time-efficient and can be used as a versatile approach for improving osteoinductivity and osteoconductivity of other types of alloplastic bone grafts.
Fisher, BM, Tang, KD, Warkiani, ME, Punyadeera, C & Batstone, MD 2021, 'A pilot study for presence of circulating tumour cells in adenoid cystic carcinoma', International Journal of Oral and Maxillofacial Surgery, vol. 50, no. 8, pp. 994-998.
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Adenoid cystic carcinoma (ACC) is a rare salivary gland neoplasm with a poor long-term prognosis due to multiple recurrences and distant metastatic spread. Circulating tumour cells (CTCs) are tumour cells shed from a primary, recurrent, or metastatic cancer that are detectable in the blood or lymphatics. There is no literature to date confirming the presence of CTCs in ACC. The aim of this study was to determine whether CTCs are detectable in ACC. Blood samples were collected from eight patients with histologically confirmed ACC. The TNM stage of the tumour was recorded, as well as any prior treatment. CTCs were isolated by spiral microfluidics and detected by immunofluorescence staining. Three of the eight patients recruited (32.5%) had staining consistent with the presence of CTCs. Of these three patients with detectable CTCs, one had confirmed pulmonary metastasis, one had suspected pulmonary metastasis and was awaiting confirmation, and one had local recurrence confirmed on re-resection. One patient with known isolated pulmonary metastasis had previously undergone a lung metastasectomy and did not have CTCs detected. CTCs are detectable in ACC. In this small patient sample, CTCs were found to be present in those patients with recurrent local disease and known distant metastatic disease. CTCs in ACC should be investigated further for their potential use as an adjunct in staging, prognosis, and the detection of recurrence.
Gadipudi, N, Elamvazuthi, I, Lu, C-K, Paramasivam, S & Su, S 2021, 'WPO-Net: Windowed Pose Optimization Network for Monocular Visual Odometry Estimation', Sensors, vol. 21, no. 23, pp. 8155-8155.
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Visual odometry is the process of estimating incremental localization of the camera in 3-dimensional space for autonomous driving. There have been new learning-based methods which do not require camera calibration and are robust to external noise. In this work, a new method that do not require camera calibration called the “windowed pose optimization network” is proposed to estimate the 6 degrees of freedom pose of a monocular camera. The architecture of the proposed network is based on supervised learning-based methods with feature encoder and pose regressor that takes multiple consecutive two grayscale image stacks at each step for training and enforces the composite pose constraints. The KITTI dataset is used to evaluate the performance of the proposed method. The proposed method yielded rotational error of 3.12 deg/100 m, and the training time is 41.32 ms, while inference time is 7.87 ms. Experiments demonstrate the competitive performance of the proposed method to other state-of-the-art related works which shows the novelty of the proposed technique.
Garcia, MV, Agar, MR, Soo, W-K, To, T & Phillips, JL 2021, 'Screening Tools for Identifying Older Adults With Cancer Who May Benefit From a Geriatric Assessment', JAMA Oncology, vol. 7, no. 4, pp. 616-616.
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Importance
Older adults with cancer are at risk of overtreatment or undertreatment when decision-making is based solely on chronological age. Although a geriatric assessment is recommended to inform care, the time and expertise required limit its feasibility for all patients. Screening tools offer the potential to identify those who will benefit most from a geriatric assessment. Consensus about the optimal tool to use is lacking.
Objective
To appraise the evidence on screening tools used for older adults with cancer and identify an optimal screening tool for older adults with cancer who may benefit from geriatric assessment.
Evidence Review
Systematic review of 4 databases (MEDLINE, Embase, CINAHL [Cumulative Index to Nursing and Allied Health Literature], and PubMed) with narrative synthesis from January 1, 2000, to March 14, 2019. Studies reporting on the diagnostic accuracy and use of validated screening tools to identify older adults with cancer who need a geriatric assessment were eligible for inclusion. Data were analyzed from March 14, 2019, to March 23, 2020.
Findings
Seventeen unique studies were included, reporting on the use of 12 screening tools. Most studies were prospective cohort studies (n = 11) with only 1 randomized clinical trial. Not all studies reported time taken to administer the screening tools. The Geriatric-8 (G8) (n = 12) and the Vulnerable Elders Survey-13 (VES-13) (n = 9) were the most frequently evaluated screening tools. The G8 scored better in sensitivity and the VES-13 in specificity. Other screening tools evaluated include the Groningen Frailty Index, abbreviated comprehensive geriatric assessment, and Physical Performance Test in 2 studies each. All other screening tools were evaluated in 1 study each.
Conclusions and Relevance
To date, the G8 and VES-13 have the most evidence to recommend their use to inform the need for geriatric assessment. When choosing a screening tool, clinicians will need to weigh the tradeoffs between se...
Ghasemian, R, Shamshirian, A, Heydari, K, Malekan, M, Alizadeh‐Navaei, R, Ebrahimzadeh, MA, Ebrahimi Warkiani, M, Jafarpour, H, Razavi Bazaz, S, Rezaei Shahmirzadi, A, Khodabandeh, M, Seyfari, B, Motamedzadeh, A, Dadgostar, E, Aalinezhad, M, Sedaghat, M, Razzaghi, N, Zarandi, B, Asadi, A, Yaghoubi Naei, V, Beheshti, R, Hessami, A, Azizi, S, Mohseni, AR & Shamshirian, D 2021, 'The role of vitamin D in the age of COVID‐19: A systematic review and meta‐analysis', International Journal of Clinical Practice, vol. 75, no. 11, pp. 1-16.
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BackgroundEvidence recommends that vitamin D might be a crucial supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a systematic review and meta-analysis in order to maximise the use of everything that exists about the role of vitamin D in the COVID-19.MethodsA systematic search was performed in PubMed, Scopus, Embase and Web of Science up to December 18, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review.ResultsTwenty-three studies containing 11 901 participants entered into the meta-analysis. The meta-analysis indicated that 41% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 29%-55%), and in 42% of patients, levels of vitamin D were insufficient (95% CI, 24%-63%). The serum 25-hydroxyvitamin D concentration was 20.3 ng/mL among all COVID-19 patients (95% CI, 12.1-19.8). The odds of getting infected with SARS-CoV-2 are 3.3 times higher among individuals with vitamin D deficiency (95% CI, 2.5-4.3). The chance of developing severe COVID-19 is about five times higher in patients with vitamin D deficiency (OR: 5.1, 95% CI, 2.6-10.3). There is no significant association between vitamin D status and higher mortality rates (OR: 1.6, 95% CI, 0.5-4.4).ConclusionThis study found that most of the COVID-19 patients were suffering from vitamin D deficiency/insufficiency. Also, there is about three times higher chance of getting infected with SARS-CoV-2 among vitamin-D-deficient individuals and about five times higher probability of developing the severe disease in vitamin-D-deficient patients. Vitamin D deficiency showed no significant association with mortality rates in this population.
Gheisari, S, Shariflou, S, Phu, J, Kennedy, PJ, Agar, A, Kalloniatis, M & Golzan, SM 2021, 'A combined convolutional and recurrent neural network for enhanced glaucoma detection', Scientific Reports, vol. 11, no. 1, p. 1945.
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AbstractGlaucoma, a leading cause of blindness, is a multifaceted disease with several patho-physiological features manifesting in single fundus images (e.g., optic nerve cupping) as well as fundus videos (e.g., vascular pulsatility index). Current convolutional neural networks (CNNs) developed to detect glaucoma are all based on spatial features embedded in an image. We developed a combined CNN and recurrent neural network (RNN) that not only extracts the spatial features in a fundus image but also the temporal features embedded in a fundus video (i.e., sequential images). A total of 1810 fundus images and 295 fundus videos were used to train a CNN and a combined CNN and Long Short-Term Memory RNN. The combined CNN/RNN model reached an average F-measure of 96.2% in separating glaucoma from healthy eyes. In contrast, the base CNN model reached an average F-measure of only 79.2%. This proof-of-concept study demonstrates that extracting spatial and temporal features from fundus videos using a combined CNN and RNN, can markedly enhance the accuracy of glaucoma detection.
Ghezelbash, F, Eskandari, AH, Shirazi-Adl, A, Kazempour, M, Tavakoli, J, Baghani, M & Costi, JJ 2021, 'Modeling of human intervertebral disc annulus fibrosus with complex multi-fiber networks', Acta Biomaterialia, vol. 123, pp. 208-221.
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Gil Aparicio, A & Valls Miro, J 2021, 'An Efficient Stochastic Constrained Path Planner for Redundant Manipulators', Applied Sciences, vol. 11, no. 22, pp. 10636-10636.
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This brief proposes a novel stochastic method that exploits the particular kinematics of mechanisms with redundant actuation and a well-known manipulability measure to track the desired end-effector task-space motion in an efficient manner. Whilst closed-form optimal solutions to maximise manipulability along a desired trajectory have been proposed in the literature, the solvers become unfeasible in the presence of obstacles. A manageable alternative to functional motion planning is thus proposed that exploits the inherent characteristics of null-space configurations to construct a generic solution able to improve manipulability along a task-space trajectory in the presence of obstacles. The proposed Stochastic Constrained Optimization (SCO) solution remains close to optimal whilst exhibiting computational tractability, being an attractive proposition for implementation on real robots, as shown with results in challenging simulation scenarios, as well as with a real 7R Sawyer manipulator, during surface conditioning tasks.
Gillovic, B, McIntosh, A, Cockburn-Wootten, C & Darcy, S 2021, 'Experiences of tourists with intellectual disabilities: A phenomenological approach', Journal of Hospitality and Tourism Management, vol. 48, pp. 155-162.
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This paper aims to explore ways in which adults with intellectual disabilities experience tourism. The study applies phenomenology and draws on in-depth interviews with participants with intellectual disabilities focusing on their lived experiences of tourism. The tourism experience was significant and meaningful to the participants, in that tourism provided a sense of ‘normality,’ encouraged self-efficacy, and strengthened relational connections. This paper advances theory by conceptualising the nature of the tourism experience through the authentic voices and lived experiences of adults with intellectual disabilities. This lens of intellectual disability addresses a scarcity of representation in existing tourism scholarship, augmenting and advancing inclusive understandings of tourism experiences for these individuals with disabilities.
Goodswen, SJ, Barratt, JLN, Kennedy, PJ, Kaufer, A, Calarco, L & Ellis, JT 2021, 'Machine learning and applications in microbiology', FEMS Microbiology Reviews, vol. 45, no. 5, p. fuab015.
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ABSTRACT To understand the intricacies of microorganisms at the molecular level requires making sense of copious volumes of data such that it may now be humanly impossible to detect insightful data patterns without an artificial intelligence application called machine learning. Applying machine learning to address biological problems is expected to grow at an unprecedented rate, yet it is perceived by the uninitiated as a mysterious and daunting entity entrusted to the domain of mathematicians and computer scientists. The aim of this review is to identify key points required to start the journey of becoming an effective machine learning practitioner. These key points are further reinforced with an evaluation of how machine learning has been applied so far in a broad scope of real-life microbiology examples. This includes predicting drug targets or vaccine candidates, diagnosing microorganisms causing infectious diseases, classifying drug resistance against antimicrobial medicines, predicting disease outbreaks and exploring microbial interactions. Our hope is to inspire microbiologists and other related researchers to join the emerging machine learning revolution.
Goodswen, SJ, Kennedy, PJ & Ellis, JT 2021, 'Applying Machine Learning to Predict the Exportome of Bovine and Canine Babesia Species That Cause Babesiosis', Pathogens, vol. 10, no. 6, pp. 660-660.
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Babesia infection of red blood cells can cause a severe disease called babesiosis in susceptible hosts. Bovine babesiosis causes global economic loss to the beef and dairy cattle industries, and canine babesiosis is considered a clinically significant disease. Potential therapeutic targets against bovine and canine babesiosis include members of the exportome, i.e., those proteins exported from the parasite into the host red blood cell. We developed three machine learning-derived methods (two novel and one adapted) to predict for every known Babesia bovis, Babesia bigemina, and Babesia canis protein the probability of being an exportome member. Two well-studied apicomplexan-related species, Plasmodium falciparum and Toxoplasma gondii, with extensive experimental evidence on their exportome or excreted/secreted proteins were used as important benchmarks for the three methods. Based on 10-fold cross validation and multiple train–validation–test splits of training data, we expect that over 90% of the predicted probabilities accurately provide a secretory or non-secretory indicator. Only laboratory testing can verify that predicted high exportome membership probabilities are creditable exportome indicators. However, the presented methods at least provide those proteins most worthy of laboratory validation and will ultimately save time and money.
Goodswen, SJ, Kennedy, PJ & Ellis, JT 2021, 'Computational Antigen Discovery for Eukaryotic Pathogens Using Vacceed', vol. 2183, pp. 29-42.
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© Springer Science+Business Media, LLC, part of Springer Nature 2021. Bioinformatics programs have been developed that exploit informative signals encoded within protein sequences to predict protein characteristics. Unfortunately, there is no program as yet that can predict whether a protein will induce a protective immune response to a pathogen. Nonetheless, predicting those pathogen proteins most likely from those least likely to induce an immune response is feasible when collectively using predicted protein characteristics. Vacceed is a computational pipeline that manages different standalone bioinformatics programs to predict various protein characteristics, which offer supporting evidence on whether a protein is secreted or membrane -associated. A set of machine learning algorithms predicts the most likely pathogen proteins to induce an immune response given the supporting evidence. This chapter provides step by step descriptions of how to configure and operate Vacceed for a eukaryotic pathogen of the user’s choice.
Grandou, C, Wallace, L, Coutts, AJ, Bell, L & Impellizzeri, FM 2021, 'Symptoms of Overtraining in Resistance Exercise: International Cross-Sectional Survey', International Journal of Sports Physiology and Performance, vol. 16, no. 1, pp. 80-89.
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Purpose: To provide details on the nature and symptomatic profile of training maladaptation in competitive resistance-based athletes to examine whether there are symptoms that may be used as prognostic indicators of overtraining. Identifying prognostic tools to assess for training maladaptation is essential for avoiding severe overtraining conditions. Methods: A Web-based survey was distributed to a cross-sectional convenience sample of competitive athletes involved in sports with a significant resistance-training component. The 46-item anonymous survey was distributed via industry experts and social media from July to August 2019. Results: The final sample included 605 responses (completion rate: 84%). About 71% of the respondents indicated that they had previously experienced an unexplained decrease in performance. Among those, the majority reported a performance decrement lasting 1 wk to 1 mo (43.8%). General feelings of fatigue were the most frequent self-reported symptom of maladaptation. Acute training maladaptation, lasting <1 mo, was also accompanied by symptoms of musculoskeletal aches and pain. In the majority of cases (92.5%), training maladaptation was accompanied by additional nontraining stressors. A greater proportion of the respondents with more severe maladaptation (>4 mo) were training to muscle failure. Conclusion: The results from this study support the multifactorial nature of training maladaptation. The multidimensional nature of fatigue and individual variability in symptomatic responses precludes definitive prognostic symptoms or differential diagnostic factors of functional/nonfunctional overreaching or the overtraining syndrome in resistance exercise.
Green, DW, Watson, JA, Ben-Nissan, B, Watson, GS & Stamboulis, A 2021, 'Synthetic tissue engineering with smart, cytomimetic protocells', Biomaterials, vol. 276, pp. 120941-120941.
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Gupta, G, Chellappan, DK, Singh, SK, Gupta, PK, Kesari, KK, Jha, NK, Thangavelu, L, G Oliver, B & Dua, K 2021, 'Advanced drug delivery approaches in managing TGF-β-mediated remodeling in lung diseases', Nanomedicine, vol. 16, no. 25, pp. 2243-2247.
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Haeusler, GM, De Abreu Lourenco, R, Bakos, C, O'Brien, T, Slavin, MA, Clark, JE, McMullan, B, Borland, ML, Babl, FE, Krishnasamy, M, Vanevski, M, Thursky, KA & Hall, L 2021, 'Managing low‐risk febrile neutropenia in children in the time of COVID‐19: What matters to parents and clinicians', Journal of Paediatrics and Child Health, vol. 57, no. 6, pp. 826-834.
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AimThe Australian ‘There is no place like home’ project is implementing a paediatric low‐risk febrile neutropenia (FN) programme across eight paediatric hospitals. We sought to identify the impact of the coronavirus disease 2019 (COVID‐19) pandemic on programme implementation.MethodsPaediatric oncology, infectious diseases and emergency medicine health‐care workers and parent/carers were surveyed to explore the impact of the COVID‐19 pandemic on home‐based FN care. Online surveys were distributed nationally to health‐care workers involved in care of children with FN and to parents or carers of children with cancer.ResultsSurveys were completed by 78 health‐care workers and 32 parents/carers. Overall, 95% of health‐care workers had confidence in the safety of home‐based FN care, with 35% reporting changes at their own hospitals in response to the pandemic that made them more comfortable with this model. Compared to pre‐pandemic, >50% of parent/carers were now more worried about attending the hospital with their child and >80% were interested in receiving home‐based FN care. Among both groups, increased telehealth access and acceptance of home‐based care, improved patient quality of life and reduced risk of nosocomial infection were identified as programme enablers, while re‐direction of resources due to COVID‐19 and challenges in implementing change during a crisis were potential barriers.ConclusionThere is strong clinician and parent/carer support for home‐based management of low‐risk FN across Australia. Changes made to the delivery of cancer care in response to the pandemic have generally increased acceptance for home‐based treatments and opportunities exist to leverage these to refine the low‐risk FN programme.
Haeusler, GM, De Abreu Lourenco, R, Clark, H, Thursky, KA, Slavin, MA, Babl, FE, Mechinaud, F, Alvaro, F, Clark, J, Padhye, B, Phillips, M, Super, L, Tapp, H, Walwyn, T, Ziegler, D, Phillips, R & Worth, LJ 2021, 'Diagnostic Yield of Initial and Consecutive Blood Cultures in Children With Cancer and Febrile Neutropenia', Journal of the Pediatric Infectious Diseases Society, vol. 10, no. 2, pp. 125-130.
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Abstract Background The timing and necessity of repeated blood cultures (BCs) in children with cancer and febrile neutropenia (FN) are unknown. We evaluated the diagnostic yield of BCs collected pre- and post-empiric FN antibiotics. Methods Data collected prospectively from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) study were used. Diagnostic yield was calculated as the number of FN episodes with a true bloodstream infection (BSI) detected divided by the number of FN episodes that had a BC taken. Results A BSI was identified in 13% of 858 FN episodes. The diagnostic yield of pre-antibiotic BCs was higher than of post-antibiotic cultures (12.3% vs 4.4%, P < .001). Two-thirds of the post-antibiotic BSIs were associated with a new episode of fever or clinical instability, and only 2 new BSIs were identified after 48 hours of empiric antibiotics and persistent fever. A contaminated BC was identified more frequently in post-antibiotic cultures. Conclusions In the absence of new fever or clinical instability, BCs beyond 48 hours of persistent fever have limited yield. Opportunity exists to optimize BC collection in this population and reduce the burden of unnecessary tests on patients, healthcare workers, and hospitals.
Haeusler, GM, Gaynor, L, Teh, B, Babl, FE, Orme, LM, Segal, A, Mechinaud, F, Bryant, PA, Phillips, B, Lourenco, RDA, Slavin, MA & Thursky, KA 2021, 'Home-based care of low-risk febrile neutropenia in children—an implementation study in a tertiary paediatric hospital', Supportive Care in Cancer, vol. 29, no. 3, pp. 1609-1617.
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Han, YY, Zhang, X, Wang, J, Wang, G, Oliver, BG, Zhang, HP, Kang, DY, Wang, L, Qiu, ZX, Li, WM & Wang, G 2021, 'Multidimensional Assessment of Asthma Identifies Clinically Relevant Phenotype Overlap: A Cross-Sectional Study', The Journal of Allergy and Clinical Immunology: In Practice, vol. 9, no. 1, pp. 349-362.e18.
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BACKGROUND:Asthma is a heterogeneous disease with multiple phenotypes; however, the relevance of phenotype overlap remains largely unexplored. OBJECTIVE:To examine the relationship between phenotype overlap and clinical and inflammatory profiles of asthma. METHODS:In this cross-sectional study, adult participants with stable asthma (n = 522) underwent multidimensional assessments. The 10 most common phenotypes of asthma were defined and then classified into those commonly associated with Type (T) 2 or non-T2 inflammation. Furthermore, phenotype overlap scores (POS), representing the cumulative concomitant phenotypes, were used to analyze its association with clinical and inflammatory asthmatic profiles. RESULTS:Among the 522 participants, 73.4% (n = 383) had phenotype overlap, and mixed T2 and non-T2 inflammation coexisted in 47.5% (n = 248). T2 POS was positively associated with eosinophils, IgE, and fractional exhaled nitric oxide (FeNO), and negatively with Asthma Quality of Life Questionnaire (AQLQ), sputum neutrophils, IL-17A, IL-8, and TNF-α. Non-T2 POS was positively associated with Asthma Control Questionnaire, neutrophils and sputum IL-8, and negatively with AQLQ, forced expiratory volume in 1 s, blood eosinophils, IgE, and FeNO (all P < .05). Patients with phenotypes that are associated with mixed T2 and non-T2 inflammation had elevated T2 inflammation biomarkers but worse asthma control. Both T2 (adjusted β = -0.191, P = .035) and non-T2 (adjusted β = 0.310, P < .001) POS were significantly associated with severe exacerbations. CONCLUSIONS:Phenotype overlap is extremely common in asthmatic patients and significantly associated with clinical and inflammatory profiles. Patients with phenotypes associated with mixed T2 and non-T2 inflammation might be unresponsive to medications owing to increased non-T2 inflammation. Multidimensional asthma assessment identifies clinically relevant phenotype overlap.
Harley, W, Yoshie, H & Gentile, C 2021, 'Three-Dimensional Bioprinting for Tissue Engineering and Regenerative Medicine in Down Under: 2020 Australian Workshop Summary', ASAIO Journal, vol. 67, no. 4, pp. 363-369.
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He, F, Huang, X, Wang, X, Qiu, S, Jiang, F & Ling, SH 2021, 'A neuron image segmentation method based Deep Boltzmann Machine and CV model', Computerized Medical Imaging and Graphics, vol. 89, pp. 101871-101871.
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Henderson, MJ, Chrismas, BCR, Stevens, CJ, Fransen, J, Coutts, AJ & Taylor, L 2021, 'Limiting Rise in Heat Load With an Ice Vest During Elite Female Rugby Sevens Warm-Ups', International Journal of Sports Physiology and Performance, vol. 16, no. 11, pp. 1684-1691.
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Purpose: To determine the effect of wearing a phase-change cooling vest in elite female rugby sevens athletes during (1) a simulated match-day warm-up in hot conditions prior to a training session and (2) a prematch warm-up during a tournament in cool conditions. Methods: This study consisted of 2 randomized independent group designs (separated by 16 d) where athletes completed the same 23- to 25-minute match-day warm-up (1) in hot conditions (range = 28.0°C to 35.1°C wet bulb globe temperature [WBGT]) prior to training and (2) in cool conditions (range = 18.8°C to 20.1°C WBGT) prior to a World Rugby Women’s Sevens Series match. In both conditions, athletes were randomly assigned to wearing either (1) the standardized training/playing ensemble (synthetic rugby shorts and training tee/jersey) or (2) the standardized training/playing ensemble plus a commercial phase-change athletic cooling vest. Group-wise differences in core temperature rise from baseline, global positioning system–measured external locomotive output, and perceptual thermal load were compared. Results: Core temperature rise during a match warm-up was lower in the hot condition only (−0.65°C [95% confidence interval = −1.22°C to −0.08°C], [95% confidence interval = .00 to .51], P = .028). No differences in various external-load variables were observed. Conclusions: Phase-change cooling vests can be worn by athletes prior to, and during, a prematch warm-up in hot conditions to limit excess core temperature rise without adverse effects on thermal perceptions or external locomotion output.
Henderson, MJ, Chrismas, BCR, Stevens, CJ, Novak, A, Fransen, J, Coutts, AJ & Taylor, L 2021, 'Additional Clothing Increases Heat Load in Elite Female Rugby Sevens Players', International Journal of Sports Physiology and Performance, vol. 16, no. 10, pp. 1424-1431.
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Purpose: To determine whether elite female rugby sevens players are exposed to core temperatures (Tc) during training in the heat that replicate the temperate match demands previously reported and to investigate whether additional clothing worn during a hot training session meaningfully increases the heat load experienced. Methods: A randomized parallel-group study design was employed, with all players completing the same approximately 70-minute training session (27.5°C–34.8°C wet bulb globe temperature) and wearing a standardized training ensemble (synthetic rugby shorts and training tee [control (CON); n = 8]) or additional clothing (standardized training ensemble plus compression garments and full tracksuit [additional clothing (AC); n = 6]). Groupwise differences in Tc, sweat rate, GPS-measured external locomotive output, rating of perceived exertion, and perceptual thermal load were compared. Results: Mean (P = .006, ) and peak (P < .001, ) Tc were higher in AC compared with CON during the training session. There were no differences in external load (F4,9 = 0.155, P = .956, Wilks Λ = 0.935, ) or sweat rate (P = .054, Cohen d = 1.09). A higher rating of perceived exertion (P = .016, Cohen d = 1.49) was observed in AC compared with CON. No exertional-heat-illness symptomology was reported in either group. Conclusions: Player Tc is similar between training performed in hot environments and match play in temperate conditions when involved for &g...
Herath, S, Sadeghi Rad, H, Radfar, P, Ladwa, R, Warkiani, M, O’Byrne, K & Kulasinghe, A 2021, 'The Role of Circulating Biomarkers in Lung Cancer', Frontiers in Oncology, vol. 11, p. 801269.
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Lung cancer is the leading cause of cancer morbidity and mortality worldwide and early diagnosis is crucial for the management and treatment of this disease. Non-invasive means of determining tumour information is an appealing diagnostic approach for lung cancers as often accessing and removing tumour tissue can be a limiting factor. In recent years, liquid biopsies have been developed to explore potential circulating tumour biomarkers which are considered reliable surrogates for understanding tumour biology in a non-invasive manner. Most common components assessed in liquid biopsy include circulating tumour cells (CTCs), cell-free DNA (cfDNA), circulating tumour DNA (ctDNA), microRNA and exosomes. This review explores the clinical use of circulating tumour biomarkers found in liquid biopsy for screening, early diagnosis and prognostication of lung cancer patients.
Hesamian, MH, Jia, W, He, X, Wang, Q & Kennedy, PJ 2021, 'Synthetic CT images for semi-sequential detection and segmentation of lung nodules', Applied Intelligence, vol. 51, no. 3, pp. 1616-1628.
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© 2020, Springer Science+Business Media, LLC, part of Springer Nature. Accurately detecting and segmenting lung nodules from CT images play a critical role in the earlier diagnosis of lung cancer and thus have attracted much interest from the research community. However, due to the irregular shapes of nodules, and the low-intensity contrast between the nodules and other lung areas, precisely segmenting nodules from lung CT images is a very challenging task. In this paper, we propose a highly effective and robust solution to this problem by innovatively utilizing the changes of nodule shapes over continuous slices (inter-slice changes) and develop a deep learning based end-to-end system. Different from the existing 2.5D or 3D methods that attempt to explore the inter-slice features, we propose to create a novel synthetic image to depict the unique changing pattern of nodules between slices in distinctive colour patterns. Based on the new synthetic images, we then adopt the deep learning based image segmentation techniques and develop a modified U-Net architecture to learn the unique color patterns formed by nodules. With our proposed approach, the detection and segmentation of nodules can be achieved simultaneously with an accuracy significantly higher than the state of the arts by 10% without introducing high computation cost. By taking advantage of inter-slice information and form the proposed synthetic image, the task of lung nodule segmentation is done more accurately and effectively.
Hickey, BA, Chalmers, T, Newton, P, Lin, C-T, Sibbritt, D, McLachlan, CS, Clifton-Bligh, R, Morley, J & Lal, S 2021, 'Smart Devices and Wearable Technologies to Detect and Monitor Mental Health Conditions and Stress: A Systematic Review', Sensors, vol. 21, no. 10, pp. 3461-3461.
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Recently, there has been an increase in the production of devices to monitor mental health and stress as means for expediting detection, and subsequent management of these conditions. The objective of this review is to identify and critically appraise the most recent smart devices and wearable technologies used to identify depression, anxiety, and stress, and the physiological process(es) linked to their detection. The MEDLINE, CINAHL, Cochrane Central, and PsycINFO databases were used to identify studies which utilised smart devices and wearable technologies to detect or monitor anxiety, depression, or stress. The included articles that assessed stress and anxiety unanimously used heart rate variability (HRV) parameters for detection of anxiety and stress, with the latter better detected by HRV and electroencephalogram (EGG) together. Electrodermal activity was used in recent studies, with high accuracy for stress detection; however, with questionable reliability. Depression was found to be largely detected using specific EEG signatures; however, devices detecting depression using EEG are not currently available on the market. This systematic review highlights that average heart rate used by many commercially available smart devices is not as accurate in the detection of stress and anxiety compared with heart rate variability, electrodermal activity, and possibly respiratory rate.
Hoang, DK, Le, NM, Vo‐Thi, UP, Nguyen, HG, Ho‐Pham, LT & Nguyen, TV 2021, 'Mechanography assessment of fall risk in older adults: the Vietnam Osteoporosis Study', Journal of Cachexia, Sarcopenia and Muscle, vol. 12, no. 5, pp. 1161-1167.
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AbstractBackgroundJumping mechanography is a technology for quantitatively assessing muscular function and balance in older adults. This study sought to define the association between jumping mechanography parameters and fall risk in Vietnamese individuals.MethodsThe study involved 375 women and 244 men aged 50 years and older, who were recruited from the general population in Ho Chi Minh City (Vietnam). The individuals had been followed for 2 years. At baseline, Esslinger Fitness index (EFI), jumping power, force, velocity of lower limbs, and the ability to maintain balance were measured by a Leonardo Mechanograph Ground Reaction Force system (Novotec Medical, Pforxheim, Germany). The incidence of falls during the follow‐up period was ascertained from self‐report. Logistic regression analysis was used to analyse the association between jumping mechanography parameters and fall risk.ResultsThe average age of participants at baseline was 56.7 years (SD 5.85). During the 2 year follow‐up, 92 falls were reported, making the incidence of fall at ~15% [95% confidence interval (CI), 12.1 to 18.2]. The incidence of fall increased with advancing age, and women had a higher incidence than men (17.6% vs. 10.7%; P = 0.024). In univariate analysis, maximal velocity [odds ratio (OR) 0.65; 95% CI, 0.52 to 0.82], maximal force (OR 0.83; 95% CI, 0.65 to 1.04), and maximal power (OR 0.68; 95% CI, 0.52 to 0.88) were each significantly associated with fall risk. EFI was not significantly associated with fall risk (OR 1.09; 95% CI, 0.86 to 1.39). However, in a multiple logistic regression model, greater maximum velocity was associated with lower odds of fall (OR 0.38; 95% CI, 0.16 to 0.92).Conclusions<...
Ho-Le, TP, Tran, HTT, Center, JR, Eisman, JA, Nguyen, HT & Nguyen, TV 2021, 'Assessing the clinical utility of genetic profiling in fracture risk prediction: a decision curve analysis', Osteoporosis International, vol. 32, no. 2, pp. 271-280.
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Using decision curve analysis on 2188 women and 1324 men, we found that an osteogenomic profile constructed from 62 genetic variants improved the clinical net benefit of fracture risk prediction over and above that of clinical risk factors and BMD.
Introduction
Genetic profiling is a promising tool for assessing fracture risk. This study sought to use the decision curve analysis (DCA), a novel approach to determine the impact of genetic profiling on fracture risk prediction.Methods
The study involved 2188 women and 1324 men, aged 60 years and above, who were followed for up to 23 years. Bone mineral density (BMD) and clinical risk factors were obtained at baseline. The incidence of fracture and mortality were recorded. A weighted individual genetic risk score (GRS) was constructed from 62 BMD-associated genetic variants. Four models were considered: CRF (clinical risk factors); CRF + GRS; Garvan model (GFRC) including CRF and femoral neck BMD; and GFRC + GRS. The DCA was used to evaluate the clinical net benefit of predictive models at a range of clinically reasonable risk thresholds.Results
In both women and men, the full model GFRC + GRS achieved the highest net benefits. For 10-year risk threshold > 18% for women and > 15% for men, the GRS provided net benefit above those of the CRF models. At 20% risk threshold, adding the GRS could help to avoid 1 additional treatment per 81 women or 1 per 24 men compared with the Garvan model. At lower risk thresholds, there was no significant difference between the four models.Conclusions
The addition of genetic profiling into the clinical risk factors can improve the net clinical benefit at higher risk thresholds of fracture. Although the contribution of genetic profiling was modest in the presence of BMD + CRF, it appeared to be able to replace BMD for fracture prediction.
Ho-Le, TP, Tran, TS, Bliuc, D, Pham, HM, Frost, SA, Center, JR, Eisman, JA & Nguyen, TV 2021, 'Epidemiological transition to mortality and refracture following an initial fracture', eLife, vol. 10, pp. 1-15.
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This study sought to redefine the concept of fracture risk that includes refracture and mortality, and to transform the risk into 'skeletal age'. We analysed data obtained from 3521 women and men aged 60 years and older, whose fracture incidence, mortality, and bone mineral density (BMD) have been monitored since 1989. During the 20-year follow-up period, among 632 women and 184 men with a first incident fracture, the risk of sustaining a second fracture was higher in women (36%) than in men (22%), but mortality risk was higher in men (41%) than in women (25%). The increased risk of mortality was not only present with an initial fracture, but was accelerated with refractures. Key predictors of post-fracture mortality were male gender (hazard ratio [HR] 2.4; 95% CI, 1.79–3.21), advancing age (HR 1.67; 1.53–1.83), and lower femoral neck BMD (HR 1.16; 1.01–1.33). A 70-year-old man with a fracture is predicted to have a skeletal age of 75. These results were incorporated into a prediction model to aid patient-doctor discussion about fracture vulnerability and treatment decisions.
Hosie, A, Agar, M, Caplan, GA, Draper, B, Hedger, S, Rowett, D, Tuffin, P, Cheah, SL, Phillips, JL, Brown, L, Sidhu, M & Currow, DC 2021, 'Clinicians’ delirium treatment practice, practice change, and influences: A national online survey', Palliative Medicine, vol. 35, no. 8, pp. 1553-1563.
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Background: Recent studies cast doubt on the net effect of antipsychotics for delirium. Aim: To investigate the influence of these studies and other factors on clinicians’ delirium treatment practice and practice change in palliative care and other specialties using the Theoretical Domains Framework. Design: Australia-wide online survey of relevant clinicians. Setting/participants: Registered nurses (72%), doctors (16%), nurse practitioners (6%) and pharmacists (5%) who cared for patients with delirium in diverse settings, recruited through health professionals’ organisations. Results: Most of the sample ( n = 475): worked in geriatrics/aged (31%) or palliative care (30%); in hospitals (64%); and saw a new patient with delirium at least weekly (61%). More (59%) reported delirium practice change since 2016, mostly by increased non-pharmacological interventions (53%). Fifty-five percent reported current antipsychotic use for delirium, primarily for patient distress (79%) and unsafe behaviour (67%). Common Theoretical Domains Framework categories of influences on respondents’ delirium practice were: emotion (54%); knowledge (53%) and physical (43%) and social (21%) opportunities. Palliative care respondents more often reported: awareness of any named key study of antipsychotics for delirium (73% vs 39%, p < 0.001); changed delirium treatment (73% vs 53%, p = 0.017); decreased pharmacological interventions (60% vs 15%, p < 0.001); off-label medication use (86% vs 51%, p < 0.001: antipsychotics 79% vs 44%, p < 0.001; benzodiazepines 61% vs 26%, p < 0.001) and emotion as an influence (82% vs 39%, p < 0.001). Co...
Hossain, I, Zhou, S, Ishac, K, Lind, E, Sharwood, L & Eager, D 2021, 'A Measurement of ‘Walking-the-Wall’ Dynamics: An Observational Study Using Accelerometry and Sensors to Quantify Risk Associated with Vertical Wall Impact Attenuation in Trampoline Parks', Sensors, vol. 21, no. 21, pp. 7337-7337.
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This study illustrates the application of a tri-axial accelerometer and gyroscope sensor device on a trampolinist performing the walking-the-wall manoeuvre on a high-performance trampoline to determine the performer dynamic conditions. This research found that rigid vertical walls would allow the trampolinist to obtain greater control and retain spatial awareness at greater levels than what is achievable on non-rigid vertical walls. With a non-rigid padded wall, the reaction force from the wall can be considered a variable force that is not constrained, and would not always provide the feedback that the trampolinist needs to maintain the balance with each climb up the wall and fall from height. This research postulates that unattenuated vertical walls are safer than attenuated vertical walls for walking-the-wall manoeuvres within trampoline park facilities. This is because non-rigid walls would provide higher g-force reaction feedback from the wall, which would reduce the trampolinist’s control and stability. This was verified by measuring g-force on a horizontal rigid surface versus a non-rigid surface, where the g-force feedback was 27% higher for the non-rigid surface. Control and stability are both critical while performing the complex walking-the-wall manoeuvre. The trampolinist experienced a very high peak g-force, with a maximum g-force of approximately 11.5 g at the bottom of the jump cycle. It was concluded that applying impact attenuation padding to vertical walls used for walking-the-wall and similar activities would increase the likelihood of injury; therefore, padding of these vertical surfaces is not recommended.
Huang, T, Yang, M, Zeng, Y, Huang, X, Wang, N, Chen, Y, Li, P, Yuan, J, Chen, C, Oliver, BG & Yi, C 2021, 'Maternal High Fat Diet Consumption Exaggerates Metabolic Disorders in Mice With Cigarette-Smoking Induced Intrauterine Undernutrition', Frontiers in Nutrition, vol. 8, p. 638576.
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Objectives: Maternal smoking causes fetal underdevelopment and results in births which are small for gestation age due to intrauterine undernutrition, leading to various metabolic disorders in adulthood. Furthermore, postnatal high fat diet (HFD) consumption is also a potent obesogenic factor, which can interact with maternal smoking. In this study, we aimed to determine whether maternal HFD consumption during pregnancy can reverse the adverse impact of maternal smoking and change the response to postnatal HFD consumption.Methods: Female mice were exposed to cigarette smoke (SE, 2 cigarettes/day) or sham exposed for 5 weeks before mating, with half of the SE dams fed HFD (43% fat, SE+HFD). The same treatment continued throughout gestation and lactation. Male offspring from each maternal group were fed the same HFD or chow after weaning and sacrificed at 13 weeks.Results: Maternal SE alone increased body weight and fat mass in HFD-fed offspring, while SE+HFD offspring showed the highest energy intake and glucose metabolic disorder in adulthood. In addition, postnatal HFD increased the body weight and aggravated the metabolic disorder caused by maternal SE and SE+HFD.Conclusions: Maternal HFD consumption could not ameliorate the adverse effect of maternal SE but exaggerate metabolic disorders in adult offspring. Smoking cessation and a healthy diet are needed during pregnancy to optimize the health outcome in the offspring.
Huang, T, Zhang, Y, Wang, Z, Zeng, Y, Wang, N, Fan, H, Huang, Z, Su, Y, Huang, X, Chen, H, Zhang, K & Yi, C 2021, 'Optogenetically Controlled TrkA Activity Improves the Regenerative Capacity of Hair‐Follicle‐Derived Stem Cells to Differentiate into Neurons and Glia', Advanced Biology, vol. 5, no. 5, pp. e2000134-2000134.
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AbstractHair‐follicle‐derived stem cells (HSCs) originating from the bulge region of the mouse vibrissa hair follicle are able to differentiate into neuronal and glial lineage cells. The tropomyosin receptor kinase A (TrkA) receptor that is expressed on these cells plays key roles in mediating the survival and differentiation of neural progenitors as well as in the regulation of the growth and regeneration of different neural systems. In this study, the OptoTrkA system is introduced, which is able to stimulate TrkA activity via blue‐light illumination in HSCs. This allows to determine whether TrkA signaling is capable of influencing the proliferation, migration, and neural differentiation of these somatic stem cells. It is found that OptoTrkA is able to activate downstream molecules such as ERK and AKT with blue‐light illumination, and subsequently able to terminate this kinase activity in the dark. HSCs with OptoTrkA activity show an increased ability for proliferation and migration and also exhibited accelerated neuronal and glial cell differentiation. These findings suggest that the precise control of TrkA activity using optogenetic tools is a viable strategy for the regeneration of neurons from HSCs, and also provides a novel insight into the clinical application of optogenetic tools in cell‐transplantation therapy.
Huang, X, Cai, H, Li, H, Su, Y, Li, H, Li, W, Yi, C, Oliver, BG & Chen, H 2021, 'Cinnamon as Dietary Supplement Caused Hyperlipidemia in Healthy Rats', Evidence-Based Complementary and Alternative Medicine, vol. 2021, pp. 1-7.
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Objective. Cinnamon is a cooking spice and a medicinal herb. It is increasingly used as a health supplement due to its perceived benefit to prevent and or manage type 2 diabetes and metabolic disorders. However, it is unclear if regular consumption of this medicinal plant will interfere with normal physiological functions. Therefore, this study investigated the impact of daily cinnamon supplements on glucose and lipid metabolic profiles in healthy rats. Methods. Male rats (Sprague Dawley, 8 weeks) were supplied with cinnamon in their diet (equivalent to ∼1 g/day in humans) for two weeks. Blood glucose and lipid levels, as well as metabolic markers in both liver and abdominal white adipose tissue, were measured. Results. Cinnamon significantly increased fat mass and blood cholesterol and low-density lipoprotein (LDL) levels, but reduced fasting blood glucose level by 12%. Liver functional enzymes were normal in rats consuming cinnamon. However, several lipid metabolic markers were impaired which may contribute to dyslipidemia, including two main switches for energy metabolism (sirtuin 1 and peroxisome proliferator-activated receptor-gamma coactivator-1α) and the LDL receptor. However, de novo lipid synthesis enzymes and inflammatory markers were also reduced in the liver by cinnamon treatment, which may potentially prevent the development of steatosis. Markers for lipid oxidation were downregulated in fat tissue in cinnamon-treated rats, contributing to increased fat accumulation. Conclusion. Daily low-dose cinnamon supplementation seems to promote abdominal adipose tissue accumulation and disturb lipid homeostasis in healthy rats, raising the concerns regarding daily use in healthy people.
Huang, X, Su, Y, Wang, N, Li, H, Li, Z, Yin, G, Chen, H, Niu, J & Yi, C 2021, 'Astroglial Connexins in Neurodegenerative Diseases', Frontiers in Molecular Neuroscience, vol. 14.
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Astrocytes play a crucial role in the maintenance of the normal functions of the Central Nervous System (CNS). During the pathogenesis of neurodegenerative diseases, astrocytes undergo morphological and functional remodeling, a process called reactive astrogliosis, in response to the insults to the CNS. One of the key aspects of the reactive astrocytes is the change in the expression and function of connexins. Connexins are channel proteins that highly expressed in astrocytes, forming gap junction channels and hemichannels, allowing diffusional trafficking of small molecules. Alterations of astrocytic connexin expression and function found in neurodegenerative diseases have been shown to affect the disease progression by changing neuronal function and survival. In this review, we will summarize the role of astroglial connexins in neurodegenerative diseases including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Also, we will discuss why targeting connexins can be a plausible therapeutic strategy to manage these neurodegenerative diseases.
Huang, Y, Song, R, Argha, A, Celler, BG, Savkin, AV & Su, SW 2021, 'Human Motion Intent Description Based on Bumpless Switching Mechanism for Rehabilitation Robot', IEEE Transactions on Neural Systems and Rehabilitation Engineering, vol. 29, pp. 673-682.
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Huo, L, Jiao Li, J, Chen, L, Yu, Z, Hutvagner, G & Li, J 2021, 'Single-cell multi-omics sequencing: application trends, COVID-19, data analysis issues and prospects', Briefings in Bioinformatics, vol. 22, no. 6, p. bbab229.
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AbstractSingle-cell sequencing is a biotechnology to sequence one layer of genomic information for individual cells in a tissue sample. For example, single-cell DNA sequencing is to sequence the DNA from every single cell. Increasing in complexity, single-cell multi-omics sequencing, or single-cell multimodal omics sequencing, is to profile in parallel multiple layers of omics information from a single cell. In practice, single-cell multi-omics sequencing actually detects multiple traits such as DNA, RNA, methylation information and/or protein profiles from the same cell for many individuals in a tissue sample. Multi-omics sequencing has been widely applied to systematically unravel interplay mechanisms of key components and pathways in cell. This survey overviews recent developments in single-cell multi-omics sequencing, and their applications to understand complex diseases in particular the COVID-19 pandemic. We also summarize machine learning and bioinformatics techniques used in the analysis of the intercorrelated multilayer heterogeneous data. We observed that variational inference and graph-based learning are popular approaches, and Seurat V3 is a commonly used tool to transfer the missing variables and labels. We also discussed two intensively studied issues relating to data consistency and diversity and commented on currently cared issues surrounding the error correction of data pairs and data imputation methods. The survey is concluded with some open questions and opportunities for this extraordinary field.
Hussain, MS, Sharma, P, Dhanjal, DS, Khurana, N, Vyas, M, Sharma, N, Mehta, M, Tambuwala, MM, Satija, S, Sohal, SS, Oliver, BGG & Sharma, HS 2021, 'Nanotechnology based advanced therapeutic strategies for targeting interleukins in chronic respiratory diseases', Chemico-Biological Interactions, vol. 348, pp. 109637-109637.
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Both communicable and non-communicable chronic respiratory conditions have accorded for suffering of millions of people of all ages and stated to be leading cause of death, morbidity, economic and social pressures, and disability-adjusted life-years (DALYs) worldwide. These illnesses impair patient's health and negatively impacts families and society, particularly in low and middle-income countries. Chronic respiratory diseases (CRDs) affect different organs of respiratory system, involving airways, parenchyma, and pulmonary vasculature. As the number of respiratory diseases are exponentially escalating but still the stakeholders are not paying attention towards its serious complications. Currently, the treatment being used primarily focusses only on alleviating symptoms of these illness rather delivering the therapeutic agent at target site for optimal care and/or prevention. Lately, extensive research is being conducted on airways and systemic inflammation, oxidative stress, airway, or parenchymal rehabilitation. From which macrophages, neutrophils, and T cells, as well as structural cells as fibroblasts, epithelial, endothelial, and smooth muscle cells have been found to be active participants that are involved in these chronic respiratory diseases. The pathogenesis of all these chronic respiratory diseases gets caused differently via mediators and proteins, including cytokines, chemokines, growth factors and oxidants. Presently, the target of prescription therapies is to reduce the inflammation of airways and relieve the airway contraction. In all studies, cytokines have been found to play an imperative role in fostering chronic airway inflammation and remodelling. Owing to the limitations of conventional treatments, the current review aims to summarize the current knowledge about the chronic respiratory disease and discuss further about the various conventional methods that can be used for treating this ailment. Additionally, it also highlights and...
Impellizzeri, FM, Woodcock, S, Coutts, AJ, Fanchini, M, McCall, A & Vigotsky, AD 2021, 'What Role Do Chronic Workloads Play in the Acute to Chronic Workload Ratio? Time to Dismiss ACWR and Its Underlying Theory', Sports Medicine, vol. 51, no. 3, pp. 581-592.
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Aim
The aim of this study was to examine the associations between the injury risk and the acute (AL) to chronic (CL) workload ratio (ACWR) by substituting the original CL with contrived values to assess the role of CL (i.e., the presence and implications of statistical artefacts).Methods
Using previously published data, we generated a contrived ACWR by dividing the AL by fixed and randomly generated CLs, and we compared these results to real data. We also reproduced previously reported subgroup analyses, including dichotomising players' data above and below the median CL. Our analyses follow the same, previously published modelling approach.Results
The analyses with original data showed effects compatible with higher injury risk for ACWR only (odd ratios, OR: 2.45, 95% CI 1.28-4.71). However, we observed similar effects by dividing AL by the 'contrived' fixed and randomly generated CLs: OR 1.95 (1.18-3.52) dividing by 1510 (average CL); and OR ranging from 1.16 to 2.07, using random CL 1.53 (mean). Random ACWRs reduced the variance relative to the original AL and further inflated the ORs (mean OR 1.89, from 1.42 to 2.70). ACWR causes artificial reclassification of players compared to AL alone. Finally, neither ACWR nor AL alone confer a meaningful predictive advantage to an intercept-only model, even within the training sample (c-statistic 0.574/0.544 vs. 0.5 in both ACWR/AL and intercept-only models, respectively).Discussion
ACWR is a rescaling of the explanatory variable (AL, numerator), in turn magnifying its effect estimates and decreasing its variance despite conferring no predictive advantage. Other ratio-related transformations (e.g., reducing the variance of the explanatory variable and unjustified reclassifications) further inflate the OR of AL alone with injury risk. These results also disprove the etiological theory behind this ratio and its components. We suggest ACWR be dismissed as a framework and model, and...
Ishac, K & Eager, D 2021, 'Evaluating Martial Arts Punching Kinematics Using a Vision and Inertial Sensing System', Sensors, vol. 21, no. 6, pp. 1948-1948.
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Martial arts has many benefits not only in self-defence, but also in improving physical fitness and mental well-being. In our research we focused on analyzing the velocity, impulse, momentum and impact force of the Taekwondo sine-wave punch and reverse-step punch. We evaluated these techniques in comparison with the martial arts styles of Hapkido and Shaolin Wushu and investigated the kinematic properties. We developed a sensing system which is composed of an ICSensor Model 3140 accelerometer attached to a punching bag for measuring dynamic acceleration, Kinovea motion analysis software and 2 GoPro Hero 3 cameras, one focused on the practitioner’s motion and the other focused on the punching bag’s motion. Our results verified that the motion vectors associated with a Taekwondo practitioner performing a sine-wave punch, uses a unique gravitational potential energy to optimise the impact force of the punch. We demonstrated that the sine-wave punch on average produced an impact force of 6884 N which was higher than the reverse-step punch that produced an average impact force of 5055 N. Our comparison experiment showed that the Taekwondo sine-wave punch produced the highest impact force compared to a Hapkido right cross punch and a Shaolin Wushu right cross, however the Wushu right cross had the highest force to weight ratio at 82:1. The experiments were conducted with high ranking black belt practitioners in Taekwondo, Hapkido and Shaolin Wushu.
Italiano, CJ, Pu, L, Violi, JP, Duggin, IG & Rodgers, KJ 2021, 'Cysteine biosynthesis contributes to β-methylamino-l-alanine tolerance in Escherichia coli', Research in Microbiology, vol. 172, no. 6, pp. 103852-103852.
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In contrast to mammalian cells, bacteria such as Escherichia coli have been shown to display tolerance towards the neurotoxin β-methylamino-l-alanine (BMAA) suggesting that these prokaryotes possess a way to metabolise BMAA or its products, resulting in their export, degradation, or detoxification. Single gene deletion mutants of E. coli K-12 with inactivated amino acid biosynthesis pathways were treated with 500 μg/ml BMAA and the resulting growth was monitored. Wild type E. coli and most of the gene deletion mutants displayed unaltered growth in the presence of BMAA over 12 h. Conversely, deletion of genes in the cysteine biosynthesis pathway, cysE, cysK or cysM resulted in a BMAA dose-dependent growth delay in minimal medium. Through further studies of the ΔcysE strain, we observed increased susceptibility to oxidative stress from H2O2 in minimal medium, and disruptions in glutathione levels and oxidation state. The cysteine biosynthesis pathway is therefore linked to the tolerance of BMAA and oxidative stress in E. coli, which potentially represents a mechanism of BMAA detoxification.
Iuliano, S, Poon, S, Robbins, J, Bui, M, Wang, X, De Groot, L, Van Loan, M, Zadeh, AG, Nguyen, T & Seeman, E 2021, 'Effect of dietary sources of calcium and protein on hip fractures and falls in older adults in residential care: cluster randomised controlled trial', BMJ, vol. 375, pp. n2364-n2364.
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AbstractObjectiveTo assess the antifracture efficacy and safety of a nutritional intervention in institutionalised older adults replete in vitamin D but with mean intakes of 600 mg/day calcium and <1 g/kg body weight protein/day.DesignTwo year cluster randomised controlled trial.Setting60 accredited residential aged care facilities in Australia housing predominantly ambulant residents.Participants7195 permanent residents (4920 (68%) female; mean age 86.0 (SD 8.2) years).InterventionFacilities were stratified by location and organisation, with 30 facilities randomised to provide residents with additional milk, yoghurt, and cheese that contained 562 (166) mg/day calcium and 12 (6) g/day protein achieving a total intake of 1142 (353) mg calcium/day and 69 (15) g/day protein (1.1 g/kg body weight). The 30 control facilities maintained their usual menus, with residents consuming 700 (247) mg/day calcium and 58 (14) g/day protein (0.9 g/kg body weight).Main outcome measuresGroup differences in incidence of fractures, falls, and all cause mortality.ResultsData from 27 intervention facilities and 29 control facilities were analysed. A total of 324 fractures (135 hip fractures), 4302 falls, and 1974 deaths were observed. The intervention was associated with risk reductions of 33% for all fractures (121v203; hazard ratio 0.67, 95% confidence interval 0.48 to 0.93; P=0.02), 46% for hip fractures (42v93; 0.54, 0.35 to 0.83; P=0.005), and 11% for falls (1879v<...
Jarman, LR, Elliott, JL, Lees, T, Clifton-Bligh, R, Simpson, AM, Nassif, N & Lal, S 2021, 'Heart Rate Variability as a Potential Non-invasive Marker of Blood Glucose Level', Human Physiology, vol. 47, no. 2, pp. 209-218.
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Abstract: Currently, monitoring of blood glucose level (BGL) is constrained by the invasive nature of BGL measures. We investigated heart rate variability (HRV) parameters as potential non-invasive markers of BGL. Healthy volunteers (n = 25; aged 27 ± 9 years) uninhibited by regular medications or chronic illness were recruited for this study. BGL and HRV were assessed during fasting (9:00 am), postprandial (12:00 pm), and postabsorptive (3:00 pm) periods using self-monitoring of blood glucose techniques and ten-minute electrocardiogram, respectively. Frequency-domain HRV measures, which estimate contributions of sympathetic and parasympathetic systems to autonomic modulation of the heart, were correlated against BGL data with the following significant (p < 0.05) findings. The change in BGL from fasting to postprandial levels was negatively correlated with fasting low frequency (LF) power and total power (TP). Postprandial BGL was negatively associated with fasting LF and TP, as well as with postprandial LF, high frequency (HF), and TP. The change in BGL from postprandial to postabsorptive levels was positively correlated with fasting LF power, as well as with postprandial LF, HF, and TP. Frequency-domain HRV parameters may be useful in predicting the magnitude and direction of acute fluctuations in BGL, and further research could develop them as non-invasive markers of BGL.
Jenner, S, Belski, R, Devlin, B, Coutts, A, Kempton, T & Forsyth, A 2021, 'A Qualitative Investigation of Factors Influencing the Dietary Intakes of Professional Australian Football Players', International Journal of Environmental Research and Public Health, vol. 18, no. 8, pp. 4205-4205.
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(1) Background: Many professional Australian Football (AF) players do not meet recommended sports nutrition guidelines despite having access to nutrition advice. There are a range of factors that can influence players′ ability to meet their nutrition goals and awareness of the barriers players face is essential to ensure that dietary advice translates into practice. Therefore, this qualitative research study aimed to explore the factors influencing AF players’ dietary intakes and food choice. (2) Methods: Semi-structured interviews were conducted with twelve professional male AF players. (3) Results: Less experienced players restricted their carbohydrate intake to meet body composition goals, particularly during preseason and surrounding body composition assessment. During the competition season players had a greater focus on performance and placed more emphasis on carbohydrate intake in the lead up to matches. Players felt nutrition goals were easier to achieve when dietary choices were supported by their families and peers. One-on-one consultations provided by a sports dietitian were players′ preferred mode of nutrition intervention. Individualized nutrition advice is required for less experienced AF players who may be vulnerable to unsustainable dietary habits. Experienced AF players can support junior teammates by promoting positive team culture related to body composition, nutrition and performance.
Jia, M, Gabrys, B & Musial, K 2021, 'Directed closure coefficient and its patterns', PLOS ONE, vol. 16, no. 6, pp. e0253822-e0253822.
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The triangle structure, being a fundamental and significant element, underlies many theories and techniques in studying complex networks. The formation of triangles is typically measured by the clustering coefficient, in which the focal node is the centre-node in an open triad. In contrast, the recently proposed closure coefficient measures triangle formation from an end-node perspective and has been proven to be a useful feature in network analysis. Here, we extend it by proposing the directed closure coefficient that measures the formation of directed triangles. By distinguishing the direction of the closing edge in building triangles, we further introduce the source closure coefficient and the target closure coefficient. Then, by categorising particular types of directed triangles (e.g., head-of-path), we propose four closure patterns. Through multiple experiments on 24 directed networks from six domains, we demonstrate that at network-level, the four closure patterns are distinctive features in classifying network types, while at node-level, adding the source and target closure coefficients leads to significant improvement in link prediction task in most types of directed networks.
Johnson, N, Maguire, S, Morra, A, Kapoor, PM, Tomczyk, K, Jones, ME, Schoemaker, MJ, Gilham, C, Bolla, MK, Wang, Q, Dennis, J, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Augustinsson, A, Baynes, C, Freeman, LEB, Beckmann, MW, Benitez, J, Bermisheva, M, Blomqvist, C, Boeckx, B, Bogdanova, NV, Bojesen, SE, Brauch, H, Brenner, H, Burwinkel, B, Campa, D, Canzian, F, Castelao, JE, Chanock, SJ, Chenevix-Trench, G, Clarke, CL, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Dörk, T, Eliassen, AH, Engel, C, Evans, DG, Fasching, PA, Figueroa, J, Floris, G, Flyger, H, Gago-Dominguez, M, Gapstur, SM, García-Closas, M, Gaudet, MM, Giles, GG, Goldberg, MS, González-Neira, A, Guénel, P, Hahnen, E, Haiman, CA, Håkansson, N, Hall, P, Hamann, U, Harrington, PA, Hart, SN, Hooning, MJ, Hopper, JL, Howell, A, Hunter, DJ, Jager, A, Jakubowska, A, John, EM, Kaaks, R, Keeman, R, Khusnutdinova, E, Kitahara, CM, Kosma, V-M, Koutros, S, Kraft, P, Kristensen, VN, Kurian, AW, Lambrechts, D, Le Marchand, L, Linet, M, Lubiński, J, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Mavroudis, D, Mayes, R, Meindl, A, Milne, RL, Neuhausen, SL, Nevanlinna, H, Newman, WG, Nielsen, SF, Nordestgaard, BG, Obi, N, Olshan, AF, Olson, JE, Olsson, H, Orban, E, Park-Simon, T-W, Peterlongo, P, Plaseska-Karanfilska, D, Pylkäs, K, Rennert, G, Rennert, HS, Ruddy, KJ, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmutzler, RK, Scott, C, Shu, X-O, Simard, J, Smichkoska, S, Sohn, C, Southey, MC, Spinelli, JJ, Stone, J, Tamimi, RM, Taylor, JA, Tollenaar, RAEM, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, van Veen, EM, Wang, SS, Weinberg, CR, Wendt, C, Wildiers, H, Winqvist, R, Wolk, A, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, PDP, Easton, DF, Howie, AF, Peto, J, dos-Santos-Silva, I, Swerdlow, AJ, Chang-Claude, J, Schmidt, MK, Orr, N & Fletcher, O 2021, 'CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers', British Journal of Cancer, vol. 124, no. 4, pp. 842-854.
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Abstract Background Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (−49.2%, 95% CI −56.1% to −41.1%, P = 3.1 × 10–18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (−26.7%, 95% CI −39.4% to −11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82–0.91, P = 6.9 × 10–8). Conclusions The CYP3A7*1C allele is associated with reduced risk of hormone recept...
Kalkhoven, JT, Watsford, ML, Coutts, AJ, Edwards, WB & Impellizzeri, FM 2021, 'Reply to “Comment on: Training Load and Injury: Causal Pathways and Future Directions”', Sports Medicine, vol. 51, no. 11, pp. 2451-2452.
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Kalkhoven, JT, Watsford, ML, Coutts, AJ, Edwards, WB & Impellizzeri, FM 2021, 'Training Load and Injury: Causal Pathways and Future Directions', Sports Medicine, vol. 51, no. 6, pp. 1137-1150.
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Causal pathways between training loads and the mechanisms of tissue damage and athletic injury are poorly understood. Here, the relation between specific training load measures and metrics, and causal pathways of gradual onset and traumatic injury are examined. Currently, a wide variety of internal and external training load measures and metrics exist, with many of these being commonly utilized to evaluate injury risk. These measures and metrics can conceptually be related to athletic injury through the mechanical load-response pathway, the psycho-physiological load-response pathway, or both. However, the contributions of these pathways to injury vary. Importantly, tissue fatigue damage and trauma through the mechanical load-response pathway is poorly understood. Furthermore, considerable challenges in quantifying this pathway exist within applied settings, evidenced by a notable absence of validation between current training load measures and tissue-level mechanical loads. Within this context, the accurate quantification of mechanical loads holds considerable importance for the estimation of tissue damage and the development of more thorough understandings of injury risk. Despite internal load measures of psycho-physiological load speculatively being conceptually linked to athletic injury through training intensity and the effects of psycho-physiological fatigue, these measures are likely too far removed from injury causation to provide meaningful, reliable relationships with injury. Finally, we used a common training load metric as a case study to show how the absence of a sound conceptual rationale and spurious links to causal mechanisms can disclose the weaknesses of candidate measures as tools for altering the likelihood of injuries, aiding the future development of more refined injury risk assessment methods.
Kang, H, Walsh, S, Oliver, B, Royce, T & Cho, BJ 2021, 'Exploring Heart Rate Variability as a Biomedical Diagnostic Tool for the Disympathetic Dimension of Eight-Constitution Medicine', Evidence-Based Complementary and Alternative Medicine, vol. 2021, pp. 1-13.
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Background. Eight-Constitution Medicine (ECM), an extension of Traditional Korean Medicine, divides the population into eight groups based on their physiological characteristics. ECM divides these eight groups into two larger groups based on autonomic reactivity: the Sympathicotonic group and the Vagotonic group (herein referred to as the Disympathetic Dimension). Heart Rate Variability (HRV) is a widely used biomedical tool to assess cardiac autonomic function. This raises the question of the utility of using HRV to correctly diagnose ECM constitutions. Methods. A systematic literature review was conducted to evaluate the correlation between HRV and constitutions in Korean Constitutional Medicine, including Eight-Constitution Medicine (ECM) and Sasang Constitution Medicine (SCM). The articles were obtained from both English (Scopus, PubMed, EMBASE, ProQuest, and Medline) and Korean databases (NDSL and RISS), in addition to Google Scholar, without date restriction. 20 studies met the inclusion criteria, and data were extracted against three aspects: (1) correlation between HRV and constitution, (2) HRV reporting and interpretation, and (3) extraneous factors that were controlled in the studies. Results. 386 articles were initially identified, which was reduced to n = 20 studies which met the inclusion criteria. Of these, 19 were SCM studies and 1 was an ECM study. Sample sizes varied from 10 to 8498 men and women, with an age range of 10–80 years. SCM studies explored HRV differences by constitution, measuring HRV at resting, with controlled breathing, before and after acupuncture stimulation, and by other interventions. SCM studies reported either no significant differences (HRV at resting or with controlled breathing studies) or conflicting data (HRV with acupuncture stimulation studies). The single ECM study measured HRV at resting and after acupuncture stimulation but reported no significant differences between the two groups of Sympathicoto...
Karacan, I, Cox, N, Dowd, A, Vago, R, Milthorpe, B, Cazalbou, S & Ben-Nissan, B 2021, 'The synthesis of hydroxyapatite from artificially grown Red Sea hydrozoan coral for antimicrobacterial drug delivery system applications', Journal of the Australian Ceramic Society, vol. 57, no. 2, pp. 399-407.
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The hydrozoan Millepora dichotoma (MD) is a typical Red Sea species containing a porous skeleton in the form of aragonite crystalline calcium carbonate. Due to environmental considerations, the artificial production of coralline species under controlled conditions is pertinent and underway. Artificially grown MD was used as a raw material for the production of calcium phosphate, mainly hydroxyapatite bioceramics, to be used in the drug delivery systems as a drug carrier or in the tissue engineering such as bone graft. DTA-TGA, XRD, FT-IR, Raman, and SEM analysis were carried out to analyze both unconverted and converted artificial corals. Hydrothermally converted coral fine powders were loaded with gentamicin (Gm) antibiotic, and the drug-loaded particles were analyzed by SEM. Unconverted coral was mainly aragonite, while hydrothermally treated coral was completely converted to hydroxyapatite. Hydrothermally treated coral was showing agglomerated nodules up to 1-μm size consisting of nanocrystalline hydroxyapatite platelets in the size range of less than 100 nm. The general macropore size of the coral was found to be appropriate for osteoid growth, which is 100 to 600 μm range. These artificially grown corals can be easily produced and used for bone growth and repair and other biomedical applications.
Katz, H, Newton-John, TRO & Shires, A 2021, 'Sexual Difficulties in the Population with Musculoskeletal Chronic Pain: A Systematic Review', Pain Medicine, vol. 22, no. 9, pp. 1982-1992.
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Abstract Objective To review the current literature on the nature and prevalence of sexual difficulties in the population with chronic musculoskeletal pain, as well as to identify the biopsychosocial factors that maintain these difficulties. Design Systematic review. Methods Studies were found by using multiple electronic databases and examining reference lists. After application of inclusion and exclusion criteria, 10 studies were eligible for review. Data were extracted and characteristics were described for outcomes of interest (i.e., sexual dysfunction, pain condition, pain intensity, psychosocial factors, gender differences). Cochrane Risk of Bias was assessed for all included studies. Results Ten studies (2,941 participants) were included in the review. Musculoskeletal conditions included low back pain and fibromyalgia. All studies examining sexual functioning found evidence of sexual difficulty among patients with chronic pain. Three studies demonstrated that sexual dysfunction was significantly greater in patients than in healthy matched controls. Nine studies found that greater pain levels significantly correlated with greater sexual dysfunction. Eight studies noted an increased prevalence of sexual difficulties in those with comorbid psychological problems. Heterogeneity between studies was identified, particularly with regard to gender outcomes. The risk-of-bias assessment also highlighted limitations in approximately half of studies.
Kennedy, PJ, Catchpoole, DR, Tafavogh, S, Harvey, BL & Aloqaily, AA 2021, 'Feature prioritisation on big genomic data for analysing gene-gene interactions', International Journal of Bioinformatics Research and Applications, vol. 17, no. 2, pp. 158-158.
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Kenny, P, Street, DJ, Hall, J, Agar, M & Phillips, J 2021, 'Valuing End-of-Life Care for Older People with Advanced Cancer: Is Dying at Home Important?', The Patient - Patient-Centered Outcomes Research, vol. 14, no. 6, pp. 803-813.
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Background
Most health care systems are facing the challenge of providing health services to support the increasing numbers of older people with chronic life-limiting conditions at the end of life. Many policies focus primarily on increasing the proportion of deaths at home.Objectives
This study aims to investigate preferences for care throughout the latter stages of a life-limiting illness, particularly the importance of location of care, location of death, and the use of life-sustaining measures. It focuses on preferences for the care of an older person with advanced cancer in the last 3 weeks of life.Methods
A survey using discrete choice experiment (DCE) methods was completed online by a general population sample of 1548 Australians aged 45 years and over. The experiment included 12 attributes, and each respondent completed 11 choice sets. Analysis was by a mixed logit model and latent class analysis (LCA).Results
The most important attributes influencing care preferences were cost, patient anxiety, pain control, and carer stress (relative importance scores 0.21, 0.19, 0.14, and 0.14, respectively), with less importance given to place of care and place of death (relative importance scores 0.03 and 0.01). The model predicted that 42% would consider receiving most care in hospital better than at home (58%) holding the levels of other attributes constant across the alternatives, while 42% would consider death in hospital better than at home (58%). Three population segments with different preferences were identified by the LCA, the largest (46.5%) prioritised how the patient and carer felt as well as the pain control achieved, the next largest (28.1%) prioritised cost, and the smallest segment (25.4%) prioritised a single room when an inpatient.Conclusions
This study shows that investment in services to support people at the end of life would be better targeted toward programmes that improve patient and carer well...
Khan, TA & Ling, SH 2021, 'A novel hybrid gravitational search particle swarm optimization algorithm', Engineering Applications of Artificial Intelligence, vol. 102, pp. 104263-104263.
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Khuat, TT & Gabrys, B 2021, 'An in-depth comparison of methods handling mixed-attribute data for general fuzzy min–max neural network', Neurocomputing, vol. 464, pp. 175-202.
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A general fuzzy min–max (GFMM) neural network is one of the efficient neuro-fuzzy systems for classification problems. However, a disadvantage of most of the current learning algorithms for GFMM is that they can handle effectively numerical valued features only. Therefore, this paper provides some potential approaches to adapting GFMM learning algorithms for classification problems with mixed-type or only categorical features as they are very common in practical applications and often carry very useful information. We will compare and assess three main methods of handling datasets with mixed features, including the use of encoding methods, the combination of the GFMM model with other classifiers, and employing the specific learning algorithms for both types of features. The experimental results showed that the target and James–Stein are appropriate categorical encoding methods for learning algorithms of GFMM models, while the combination of GFMM neural networks and decision trees is a flexible way to enhance the classification performance of GFMM models on datasets with the mixed features. The learning algorithms with the mixed-type feature abilities are potential approaches to deal with mixed-attribute data in a natural way, but they need further improvement to achieve a better classification accuracy. Based on the analysis, we also identify the strong and weak points of different methods and propose potential research directions.
Kim, RY, Oliver, BG, Wark, PAB, Hansbro, PM & Donovan, C 2021, 'COPD exacerbations: targeting IL-33 as a new therapy', The Lancet Respiratory Medicine, vol. 9, no. 11, pp. 1213-1214.
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Kochovska, S, Agar, MR, Phillips, JL, Tieman, J, Sheehan, C, Clark, K & Currow, DC 2021, 'Applying evidence-based symptomatic treatments from other clinical disciplines to palliative care', Palliative Medicine, vol. 35, no. 3, pp. 458-460.
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Kochovska, S, Ferreira, DH, Garcia, MV, Phillips, JL & Currow, DC 2021, 'Perspectives on palliative oxygen for breathlessness: systematic review and meta-synthesis', European Respiratory Journal, vol. 58, no. 4, pp. 2004613-2004613.
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Oxygen therapy is frequently prescribed for the palliation of breathlessness, despite lack of evidence for its effectiveness in people who are not hypoxaemic. This study aimed to compare and contrast patients’, caregivers’ and clinicians’ experiences of palliative oxygen use for the relief of chronic breathlessness in people with advanced life-limiting illnesses, and how this shapes prescribing.A systematic review and meta-synthesis of qualitative data was conducted. MEDLINE, CINAHL and PsycINFO were searched for peer-reviewed studies in English (2000–April 2019) reporting perspectives on palliative oxygen use for reducing breathlessness in people with advanced illnesses in any healthcare setting. After data extraction, thematic synthesis used line-by-line coding of raw data (quotes) to generate descriptive and analytical themes.Of 457 articles identified, 22 met the inclusion criteria by reporting perspectives of patients (n=337), caregivers (n=91) or clinicians (n=616). Themes common to these perspectives were: 1) benefits and burdens of palliative oxygen use, 2) knowledge and perceptions of palliative oxygen use beyond the guidelines, and 3) longitudinal trajectories of palliative oxygen use.There are differing perceptions regarding the benefits and burdens of using palliative oxygen. Clinicians should be aware that oxygen use may generate differing goals of therapy for patients and caregivers. These perceptions should be taken into consideration when prescribing oxygen for the symptomatic relief of chronic breathlessness in patients who do not quality for long-term oxygen therapy.
Kong, B, Sim, H-W, Amanuel, B, Day, B, Buckland, M, Verhaak, R, Yip, S, Johns, T, Lwin, Z, Rosenthal, M, Nowak, AK, Barnes, EH, Scott, AM, Parkinson, J, Jeffree, R, Lourenco, RDA, Lau, P, Whittle, J, Hovey, E, Cher, L, Kichendasse, G, Hall, M, Robinson, C, Thomas, M, Giardina, T, Tu, E, Khasraw, M, Koh, E-S & Gan, H 2021, 'INNV-08. LOW AND INTERMEDIATE GRADE GLIOMA UMBRELLA STUDY OF MOLECULAR GUIDED THERAPIES (LUMOS) STUDY', Neuro-Oncology, vol. 23, no. Supplement_6, pp. vi106-vi107.
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Abstract BACKGROUND Grade 2 and 3 (G2/3) gliomas are the second largest group of brain tumors in adults. Although the prognosis for G2/3 gliomas at the time of relapse mirror those of glioblastoma, there are few trials in this space. METHODS LUMOS was a national multi-center pilot study for patients with relapsed G2/3 gliomas designed to match contemporaneous tissue obtained at the time of disease progression with subsequent targeted therapies. The objective was to establish the feasibility of a precision oncology, umbrella approach to obtain and type tissue within a useful timeframe. As a key feature of LUMOS, a multidisciplinary Molecular Tumor Advisory Panel (MTAP) with subspecialty neuro-oncology expertise was formed to interpret the complex genomic information and provide a simplified recommendation to the treating physician. RESULTS Ten patients (median age 42: range 32-62; four G2 astrocytoma, one G3 astrocytoma, three G2 oligoendroglioma, one G3 oligodendroglioma, one mixed tumor) were enrolled in the study. Eight patients had biopsies within 6 months of study entry whilst two underwent a biopsy during the study. All patients had potentially targetable alterations (10 IDH, 3 FGFR, 2 PIK3K, CCND3, NRAS, CDK4, PRPRZ1-MET fusion and MET amplification). Matched therapies were delivered for two patients via compassionate access outside the study. The median turnaround time (TAT) of MTAP reports was 6.2 weeks (range 4.2-9.7 weeks) but 4.6 weeks when lag time for shipping was removed. CO...
Kong, BY, Sim, H-W, Nowak, AK, Yip, S, Barnes, EH, Day, BW, Buckland, ME, Verhaak, R, Johns, T, Robinson, C, Thomas, MA, Giardina, T, Lwin, Z, Scott, AM, Parkinson, J, Jeffree, R, Lourenco, RDA, Hovey, EJ, Cher, LM, Kichendasse, G, Khasraw, M, Hall, M, Tu, E, Amanuel, B, Koh, E-S & Gan, HK 2021, 'LUMOS - Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS at relapse: Protocol for a pilot study', BMJ Open, vol. 11, no. 12, pp. e054075-e054075.
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IntroductionGrades 2 and 3 gliomas (G2/3 gliomas), when combined, are the second largest group of malignant brain tumours in adults. The outcomes for G2/3 gliomas at progression approach the dismal outcomes for glioblastoma (GBM), yet there is a paucity of trials for Australian patients with relapsed G2/3 gliomas compared with patients with GBM. LUMOS will be a pilot umbrella study for patients with relapsed G2/3 gliomas that aims to match patients to targeted therapies based on molecular screening with contemporaneous tumour tissue. Participants in whom no actionable or no druggable mutation is found, or in whom the matching drug is not available, will form a comparator arm and receive standard of care chemotherapy. The objective of the LUMOS trial is to assess the feasibility of this approach in a multicentre study across five sites in Australia, with a view to establishing a national molecular screening platform for patient treatment guided by the mutational analysis of contemporaneous tissue biopsiesMethods and analysisThis study will be a multicentre pilot study enrolling patients with recurrent grade 2/3 gliomas that have previously been treated with radiotherapy and chemotherapy at diagnosis or at first relapse. Contemporaneous tumour tissue at the time of first relapse, defined as tissue obtained within 6 months of relapse and without subsequent intervening therapy, will be obtained from patients. Molecular screening will be performed by targeted next-generation sequencing at the reference laboratory (PathWest, Perth, Australia). RNA and DNA will be extracted from representative formalin-fixed paraffin embedded tissue scrolls or microdissected from sections on glass slides tissue sections following a review of the histology by pathologists. Extracted nucleic acid will be quantified by Qubit Fluorometric Quantitation (Thermo Fisher Scientific...
Kong, BY, Sim, H-W, Nowak, AK, Yip, S, Barnes, EH, Day, BW, Buckland, ME, Verhaak, R, Johns, T, Robinson, C, Thomas, MA, Giardina, T, Lwin, Z, Scott, AM, Parkinson, J, Jeffree, R, Lourenco, RDA, Hovey, EJ, Cher, LM, Kichendasse, G, Khasraw, M, Hall, M, Tu, E, Amanuel, B, Koh, E-S & Gan, HK 2021, 'LUMOS - Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS at relapse: Protocol for a pilot study.', BMJ open, vol. 11, no. 12, p. e054075.
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Introduction
Grades 2 and 3 gliomas (G2/3 gliomas), when combined, are the second largest group of malignant brain tumours in adults. The outcomes for G2/3 gliomas at progression approach the dismal outcomes for glioblastoma (GBM), yet there is a paucity of trials for Australian patients with relapsed G2/3 gliomas compared with patients with GBM. LUMOS will be a pilot umbrella study for patients with relapsed G2/3 gliomas that aims to match patients to targeted therapies based on molecular screening with contemporaneous tumour tissue. Participants in whom no actionable or no druggable mutation is found, or in whom the matching drug is not available, will form a comparator arm and receive standard of care chemotherapy. The objective of the LUMOS trial is to assess the feasibility of this approach in a multicentre study across five sites in Australia, with a view to establishing a national molecular screening platform for patient treatment guided by the mutational analysis of contemporaneous tissue biopsies METHODS AND ANALYSIS: This study will be a multicentre pilot study enrolling patients with recurrent grade 2/3 gliomas that have previously been treated with radiotherapy and chemotherapy at diagnosis or at first relapse. Contemporaneous tumour tissue at the time of first relapse, defined as tissue obtained within 6 months of relapse and without subsequent intervening therapy, will be obtained from patients. Molecular screening will be performed by targeted next-generation sequencing at the reference laboratory (PathWest, Perth, Australia). RNA and DNA will be extracted from representative formalin-fixed paraffin embedded tissue scrolls or microdissected from sections on glass slides tissue sections following a review of the histology by pathologists. Extracted nucleic acid will be quantified by Qubit Fluorometric Quantitation (Thermo Fisher Scientific). Library preparation and targeted capture will be performed using the TruSight Tumor 170 (TS...
Lan, T, Hutvagner, G, Lan, Q, Liu, T & Li, J 2021, 'Sequencing dropout-and-batch effect normalization for single-cell mRNA profiles: a survey and comparative analysis', Briefings in Bioinformatics, vol. 22, no. 4.
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AbstractSingle-cell mRNA sequencing has been adopted as a powerful technique for understanding gene expression profiles at the single-cell level. However, challenges remain due to factors such as the inefficiency of mRNA molecular capture, technical noises and separate sequencing of cells in different batches. Normalization methods have been developed to ensure a relatively accurate analysis. This work presents a survey on 10 tools specifically designed for single-cell mRNA sequencing data preprocessing steps, among which 6 tools are used for dropout normalization and 4 tools are for batch effect correction. In this survey, we outline the main methodology for each of these tools, and we also compare these tools to evaluate their normalization performance on datasets which are simulated under the constraints of dropout inefficiency, batch effect or their combined effects. We found that Saver and Baynorm performed better than other methods in dropout normalization, in most cases. Beer and Batchelor performed better in the batch effect normalization, and the Saver–Beer tool combination and the Baynorm–Beer combination performed better in the mixed dropout-and-batch effect normalization. Over-normalization is a common issue occurred to these dropout normalization tools that is worth of future investigation. For the batch normalization tools, the capability of retaining heterogeneity between different groups of cells after normalization can be another direction for future improvement.
Larkin, BP, Nguyen, LT, Hou, M, Glastras, SJ, Chen, H, Wang, R, Pollock, CA & Saad, S 2021, 'Novel Role of Gestational Hydralazine in Limiting Maternal and Dietary Obesity-Related Chronic Kidney Disease', Frontiers in Cell and Developmental Biology, vol. 9.
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BackgroundMaternal obesity is a risk factor for chronic kidney disease (CKD) in offspring, underpinning the theory of the developmental origins of health and disease. DNA methylation has been implicated in the programming of adult chronic disease by maternal obesity, therefore, DNA demethylating agents may mitigate offspring risk of disease. In rodent models, low-dose hydralazine has previously been shown to reduce renal fibrosis via DNA demethylation. We used mouse models of maternal obesity and offspring obesity to determine whether administration of low-dose hydralazine during gestation can prevent fetal programming of CKD in offspring.MethodsFemale C57BL/6 mice received high fat diet (HFD) or chow prior to mating, during gestation and lactation. During gestation, dams received subcutaneous hydralazine (5 mg/kg) or saline thrice-weekly. Male offspring weaned to HFD or chow, which continued until endpoint at 32 weeks. Biometric and metabolic parameters, renal global DNA methylation, renal functional and structural changes, and renal markers of fibrosis, inflammation and oxidative stress were assessed at endpoint.ResultsOffspring exposed to maternal obesity or diet-induced obesity had significantly increased renal global DNA methylation, together with other adverse renal effects including albuminuria, glomerulosclerosis, renal fibrosis, and oxidative stress. Offspring exposed to gestational hydralazine had significantly reduced renal global DNA methylation. In obese offspring of obese mothers, gestational hydralazine significantly decreased albuminuria, glomerulosclerosis, and serum creatinine. Obese offspring of hydralazine-treated lean mothers displayed reduced markers of renal fibrosis and oxidative stress.ConclusionGesta...
Larkin, BP, Saad, S, Glastras, SJ, Nguyen, LT, Hou, M, Chen, H, Wang, R & Pollock, CA 2021, 'Low-dose hydralazine during gestation reduces renal fibrosis in rodent offspring exposed to maternal high fat diet', PLOS ONE, vol. 16, no. 3, pp. e0248854-e0248854.
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BackgroundMaternal high fat diet (HFD) promotes chronic kidney disease (CKD) in offspring. This is in accordance with the theory of fetal programming, which suggests adverse conditions occurring in utero predispose offspring to chronic conditions later in life. DNA methylation has been proposed as a key mechanism by which fetal programming occurs and is implicated in CKD progression. DNA demethylating drugs may interrupt the fetal programming of CKD by maternal obesity. Hydralazine, an antihypertensive agent, demethylates DNA at low doses which do not reduce blood pressure. We used a mouse model of maternal obesity to determine whether gestational administration of low-dose hydralazine to mothers can prevent CKD in offspring.MethodsC57BL/6 dams received HFD or chow from 6 weeks prior to mating and were administered subcutaneous hydralazine (5mg/kg) or saline thrice weekly during gestation. Male offspring were weaned to chow and were sacrificed at either postnatal week 9 or week 32. Biometric and metabolic parameters, renal global DNA methylation, renal structural and functional changes and markers of fibrosis, oxidative stress and inflammation were measured in offspring at weeks 9 and 32.ResultsIn week 9 offspring, maternal HFD consumption did not significantly alter anthropometric or metabolic parameters, or renal global DNA methylation. Week 32 offspring had increased renal global DNA methylation, together with albuminuria, glomerulosclerosis, renal fibrosis and oxidative stress. Administration of low-dose hydralazine to obese mothers during gestation reduced renal global DNA methylation and renal fibrotic markers in week 32 offspring.Conclusion...
Lee, L-Y, Hew, GSY, Mehta, M, Shukla, SD, Satija, S, Khurana, N, Anand, K, Dureja, H, Singh, SK, Mishra, V, Singh, PK, Gulati, M, Prasher, P, Aljabali, AAA, Tambuwala, MM, Thangavelu, L, Panneerselvam, J, Gupta, G, Zacconi, FC, Shastri, M, Jha, NK, Xenaki, D, MacLoughlin, R, Oliver, BG, Chellappan, DK & Dua, K 2021, 'Targeting eosinophils in respiratory diseases: Biological axis, emerging therapeutics and treatment modalities', Life Sciences, vol. 267, pp. 118973-118973.
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Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders.
Lee, W, Pulbrook, M, Sheehan, C, Kochovska, S, Chang, S, Hosie, A, Lobb, E, Parker, D, Draper, B, Agar, MR & Currow, DC 2021, 'Clinically Significant Depressive Symptoms Are Prevalent in People With Extremely Short Prognoses—A Systematic Review', Journal of Pain and Symptom Management, vol. 61, no. 1, pp. 143-166.e2.
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Context
Currently, systematic evidence of the prevalence of clinically significant depressive symptoms in people with extremely short prognoses is not available to inform its global burden, assessment, and management.
Objectives
To determine the prevalence of clinically significant depressive symptoms in people with advanced life-limiting illnesses and extremely short prognoses (range of days to weeks).
Methods
A systematic review and meta-analysis (random-effects model) were performed (PROSPERO: CRD42019125119). MEDLINE, Embase, PsycINFO, CINAHL, and CareSearch were searched for studies (1994-2019). Data were screened for the prevalence of clinically significant depressive symptoms (assessed using validated depression-specific screening tools or diagnostic criteria) of adults with advanced life-limiting illnesses and extremely short prognoses (defined by survival or functional status). Quality assessment was performed using the Joanna Briggs Institute Systematic Reviews Checklist for Prevalence Studies for individual studies and Grading of Recommendations Assessment, Development and Evaluation (GRADE) across studies.
Results
Thirteen studies were included. The overall pooled prevalence of clinically significant depressive symptoms in adults with extremely short prognoses (n = 10 studies; extremely short prognoses: N = 905) using depression-specific screening tools was 50% (95% CI: 29%-70%; I
2 = 97.6%). Prevalence of major and minor depression was 10% (95% CI: 4%-16%) and 5% (95% CI: 2%-8%), respectively. Major limitations included high heterogeneity, selection bias, and small sample sizes in individual studies.
Conclusions
Clinically, significant depressive symptoms were prevalent in people with advanced life-limiting illnesses and extremely short prognoses. Clinicians need to be proactive in the recognition and assessment of these symptoms to allow for timely intervention.
Lees, T, Chalmers, T, Burton, D, Zilberg, E, Penzel, T, Lal, S & Lal, S 2021, 'Electrophysiological Brain-Cardiac Coupling in Train Drivers during Monotonous Driving', International Journal of Environmental Research and Public Health, vol. 18, no. 7, pp. 3741-3741.
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Electrophysiological research has previously investigated monotony and the cardiac health of drivers independently; however, few studies have explored the association between the two. As such the present study aimed to examine the impact of monotonous train driving (indicated by electroencephalogram (EEG) activity) on an individual’s cardiac health as measured by heart rate variability (HRV). Sixty-three train drivers participated in the present study, and were required to complete a monotonous train driver simulator task. During this task, a 32 lead EEG and a three-lead electrocardiogram were recorded from each participant. In the present analysis, the low (LF) and high frequency (HF) HRV parameters were associated with delta (p < 0.05), beta (p = 0.03) and gamma (p < 0.001) frequency EEG variables. Further, total HRV was associated with gamma activity, while sympathovagal balance (i.e., LF:HF ratio) was best associated fronto-temporal delta activity (p = 0.02). HRV and EEG parameters appear to be coupled, with the parameters of the delta and gamma EEG frequency bands potentially being the most important to this coupling. These relationships provide insight into the impact of a monotonous task on the cardiac health of train drivers, and may also be indicative of strategies employed to combat fatigue or engage with the driving task.
Lewandowska, M, De Abreu Lourenco, R, Haas, M, Watson, CJ, Black, KI, Taft, A, Lucke, J, McGeechan, K, McNamee, K, Peipert, JF & Mazza, D 2021, 'Cost-effectiveness of a complex intervention in general practice to increase uptake of long-acting reversible contraceptives in Australia', Australian Health Review, vol. 45, no. 6, pp. 728-734.
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Objective The aim of this study was to evaluate the cost-effectiveness of the Australian Contraceptive ChOice pRoject (ACCORd) intervention. Methods An economic evaluation compared the costs and outcomes of the ACCORd intervention with usual care (UC). Data from the ACCORd trial were used to estimate costs and efficacy in terms of contraceptive uptake and quality of life. Rates of contraceptive failure and pregnancy were sourced from the literature. Using a Markov model, within-trial results were extrapolated over 10 years and subjected to univariate sensitivity analyses. Model outputs were expressed as the cost per quality-adjusted life years (QALY) gained and cost per unintended pregnancy resulting in birth (UPB) avoided. Results Over 10 years, compared with UC, initiating contraception through the ACCORd intervention resulted in 0.02 fewer UPB and higher total costs (A$2505 vs A$1179) per woman. The incremental cost-effectiveness of the ACCORd intervention versus UC was A$1172 per QALY gained and A$7385 per UPB averted. If the start-up cost of the ACCORd intervention was removed, the incremental cost-effectiveness ratio was A$81 per QALY gained and A$511 per UPB averted. The results were most sensitive to the probability of contraceptive failure, the probability of pregnancy-related healthcare service utilisation or the inclusion of the costs of implementing the ACCORd intervention. Conclusions From a health system perspective, if implemented appropriately in terms of uptake and reach, and assuming an implicit willingness to pay threshold of A$50 000 the ACCORd intervention is cost-effective. What is known about the topic? The uptake of long-active reversible contraceptives (LARC) in Australia is low. The ACCORd trial assessed the efficacy of providing structured training to general practitioners (GPs) on LARC counselling, together with access to rapid referral to insertion clinics. What does this paper add? This study is the ...
Li, H, Chen, H, Morgan, L, Li, W & Oliver, BG 2021, 'A narrative review of clinical studies of herbal treatment of difficult to manage asthma', Complementary Therapies in Clinical Practice, vol. 44, pp. 101433-101433.
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Asthma can be complex and difficult to manage. Patients often seek alternative treatment options, including Traditional Chinese Medicine (TCM). The paradigms that inform TCM treatments include a philosophy focusing on modifying the whole body status ('bian zheng') to treat the lungs. TCM practitioners use personalized treatment plans based on clusters of clinical patterns (eg. cold-related wheezing, kidney insufficiency/energy-deficiency-related wheezing). TCM includes herbal remedies and non-oral therapies such as cupping, acupuncture, and massage. The efficacy of TCM treatments of asthma is not well described as the majority of studies are published only in Chinese literature. We reviewed all available clinical trials in CNKI, Chaoxin, Wanfang, CQVIP, Springer-link, Science Direct, and Pubmed. Papers in Chinese were translated by dual lingual TCM and Western medicine doctors. Based on the identified studies, TCM is a safe additive treatment to Western medicine that can improve both symptoms and quality of life for patients with asthma.
Li, J, Xie, Y, Zhao, P, Qin, Y, Oliver, BG, Tian, Y, Li, S, Wang, M & Liu, X 2021, 'A chinese herbal formula ameliorates COPD by inhibiting the inflammatory response via downregulation of p65, JNK, and p38', Phytomedicine, vol. 83, pp. 153475-153475.
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BackgroundBufei Yishen formula (BYF), a traditional Chinese medicine (TCM), is an effective therapeutic strategy for patients with chronic obstructive pulmonary disease (COPD).PurposeTo evaluate the efficacy of BYF and investigate its therapeutic mechanisms.MethodsA total of 134 patients completed the study: 68 patients treated by BYF combined with conventional Western medicine in the trial group; and 66 patients treated using conventional Western medicine in the control group. The efficacy of BYF was evaluated by a subgroup analysis of data obtained from a four-center, open-label, randomized controlled trial of comprehensive TCM interventions. A rat model of COPD was treated with the key active molecules (KAM) of BYF for 8 weeks. An in vitro model of COPD was also treated with KAM.ResultsPatients treated with BYF had reduced frequency of acute exacerbation of COPD (p < 0.001) and duration (p = 0.028), dyspnea scale (p = 0.007), 6-min walking distance (p = 0.048). There were no differences observed in forced vital capacity in one second (FVC), forced expiratory volume in one second (FEV1), and FEV1 percentage of the predicted value (FEV1%). The five KAM of BYF (KAM-BYF) improved lung function, including tidal volume, minute ventilation, peak expiratory flow, FVC, FEV0.1, and FEV0.3, and pathological changes in COPD rats. Treatment with KAM-BYF markedly decreased the levels of interleukin 6 (IL6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase 9 (MMP9), and MMP12 in serum and bronchial alveolar lavage fluid. In airway epithelial cells, KAM-BYF decreased the levels of TNF-α-induced IL8 and IL6. Finally, we discovered that the anti-inflammatory effects of KAM-BYF in COPD rats and BEAS-2Bs were mediated through inhibition of nuclear factor-kappaB (NF-κB) p65, c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase signaling.ConclusionsBYF exerts beneficial effects in patients with COPD via inhibition of inflammation.
Li, X, Xiang, J, Wang, J, Li, J, Wu, F-X & Li, M 2021, 'FUNMarker: Fusion Network-Based Method to Identify Prognostic and Heterogeneous Breast Cancer Biomarkers', IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol. 18, no. 6, pp. 2483-2491.
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Breast cancer is a heterogeneous disease with many clinically distinguishable molecular subtypes each corresponding to a cluster of patients. Identification of prognostic and heterogeneous biomarkers for breast cancer is to detect cluster-specific gene biomarkers which can be used for accurate survival prediction of breast cancer outcomes. In this study, we proposed a FUsion Network-based method (FUNMarker) to identify prognostic and heterogeneous breast cancer biomarkers by considering the heterogeneity of patient samples and biological information from multiple sources. To reduce the affect of heterogeneity of patients, samples were first clustered using the K-means algorithm based on the principal components of gene expression. For each cluster, to comprehensively evaluate the influence of genes on breast cancer, genes were weighted from three aspects: biological function, prognostic ability and correlation with known disease genes. Then they were ranked via a label propagation model on a fusion network that combined physical protein interactions from seven types of networks and thus could reduce the impact of incompleteness of interactome. We compared FUNMarker with three state-of-the-art methods and the results showed that biomarkers identified by FUNMarker were biological interpretable and had stronger discriminative power than the existing methods in differentiating patients with different prognostic outcomes.
Liu Chung Ming, C, Sesperez, K, Ben-Sefer, E, Arpon, D, McGrath, K, McClements, L & Gentile, C 2021, 'Considerations to Model Heart Disease in Women with Preeclampsia and Cardiovascular Disease', Cells, vol. 10, no. 4, pp. 899-899.
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Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation, and is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to the variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD), including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion; however, this therapeutic approach leads to ischemic/reperfusion injury (IRI), often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.
Liu, Y & Li, J 2021, 'Hamming-shifting graph of genomic short reads: Efficient construction and its application for compression', PLOS Computational Biology, vol. 17, no. 7, pp. e1009229-e1009229.
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Graphs such as de Bruijn graphs and OLC (overlap-layout-consensus) graphs have been widely adopted for the de novo assembly of genomic short reads. This work studies another important problem in the field: how graphs can be used for high-performance compression of the large-scale sequencing data. We present a novel graph definition named Hamming-Shifting graph to address this problem. The definition originates from the technological characteristics of next-generation sequencing machines, aiming to link all pairs of distinct reads that have a small Hamming distance or a small shifting offset or both. We compute multiple lexicographically minimal k-mers to index the reads for an efficient search of the weight-lightest edges, and we prove a very high probability of successfully detecting these edges. The resulted graph creates a full mutual reference of the reads to cascade a code-minimized transfer of every child-read for an optimal compression. We conducted compression experiments on the minimum spanning forest of this extremely sparse graph, and achieved a 10 − 30% more file size reduction compared to the best compression results using existing algorithms. As future work, the separation and connectivity degrees of these giant graphs can be used as economical measurements or protocols for quick quality assessment of wet-lab machines, for sufficiency control of genomic library preparation, and for accurate de novo genome assembly.
Liu, Y, Zhang, L, Li, HL, Liang, BM, Wang, J, Zhang, X, Chen, ZH, Zhang, HP, Xie, M, Wang, L, Wang, G & Oliver, BG 2021, 'Small Airway Dysfunction in Asthma Is Associated with Perceived Respiratory Symptoms, Non-Type 2 Airway Inflammation, and Poor Responses to Therapy', Respiration, vol. 100, no. 8, pp. 767-779.
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<b><i>Background:</i></b> Emerging evidence has indicated that small airway dysfunction (SAD) contributes to the clinical expression of asthma. <b><i>Objectives:</i></b> The aim of the study was to explore the relationships of SAD assessed by forced expiratory flow between 25 and 75% (FEF<sub>25–75</sub>%), with clinical and inflammatory profile and treatment responsiveness in asthma. <b><i>Method:</i></b> In study I, dyspnea intensity (Borg scale), chest tightness, wheezing and cough (visual analog scales, VASs), and pre- and post-methacholine challenge testing (MCT) were analyzed in asthma patients with SAD and non-SAD. In study II, asthma subjects with SAD and non-SAD underwent sputum induction, and inflammatory mediators in sputum were detected. Asthma patients with SAD and non-SAD receiving fixed treatments were prospectively followed up for 4 weeks in study III. Spirometry, Asthma Control Questionnaire (ACQ), and Asthma Control Test (ACT) were carried out to define treatment responsiveness. <b><i>Results:</i></b> SAD subjects had more elevated ΔVAS for dyspnea (<i>p</i> = 0.027) and chest tightness (<i>p</i> = 0.032) after MCT. Asthma patients with SAD had significantly elevated interferon (IFN)-γ in sputum (<i>p</i> < 0.05), and Spearman partial correlation found FEF<sub>25–75</sub>% significantly related to IFN-γ and interleukin-8 (both having <i>p</i> < 0.05). Furthermore, multivariable regression analysis indicated SAD was significantly associated with worse treatment responses (decrease in ACQ ≥0.5 and increase in ACT ≥3) (<i>p</i> = 0.022 and <i>p</i> = 0.032). <b><i>Conclusions:</i></b> This study indicates that SAD in asthma predisposes patients to greater dyspnea intensity and chest tightness during b...
Liu, Y, Zhou, Z, Wang, F, Kewes, G, Wen, S, Burger, S, Ebrahimi Wakiani, M, Xi, P, Yang, J, Yang, X, Benson, O & Jin, D 2021, 'Axial localization and tracking of self-interference nanoparticles by lateral point spread functions', Nature Communications, vol. 12, no. 1, pp. 1-9.
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AbstractSub-diffraction limited localization of fluorescent emitters is a key goal of microscopy imaging. Here, we report that single upconversion nanoparticles, containing multiple emission centres with random orientations, can generate a series of unique, bright and position-sensitive patterns in the spatial domain when placed on top of a mirror. Supported by our numerical simulation, we attribute this effect to the sum of each single emitter’s interference with its own mirror image. As a result, this configuration generates a series of sophisticated far-field point spread functions (PSFs), e.g. in Gaussian, doughnut and archery target shapes, strongly dependent on the phase difference between the emitter and its image. In this way, the axial locations of nanoparticles are transferred into far-field patterns. We demonstrate a real-time distance sensing technology with a localization accuracy of 2.8 nm, according to the atomic force microscope (AFM) characterization values, smaller than 1/350 of the excitation wavelength.
Logan, J, Kennedy, PJ & Catchpoole, D 2021, 'The Untapped Social Impact of Artificial Intelligence for Breast Cancer Screening in Developing Countries: A Critical Commentary of DeepMind', Innovations in Digital Health, Diagnostics, and Biomarkers, vol. 1, no. 2, pp. 29-32.
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Luckett, T, Donkor, A, Phillips, J, Currow, DC, Parker, D, Lobb, E & Agar, MR 2021, 'Australian specialist palliative care’s response to COVID-19: an anonymous online survey of service providers', Annals of Palliative Medicine, vol. 10, no. 3, pp. 2747-2757.
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Background
The corona virus disease 2019 (COVID-19) pandemic has required specialist palliative care (SPC) services to respond by: (I) integrating infection prevention/control measures into care for their usual caseloads and (II) providing consultations and/or care for people dying from a new disease entity. The aim of the current study was to learn about the response of Australian SPC services to COVID-19 and its consequences in order to inform pandemic practice and policy.
Methods
A cross-sectional, anonymous survey was administered online from May to July 2020. Email invitations were sent to 160 providers delivering 503 SPC services listed in the Australian Palliative Care Services Directory. Survey questions asked about service responses to COVID-19, impacts on care quality, and perceived benefits/disadvantages for palliative care clients post-pandemic. Open-ended responses were thematically coded using an established framework that classifies SPC pandemic responses under: 'stuff', 'staff', 'space', 'systems', 'separation', 'sedation', 'communication' and 'equity'.
Results
Complete survey responses were received from 28 providers on behalf of 100 SPC services (response rates of 17%/20% respectively): 29 consultative, 25 community home-based, 21 outpatient, 15 inpatient wards/units, eight inpatient hospice and two other services. Responses were reported across all framework categories except 'sedation'. Concerns centred on: inadequate support for self-management, psychosocial needs and bereavement for clients living at home; pressures on staff capacity and wellbeing; and a perceived lack of health system preparedness for a potential future surge. Rapid implementation of telehealth across Australia was perceived to offer potential benefits to palliative care in the longer term, if provided with ongoing support.
Conclusions
Meeting COVID-19-related challenges requires SPC to be agile and responsive. Advocacy is required to ...
Luckett, T, Luscombe, G, Phillips, J, Beattie, E, Chenoweth, L, Davidson, PM, Goodall, S, Pond, D, Mitchell, G & Agar, M 2021, 'Australian long-term care personnel’s knowledge and attitudes regarding palliative care for people with advanced dementia', Dementia, vol. 20, no. 2, pp. 427-443.
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This study aimed to describe Australian long-term care (LTC) personnel’s knowledge and attitudes concerning palliative care for residents with advanced dementia, and explore relationships with LTC facility/personnel characteristics. An analysis was undertaken of baseline data from a cluster randomised controlled trial of facilitated family case conferencing for improving palliative care of LTC residents with advanced dementia (the ‘IDEAL Study’). Participants included any LTC personnel directly involved in residents’ care. Knowledge and attitudes concerning palliative care for people with advanced dementia were measured using the questionnaire on Palliative Care for Advanced Dementia. Univariate and multivariate analyses explored relationships between personnel knowledge/attitudes and facility/personnel characteristics. Of 307 personnel in the IDEAL Study, 290 (94.5%) from 19/20 LTCFs provided sufficient data for inclusion. Participants included 9 (2.8%) nurse managers, 59 (20.5%) registered nurses, 25 (8.7%) enrolled nurses, 187 (64.9%) assistants in nursing/personal care assistants and 9 (3.1%) care service employees. In multivariate analyses, a facility policy not to rotate personnel through dementia units was the only variable associated with more favourable overall personnel knowledge and attitudes. Other variables associated with favourable knowledge were a designation of nursing manager or registered or enrolled nurse, and having a preferred language of English. Other variables associated with favourable attitudes were tertiary level of education and greater experience in dementia care. Like previous international research, this study found Australian LTC personnel knowledge and attitudes regarding palliative care for people with advanced dementia to be associated with both facility and personnel characteristics. Future longitudinal research is needed to better understand the relationships between knowledge and attitudes, as well as betw...
Lyu, J, Bi, X, Banerjee, S, Huang, Z, Leung, FHF, Lee, TT-Y, Yang, D-D, Zheng, Y-P & Ling, SH 2021, 'Dual-task ultrasound spine transverse vertebrae segmentation network with contour regularization', Computerized Medical Imaging and Graphics, vol. 89, pp. 101896-101896.
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3D ultrasound imaging has become one of the common diagnosis ways to assess scoliosis since it is radiation-free, real-time, and low-cost. Spine curvature angle measurement is an important step to assess scoliosis precisely. One way to calculate the angle is using the vertebrae features of the 2-D coronal images to identify the most tilted vertebrae. To do the measurement, the segmentation of the transverse vertebrae is an important step. In this paper, we propose a dual-task ultrasound transverse vertebrae segmentation network (D-TVNet) based on U-Net. First, we arrange an auxiliary shape regularization network to learn the contour segmentation of the bones. It improves the boundary segmentation and anti-interference ability of the U-Net by fusing some of the features of the auxiliary task and the main task. Then, we introduce the atrous spatial pyramid pooling (ASPP) module to the end of the down-sampling stage of the main task stream to improve the relative feature extraction ability. To further improve the boundary segmentation, we extendedly fuse the down-sampling output features of the auxiliary network in the ASPP. The experiment results show that the proposed D-TVNet achieves the best dice score of 86.68% and the mean dice score of 86.17% based on cross-validation, which is an improvement of 5.17% over the baseline U-Net. An automatic ultrasound spine bone segmentation network with promising results has been achieved.
Lyu, J, Ling, SH, Banerjee, S, Zheng, JY, Lai, KL, Yang, D, Zheng, YP, Bi, X, Su, S & Chamoli, U 2021, 'Ultrasound volume projection image quality selection by ranking from convolutional RankNet', Computerized Medical Imaging and Graphics, vol. 89, pp. 101847-101847.
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Periodic inspection and assessment are important for scoliosis patients. 3D ultrasound imaging has become an important means of scoliosis assessment as it is a real-time, cost-effective and radiation-free imaging technique. With the generation of a 3D ultrasound volume projection spine image using our Scolioscan system, a series of 2D coronal ultrasound images are produced at different depths with different qualities. Selecting a high quality image from these 2D images is the crucial task for further scoliosis measurement. However, adjacent images are similar and difficult to distinguish. To learn the nuances between these images, we propose selecting the best image automatically, based on their quality rankings. Here, the ranking algorithm we use is a pairwise learning-to-ranking network, RankNet. Then, to extract more efficient features of input images and to improve the discriminative ability of the model, we adopt the convolutional neural network as the backbone due to its high power of image exploration. Finally, by inputting the images in pairs into the proposed convolutional RankNet, we can select the best images from each case based on the output ranking orders. The experimental result shows that convolutional RankNet achieves better than 95.5% top-3 accuracy, and we prove that this performance is beyond the experience of a human expert.
Mac Aogáin, M, Narayana, JK, Tiew, PY, Ali, NABM, Yong, VFL, Jaggi, TK, Lim, AYH, Keir, HR, Dicker, AJ, Thng, KX, Tsang, A, Ivan, FX, Poh, ME, Oriano, M, Aliberti, S, Blasi, F, Low, TB, Ong, TH, Oliver, B, Giam, YH, Tee, A, Koh, MS, Abisheganaden, JA, Tsaneva-Atanasova, K, Chalmers, JD & Chotirmall, SH 2021, 'Integrative microbiomics in bronchiectasis exacerbations', Nature Medicine, vol. 27, no. 4, pp. 688-699.
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Bronchiectasis, a progressive chronic airway disease, is characterized by microbial colonization and infection. We present an approach to the multi-biome that integrates bacterial, viral and fungal communities in bronchiectasis through weighted similarity network fusion ( https://integrative-microbiomics.ntu.edu.sg ). Patients at greatest risk of exacerbation have less complex microbial co-occurrence networks, reduced diversity and a higher degree of antagonistic interactions in their airway microbiome. Furthermore, longitudinal interactome dynamics reveals microbial antagonism during exacerbation, which resolves following treatment in an otherwise stable multi-biome. Assessment of the Pseudomonas interactome shows that interaction networks, rather than abundance alone, are associated with exacerbation risk, and that incorporation of microbial interaction data improves clinical prediction models. Shotgun metagenomic sequencing of an independent cohort validated the multi-biome interactions detected in targeted analysis and confirmed the association with exacerbation. Integrative microbiomics captures microbial interactions to determine exacerbation risk, which cannot be appreciated by the study of a single microbial group. Antibiotic strategies probably target the interaction networks rather than individual microbes, providing a fresh approach to the understanding of respiratory infection.
Mah, D, Chamoli, U & Smith, GCS 2021, 'Usefulness of computed tomography based three-dimensional reconstructions to assess the critical shoulder angle', World Journal of Orthopedics, vol. 12, no. 5, pp. 301-309.
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BACKGROUND: The critical shoulder angle (CSA) is a radiographic measurement that provides an assessment of both glenoid inclination and acromial length. Higher values may correlate with the presence of rotator cuff tears. However, it is difficult to obtain a high-quality true anteroposterior (AP) radiograph of the shoulder, with any excess scapular version or flexion/extension resulting in deviation from the true CSA value. Three-dimensional (3D) bony reconstructions of computed tomography (CT) shoulder scans may be able to be rotated to obtain a similar view to that of true AP radiographs. AIM: To compare CSA measurements performed on 3D bony CT reconstructions, with those on corresponding true AP radiographs. METHODS: CT shoulder scans were matched with true AP radiographs that were classified as either Suter-Henninger type A or C quality. 3D bony reconstructions were segmented from the CT scans, and rotated to replicate an ideal true AP view. Two observers performed CSA measurements using both CT and radiographic images. Measurements were repeated after a one week interval. Reliability was assessed using intraclass correlation coefficients (ICCs) and Bland-Altman plots [bias, limits of agreement (LOA)]. RESULTS: Twenty CT shoulder scans were matched. The mean CSA values were 32.55° (± 4.26°) with radiographs and 29.82° (± 3.49°) with the CT-based method [mean difference 2.73° (± 2.86°); P < 0.001; bias +2.73°; LOA -2.17° to +7.63°]. There was a strong correlation between the two methods (r = 0.748; P < 0.001). Intra-observer reliability was similar, but the best intra-observer values were achieved by the most experienced observer using the CT-based method [ICC: 0.983 (0.958-0.993); bias +0.03°, LOA -1.28° to +1.34°]. Inter-observer reliability was better with the CT-based method [ICC: 0.897 (0.758-0.958), bias +0.24°, LOA -2.93° to +3.41°]. CONCLUSION: The described CT-based method may be a suitable alternative for critical shoulder angle measurement...
Mahmodi, H, Piloni, A, Utama, RH & Kabakova, I 2021, 'Mechanical mapping of bioprinted hydrogel models by brillouin microscopy', Bioprinting, vol. 23, pp. e00151-e00151.
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Three-dimensional (3D) bioprinting has revolutionised the field of biofabrication by delivering precise, cost-effective and a relatively simple way of engineering in vitro living systems in high volume for use in tissue regeneration, biological modelling, drug testing and cell-based diagnostics. The complexity of modern bioprinted systems requires quality control assessment to ensure the resulting product meets the desired criteria of structural design, micromechanical performance and long-term durability. Brillouin microscopy could be an excellent solution for micromechanical assessment of the bioprinted models during or post-fabrication since this technology is non-destructive, label-free and is capable of microscale 3D imaging. In this work, we demonstrate the application of Brillouin microscopy to 3D imaging of hydrogel microstructures created through drop-on-demand bioprinting. In addition, we show that this technology can resolve variations between mechanical properties of the gels with slightly different polymer fractions. This work confirms that Brillouin microscopy can be seen as a characterisation technology complementary to bioprinting, and in the future can be combined within the printer design to achieve simultaneous real-time fabrication and micromechanical characterisation of in vitro biological systems.
Mandwie, M, Karunia, J, Niaz, A, Keay, KA, Musumeci, G, Rennie, C, McGrath, K, Al-Badri, G & Castorina, A 2021, 'Metformin Treatment Attenuates Brain Inflammation and Rescues PACAP/VIP Neuropeptide Alterations in Mice Fed a High-Fat Diet', International Journal of Molecular Sciences, vol. 22, no. 24, pp. 13660-13660.
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High-fat diet (HFD)-induced comorbid cognitive and behavioural impairments are thought to be the result of persistent low-grade neuroinflammation. Metformin, a first-line medication for the treatment of type-2 diabetes, seems to ameliorate these comorbidities, but the underlying mechanism(s) are not clear. Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) are neuroprotective peptides endowed with anti-inflammatory properties. Alterations to the PACAP/VIP system could be pivotal during the development of HFD-induced neuroinflammation. To unveil the pathogenic mechanisms underlying HFD-induced neuroinflammation and assess metformin’s therapeutic activities, (1) we determined if HFD-induced proinflammatory activity was present in vulnerable brain regions associated with the development of comorbid behaviors, (2) investigated if the PACAP/VIP system is altered by HFD, and (3) assessed if metformin rescues such diet-induced neurochemical alterations. C57BL/6J male mice were divided into two groups to receive either standard chow (SC) or HFD for 16 weeks. A further HFD group received metformin (HFD + M) (300 mg/kg BW daily for 5 weeks) via oral gavage. Body weight, fasting glucose, and insulin levels were measured. After 16 weeks, the proinflammatory profile, glial activation markers, and changes within the PI3K/AKT intracellular pathway and the PACAP/VIP system were evaluated by real-time qPCR and/or Western blot in the hypothalamus, hippocampus, prefrontal cortex, and amygdala. Our data showed that HFD causes widespread low-grade neuroinflammation and gliosis, with regional-specific differences across brain regions. HFD also diminished phospho-AKT(Ser473) expression and caused significant disruptions to the PACAP/VIP system. Treatment with metformin attenuated these neuroinflammatory signatures and reversed PI3K/AKT and PACAP/VIP alterations caused by HFD. Altogether, our findings demonstrate that metform...
Maus Esfahani, N, Catchpoole, D & Kennedy, PJ 2021, 'SMCKAT, a Sequential Multi-Dimensional CNV Kernel-Based Association Test', Life, vol. 11, no. 12, pp. 1302-1302.
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Copy number variants (CNVs) are the most common form of structural genetic variation, reflecting the gain or loss of DNA segments compared with a reference genome. Studies have identified CNV association with different diseases. However, the association between the sequential order of CNVs and disease-related traits has not been studied, to our knowledge, and it is still unclear that CNVs function individually or whether they work in coordination with other CNVs to manifest a disease or trait. Consequently, we propose the first such method to test the association between the sequential order of CNVs and diseases. Our sequential multi-dimensional CNV kernel-based association test (SMCKAT) consists of three parts: (1) a single CNV group kernel measuring the similarity between two groups of CNVs; (2) a whole genome group kernel that aggregates several single group kernels to summarize the similarity between CNV groups in a single chromosome or the whole genome; and (3) an association test between the CNV sequential order and disease-related traits using a random effect model. We evaluate SMCKAT on CNV data sets exhibiting rare or common CNVs, demonstrating that it can detect specific biologically relevant chromosomal regions supported by the biomedical literature. We compare the performance of SMCKAT with MCKAT, a multi-dimensional kernel association test. Based on the results, SMCKAT can detect more specific chromosomal regions compared with MCKAT that not only have CNV characteristics, but the CNV order on them are significantly associated with the disease-related trait.
Maus Esfahani, N, Catchpoole, D, Khan, J & Kennedy, PJ 2021, 'MCKAT: a multi-dimensional copy number variant kernel association test', BMC Bioinformatics, vol. 22, no. 1, p. 588.
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AbstractBackgroundCopy number variants (CNVs) are the gain or loss of DNA segments in the genome. Studies have shown that CNVs are linked to various disorders, including autism, intellectual disability, and schizophrenia. Consequently, the interest in studying a possible association of CNVs to specific disease traits is growing. However, due to the specific multi-dimensional characteristics of the CNVs, methods for testing the association between CNVs and the disease-related traits are still underdeveloped. We propose a novel multi-dimensional CNV kernel association test (MCKAT) in this paper. We aim to find significant associations between CNVs and disease-related traits using kernel-based methods.ResultsWe address the multi-dimensionality in CNV characteristics. We first design a single pair CNV kernel, which contains three sub-kernels to summarize the similarity between two CNVs considering all CNV characteristics. Then, aggregate single pair CNV kernel to the whole chromosome CNV kernel, which summarizes the similarity between CNVs in two or more chromosomes. Finally, the association between the CNVs and disease-related traits is evaluated by comparing the similarity in the trait with kernel-based similarity using a score test in a random effect model. We apply MCKAT on genome-wide CNV datasets to examine the association between CNVs and disease-related traits, which demonstrates the potential usefulness the proposed method has for the CNV association tests. We compare the performance of MCKAT with CKAT, a uni-dimensional kernel method. Based on the results, MCKAT indicates stronger evidence, smallerp-value, in detecting significant associations between CNVs and disease-related traits in both rare and common CNV datasets.ConclusionA...
McDonagh, J, Ferguson, C, Prichard, R, Chang, S, Phillips, J, Davidson, P, Macdonald, P & Newton, P 2021, 'Predictive Performance of Six Frailty Instruments in Adults With Heart Failure: 12-month Outcomes From the FRAME-HF Study', Heart, Lung and Circulation, vol. 30, pp. S99-S99.
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McNally, R, Alqudah, A, McErlean, EM, Rennie, C, Morshed, N, Short, A, McGrath, K, Shimoni, O, Robson, T, McCarthy, HO & McClements, L 2021, 'Non-viral gene delivery utilizing RALA modulates sFlt-1 secretion, important for preeclampsia', Nanomedicine, vol. 16, no. 22, pp. 1999-2012.
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Background: Overexpression of sFlt-1 or modulation of FKBPL, key antiangiogenic proteins, are important in the pathogenesis of preeclampsia. Methods: A newly developed nonviral gene-delivery system, RALA, capable of overexpressing sFlt-1 (e15a isoform) was delivered in vivo in transgenic haploinsufficient ( Fkbpl+/−) mice. RALA was also used in vitro to deliver human Flt1 (hFlt1) in trophoblast cells. Results: Serum stable and nontoxic RALA/DNA-based nanoparticles induced an increase in sFlt-1 protein levels in the blood and total protein in the urine; the effect was more pronounced in Fkbpl+/− mice. In vitro, RALA-hFlt nanoparticles significantly reduced secretion of sFlt-1 in trophoblast cells. Conclusion: The RALA-based genetic nanodelivery system can be safely and effectively applied to emulate preeclampsia-like features or reduce sFlt-1 levels in vitro.
Mehta, M, Malyla, V, Paudel, KR, Chellappan, DK, Hansbro, PM, Oliver, BG & Dua, K 2021, 'Berberine loaded liquid crystalline nanostructure inhibits cancer progression in adenocarcinomic human alveolar basal epithelial cells in vitro', Journal of Food Biochemistry, vol. 45, no. 11, p. e13954.
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Metastasis represents the leading cause of death in lung cancer patients. C-X-C Motif Chemokine Ligand 8 (CXCL-8), Chemokine (C-C motif) ligand 20 (CCL-20) and heme oxygenase -1 (HO-1) play an important role in cancer cell proliferation and migration. Berberine is an isoquinoline alkaloid isolated from several herbs in the Papaveraceae family that exhibits anti-inflammatory, anticancer and antidiabetic properties. Therefore, the aim of present study is to investigate the inhibitory potential of berberine monoolein loaded liquid crystalline nanoparticles (berberine-LCNs) against cancer progression. Berberine-LCNs were prepared by mixing berberine, monoolein and poloxamer 407 (P407) using ultrasonication method. A549 cells were treated with or without 5 µM dose of berberine LCNs for 24 hr and total cellular protein was extracted and further analyzed for the protein expression of CCl-20, CXCL-8 and HO-1 using human oncology array kit. Our results showed that berberine-LCNs significantly reduced the expression of CCl-20, CXCL-8 and HO-1 at dose of 5µM. Collectively, our findings suggest that berberine-LCNs have inhibitory effect on inflammation/oxidative stress related cytokines i.e. CCL20, CXCL-8, and HO-1 which could be a novel therapeutic target for the management of lung cancer. PRACTICAL APPLICATIONS: Berberine is an isoquinoline alkaloid extracted from various plants of Papaveraceae family. CXCL-8, CCL-20 and HO-1 play an important role in cancer progression. Our study showed that Berberine LCNs significantly downregulate the expression of CXCL-8, CCL-20 and HO-1 which suggests that Berberine loaded nanoparticles could be a promising therapeutic alternative for the management of lung cancer.
Mehta, M, Paudel, KR, Panth, N, Xenaki, D, Macloughlin, R, Oliver, BG, Lobenberg, R, Hansbro, PM, Chellappan, DK & Dua, K 2021, 'Drug delivery advances in mitigating inflammation via matrix metalloproteinases in respiratory diseases', Nanomedicine, vol. 16, no. 6, pp. 437-439.
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Mehta, M, Paudel, KR, Shukla, SD, Allam, VSRR, Kannaujiya, VK, Panth, N, Das, A, Parihar, VK, Chakraborty, A, Ali, MK, Jha, NK, Xenaki, D, Su, QP, Wich, PR, Adams, J, Hansbro, PM, Chellappan, DK, Oliver, BGG & Dua, K 2021, 'Recent trends of NFκB decoy oligodeoxynucleotide-based nanotherapeutics in lung diseases', Journal of Controlled Release, vol. 337, pp. 629-644.
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Mirzaie, M, Lakzian, E, Khan, A, Warkiani, ME, Mahian, O & Ahmadi, G 2021, 'COVID-19 spread in a classroom equipped with partition – A CFD approach', Journal of Hazardous Materials, vol. 420, pp. 126587-126587.
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In this study, the motion and distribution of droplets containing coronaviruses emitted by coughing of an infected person in front of a classroom (e.g., a teacher) were investigated using CFD. A 3D turbulence model was used to simulate the airflow in the classroom, and a Lagrangian particle trajectory analysis method was used to track the droplets. The numerical model was validated and was used to study the effects of ventilation airflow speeds of 3, 5, and 7 m/s on the dispersion of droplets of different sizes. In particular, the effect of installing transparent barriers in front of the seats on reducing the average droplet concentration was examined. The results showed that using the seat partitions for individuals can prevent the infection to a certain extent. An increase in the ventilation air velocity increased the droplets’ velocities in the airflow direction, simultaneously reducing the trapping time of the droplets by solid barriers. As expected, in the absence of partitions, the closest seats to the infected person had the highest average droplet concentration (3.80 × 10−8 kg/m3 for the case of 3 m/s).
Mitchell, AB, Li, C-X, Oliver, BGG, Holmes, EC & Glanville, AR 2021, 'High-resolution Metatranscriptomic Characterization of the Pulmonary RNA Virome After Lung Transplantation', Transplantation, vol. 105, no. 12, pp. 2546-2553.
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Background. Lung transplantation provides a unique opportunity to investigate the constituents and temporal dynamics of the human pulmonary microbiome after lung transplantation. For methodological reasons, prior studies using metagenomics have detected DNA viruses but not demonstrated the presence of RNA viruses, including those that are common community acquired. In this proof-of-concept study, we aimed to further characterize the pulmonary microbiome after lung transplantation by using metagenomic next-generation sequencing (mNGS), with a particular focus on the RNA virome. Methods. We performed a single-center longitudinal study of lower respiratory tract RNA viruses and bacteria using bronchoalveolar lavage at postoperative day 1 and week 6 analyzed with total RNA sequencing (metatranscriptomics). Five primary and 5 repeat transplant recipients were recruited. Results. mNGS identified 5 RNA viruses (nil in the normal saline control), including 4 species of human rhinovirus not previously reported in Australia: A7 (HRV-A7), C22 (HRV-C22), B52 (HRV-B52), and B72 (HRV-B72). Overall, 12/20 specimens were virus positive in 7/10 cases. Human parainfluenza virus 3 was the most frequent virus in 7/20 specimens in 5/10 cases. In this small study, we did not detect a significant difference in abundance and diversity of RNA viruses and bacteria at postoperative day 1 and 6 wk, nor differences between retransplant recipients and primary lung transplant recipients. Conclusions. Our study demonstrates how mNGS can also identify RNA viruses within the human pulmonary virome, ...
Morshedi Rad, D, Alsadat Rad, M, Razavi Bazaz, S, Kashaninejad, N, Jin, D & Ebrahimi Warkiani, M 2021, 'A Comprehensive Review on Intracellular Delivery', Advanced Materials, vol. 33, no. 13, pp. e2005363-2005363.
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AbstractIntracellular delivery is considered an indispensable process for various studies, ranging from medical applications (cell‐based therapy) to fundamental (genome‐editing) and industrial (biomanufacture) approaches. Conventional macroscale delivery systems critically suffer from such issues as low cell viability, cytotoxicity, and inconsistent material delivery, which have opened up an interest in the development of more efficient intracellular delivery systems. In line with the advances in microfluidics and nanotechnology, intracellular delivery based on micro‐ and nanoengineered platforms has progressed rapidly and held great promises owing to their unique features. These approaches have been advanced to introduce a smorgasbord of diverse cargoes into various cell types with the maximum efficiency and the highest precision. This review differentiates macro‐, micro‐, and nanoengineered approaches for intracellular delivery. The macroengineered delivery platforms are first summarized and then each method is categorized based on whether it employs a carrier‐ or membrane‐disruption‐mediated mechanism to load cargoes inside the cells. Second, particular emphasis is placed on the micro‐ and nanoengineered advances in the delivery of biomolecules inside the cells. Furthermore, the applications and challenges of the established and emerging delivery approaches are summarized. The topic is concluded by evaluating the future perspective of intracellular delivery toward the micro‐ and nanoengineered approaches.
Müller Bark, J, Kulasinghe, A, Hartel, G, Leo, P, Warkiani, ME, Jeffree, RL, Chua, B, Day, BW & Punyadeera, C 2021, 'Isolation of Circulating Tumour Cells in Patients With Glioblastoma Using Spiral Microfluidic Technology – A Pilot Study', Frontiers in Oncology, vol. 11, p. 681130.
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Glioblastoma (GBM) is the most common and aggressive type of tumour arising from the central nervous system. GBM remains an incurable disease despite advancement in therapies, with overall survival of approximately 15 months. Recent literature has highlighted that GBM releases tumoural content which crosses the blood-brain barrier (BBB) and is detected in patients’ blood, such as circulating tumour cells (CTCs). CTCs carry tumour information and have shown promise as prognostic and predictive biomarkers in different cancer types. Currently, there is limited data for the clinical utility of CTCs in GBM. Here, we report the use of spiral microfluidic technology to isolate CTCs from whole blood of newly diagnosed GBM patients before and after surgery, followed by characterization for GFAP, cell-surface vimentin protein expression and EGFR amplification. CTCs were found in 13 out of 20 patients (9/20 before surgery and 11/19 after surgery). Patients with CTC counts equal to 0 after surgery had a significantly longer recurrence-free survival (p=0.0370). This is the first investigation using the spiral microfluidics technology for the enrichment of CTCs from GBM patients and these results support the use of this technology to better understand the clinical value of CTCs in the management of GBM in future studies.
Nagy, Z, Seneviratne, JA, Kanikevich, M, Chang, W, Mayoh, C, Venkat, P, Du, Y, Jiang, C, Salib, A, Koach, J, Carter, DR, Mittra, R, Liu, T, Parker, MW, Cheung, BB & Marshall, GM 2021, 'An ALYREF-MYCN coactivator complex drives neuroblastoma tumorigenesis through effects on USP3 and MYCN stability', Nature Communications, vol. 12, no. 1, pp. 1-20.
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AbstractTo achieve the very high oncoprotein levels required to drive the malignant state cancer cells utilise the ubiquitin proteasome system to upregulate transcription factor levels. Here our analyses identify ALYREF, expressed from the most common genetic copy number variation in neuroblastoma, chromosome 17q21-ter gain as a key regulator of MYCN protein turnover. We show strong co-operativity between ALYREF and MYCN from transgenic models of neuroblastoma in vitro and in vivo. The two proteins form a nuclear coactivator complex which stimulates transcription of the ubiquitin specific peptidase 3, USP3. We show that increased USP3 levels reduce K-48- and K-63-linked ubiquitination of MYCN, thus driving up MYCN protein stability. In the MYCN-ALYREF-USP3 signal, ALYREF is required for MYCN effects on the malignant phenotype and that of USP3 on MYCN stability. This data defines a MYCN oncoprotein dependency state which provides a rationale for future pharmacological studies.
Nemani, SSP, Vermeulen, CJ, Pech, M, Faiz, A, Oliver, BGG, van den Berge, M, Burgess, JK, Kopp, MV & Weckmann, M 2021, 'COL4A3 expression in asthmatic epithelium depends on intronic methylation and ZNF263 binding', ERJ Open Research, vol. 7, no. 2, pp. 00802-2020.
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BackgroundReduction of COL4A3, one of the six isoforms of collagen 4, in asthmatic airways results in increased inflammation and angiogenesis, implicating it as a central part of asthma pathogenesis. However, to date, the path underlying these diminished COL4A3 levels has been elusive. This study investigated a possible mechanism underlying the reduction of COL4A3 expression.MethodsBronchial biopsies of 76 patients with asthma and 83 controls were subjected to RNA-sequencing and DNA methylation bead arrays to identify expression and methylation changes. The binding of ZNF263 was analysed by chromatin-immunoprecipitation sequencing coupled with quantitative (q)PCR. Effects of ZNF263 silencing, using small interfering RNA, on the COL4A3 expression were studied using qPCR.ResultsCOL4A3 expression was significantly reduced in bronchial biopsies compared to healthy controls, whereas DNA methylation levels at cg11797365 were increased. COL4A3 expression levels were significantly low in asthmatics without inhaled corticosteroid (ICS) use, whereas the expression was not statistically different between asthmatics using ICS and controls. Methylation levels at cg11797365 in vitro were increased upon consecutive rhinovirus infections.ConclusionOur data indicate an epigenetic modification as a contributing factor for the loss of COL4A3 expression in asthmatic airway epithelium.
Ngo, CQ, Chai, R, Jones, TW & Nguyen, HT 2021, 'The Effect of Hypoglycemia on Spectral Moments in EEG Epochs of Different Durations in Type 1 Diabetes Patients', IEEE Journal of Biomedical and Health Informatics, vol. 25, no. 8, pp. 2857-2865.
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The potential of using an electroencephalogram (EEG) to detect hypoglycemia in patients with type 1 diabetes (T1D) has been investigated in both time and frequency domains. Under hyperinsulinemic hypoglycemic clamp conditions, we have shown that the brain's response to hypoglycemic episodes could be described by the centroid frequency and spectral gyration radius evaluated from spectral moments of EEG signals. The aim of this paper is to investigate the effect of hypoglycemia on spectral moments in EEG epochs of different durations and to propose the optimal time window for hypoglycemia detection without using clamp protocols. The incidence of hypoglycemic episodes at night time in five T1D adolescents was analyzed from selected data of ten days of observations in this study. We found that hypoglycemia is associated with significant changes (P < 0.05) in spectral moments of EEG segments in different lengths. Specifically, the changes were more pronounced on the occipital lobe. We used effect size as a measure to determine the best EEG epoch duration for the detection of hypoglycemic episodes. Using Bayesian neural networks, this study showed that 30 second segments provide the best detection rate of hypoglycemia. In addition, Clarke's error grid analysis confirms the correlation between hypoglycemia and EEG spectral moments of this optimal time window, with 86% of clinically acceptable estimated blood glucose values. These results confirm the potential of using EEG spectral moments to detect the occurrence of hypoglycemia.
Nguyen, HG, Le, NV, Nguyen-Duong, KH, Ho-Pham, LT & Nguyen, TV 2021, 'Reference values of body composition parameters for Vietnamese men and women', European Journal of Clinical Nutrition, vol. 75, no. 8, pp. 1283-1290.
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Nguyen, HG, Lieu, KB, Ho-Le, TP, Ho-Pham, LT & Nguyen, TV 2021, 'Discordance between quantitative ultrasound and dual-energy X-ray absorptiometry in bone mineral density: The Vietnam Osteoporosis Study', Osteoporosis and Sarcopenia, vol. 7, no. 1, pp. 6-10.
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Nguyen, T-D, Musial, K & Gabrys, B 2021, 'AutoWeka4MCPS-AVATAR: Accelerating automated machine learning pipeline composition and optimisation', Expert Systems with Applications, vol. 185, pp. 115643-115643.
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Automated machine learning pipeline (ML) composition and optimisation aim at automating the process of finding the most promising ML pipelines within allocated resources (i.e., time, CPU and memory). Existing methods, such as Bayesian-based and genetic-based optimisation, which are implemented in Auto-Weka, Auto-sklearn and TPOT, evaluate pipelines by executing them. Therefore, the pipeline composition and optimisation of these methods frequently require a tremendous amount of time that prevents them from exploring complex pipelines to find better predictive models. To further explore this research challenge, we have conducted experiments showing that many of the generated pipelines are invalid in the first place, and attempting to execute them is a waste of time and resources. To address this issue, we propose a novel method to evaluate the validity of ML pipelines, without their execution, using a surrogate model (AVATAR). The AVATAR generates a knowledge base by automatically learning the capabilities and effects of ML algorithms on datasets’ characteristics. This knowledge base is used for a simplified mapping from an original ML pipeline to a surrogate model which is a Petri net based pipeline. Instead of executing the original ML pipeline to evaluate its validity, the AVATAR evaluates its surrogate model constructed by capabilities and effects of the ML pipeline components and input/output simplified mappings. Evaluating this surrogate model is less resource-intensive than the execution of the original pipeline. As a result, the AVATAR enables the pipeline composition and optimisation methods to evaluate more pipelines by quickly rejecting invalid pipelines. We integrate the AVATAR into the sequential model-based algorithm configuration (SMAC). Our experiments show that when SMAC employs AVATAR, it finds better solutions than on its own. This is down to the fact that the AVATAR can evaluate more pipelines within the same time budget and allocated resources.
Nguyen, TV 2021, 'Personalized fracture risk assessment: where are we at?', Expert Review of Endocrinology & Metabolism, vol. 16, no. 4, pp. 191-200.
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Introduction: Osteoporotic fracture imposes a significant health care burden globally. Personalized assessment of fracture risk can potentially guide treatment decisions. Over the past decade, a number of risk prediction models, including the Garvan Fracture Risk Calculator (Garvan) and FRAX®, have been developed and implemented in clinical practice. Areas covered: This article reviews recent development and validation results concerning the prognostic performance of the two tools. The main areas of review are the need for personalized fracture risk prediction, purposes of risk prediction, predictive performance in terms of discrimination and calibration, concordance between the Garvan and FRAX tools, genetic profiling for improving predictive performance, and treatment thresholds. In some validation studies, FRAX tended to underestimate fracture by as high as 50%. Studies have shown that the predicted risk from the Garvan tool is highly concordant with clinical decision. Expert opinion: Although there are some discrepancy in fracture risk prediction between Garvan and FRAX, both tools are valid and can aid patients and doctors communicate about risk and make informed decision. The ideal of personalized risk assessment for osteoporosis patients will be realized through the incorporation of genetic profiling into existing fracture risk assessment tools.
Nguyen, TV 2021, 'Uncertain effects of hydroxychloroquine and azithromycin on SARS-Cov-2 viral load', International Journal of Antimicrobial Agents, vol. 57, no. 1, pp. 106169-106169.
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Nguyen, TV & Frost, SA 2021, 'Effect of Steroids on Coronavirus Disease 2019 (COVID-19) Mortality Risk: A Bayesian Interpretation', Clinical Infectious Diseases, vol. 73, no. 7, pp. e1774-e1775.
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Nikshad, A, Aghlmandi, A, Safaralizadeh, R, Aghebati-Maleki, L, Warkiani, ME, Khiavi, FM & Yousefi, M 2021, 'Advances of microfluidic technology in reproductive biology', Life Sciences, vol. 265, pp. 118767-118767.
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According to World Health Organization (WHO) reports about 70 million couples suffer from infertility all over the world. A lot of research groups are working on this issue and have made therapeutic approaches by integrating biology, medicine, genetics, chemistry, psychology, mechanic, and many other branches of science. However, these methods have their own pros and cons. Assisted Reproductive Technologies (ART) has appeared to solve infertility problems. In Vitro Fertilization (IVF), Intracytoplasmic Sperm Injection (ICSI), Intrauterine Insemination (IUI) are the most common and conventional technologies in this regard. There are at least two characteristics of microfluidics, mechanical and biochemical, which can be influential in the field of mammalian gamete and preimplantation embryo biology. These microfluidic characteristics can assist in basic biological studies on sperm, oocyte and preimplantation embryo structure, function and environment. Using microfluidics in sorting sperm, conducting different steps of oocyte selection and preparation, and transferring embryo by passing sub-microliter fluid through microchannels results in low cost and short time. The size and shape of microchannels and the volume of used fluid differs from non-human cells to human cells. The most progressions have been seen in animal models. Results suggest that microfluidic systems will lead to improved efficiencies in assisted reproduction.
Novak, AR, Impellizzeri, FM, Trivedi, A, Coutts, AJ & McCall, A 2021, 'Analysis of the worst-case scenarios in an elite football team: Towards a better understanding and application', Journal of Sports Sciences, vol. 39, no. 16, pp. 1-10.
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This study investigated the variability in the worst-case scenario (WCS) and suggested a framework to improve the definition and guide further investigation. Optical tracking data from 26 male players across 38 matches were analysed to determine the WCS for total distance, high-speed running (>5.5 m.s-1) and sprinting (>7.0 m.s-1) using a 3-minute rolling window. Position, total output, previous epoch, match half, time of occurrence, classification of starter vs substitute, and minutes played were modelled as selected contextual factors hypothesized to have associations with the WCS. Linear mixed effects models were used to account for cross-sectional observations and repeated measures. Unexplained variance remained high (total distance R2 = 0.53, high-speed running R2 = 0.53 and sprinting R2 = 0.40). Intra-individual variability was also high (total distance CV = 4.6-8.2%; high-speed CV = 15.6-37.8% and Sprinting CV = 21.1-76.4%). The WCS defined as the maximal physical load in a given time-window, produces unstable metrics lacking context, with high variability. Furthermore, training drills targetting this metric concurrently across players may not have representative designs and may underprepare athletes for complete match demands and multifaceted WCS scenarios. Using WCS as benchmarks (reproducing similar physical activity for training purposes) is conceptually questionable.
Oliver, BG 2021, 'Food for thought: why is there more airway smooth muscle in asthma?', European Respiratory Journal, vol. 58, no. 5, pp. 2101565-2101565.
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All definitions of asthma include reference to smooth muscle contraction, which manifests as either episodic wheeze, breathlessness, cough, bronchospasm and/or exacerbations. Furthermore, bronchodilators are one of most effective classes of therapeutic for the management of acute exacerbations and long-term treatment of asthma. It is therefore somewhat surprising that the smooth muscle cell is often under researched in comparison to inflammatory and epithelial cells in asthma. This likely relates to the difficulty of obtaining bronchoscopic samples and the expertise required to isolate and grow airway smooth cells in vitro. The in vitro growth of smooth muscle cells from bronchial biopsies was pioneered by the group led by J.L. Black [1]. The first publication from her group characterising airway smooth muscle cells in asthma was published 20 years ago, and described increased proliferation of smooth muscle cells ex vivo from people with asthma. It seems fitting that understanding the cause of this increased proliferation was elegantly investigated by Esteves et al. [2] in this issue of the European Respiratory Journal.
Olson, EM, Akintola, T, Phillips, J, Blasini, M, Haycock, NR, Martinez, PE, Greenspan, JD, Dorsey, SG, Wang, Y & Colloca, L 2021, 'Effects of sex on placebo effects in chronic pain participants: a cross-sectional study', Pain, vol. 162, no. 2, pp. 531-542.
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Abstract Sex-related differences can influence outcomes of randomized clinical trials and may jeopardize the effectiveness of pain management and other therapeutics. Thus, it is essential to understand the mechanistic and translational aspects of sex differences in placebo outcomes. Recently, studies in healthy participants have shed light on how sex-related placebo effects might influence outcomes, yet no research has been conducted in a patient population. Herein, we used a tripartite approach to evaluate the interaction of prior therapeutic experience (eg, conditioning), expectations, and placebo effects in 280 chronic (orofacial) pain patients (215 women). In this cross-sectional study, we assessed sex differences in placebo effects, conditioning as a proxy of prior therapeutic effects, and expectations evaluated before and after the exposure to positive outcomes, taking into account participant–experimenter sex concordance and hormonal levels (estradiol and progesterone assessed in premenopausal women). We used mediation analysis to determine how conditioning strength and expectations impacted sex differences in placebo outcomes. Independent of gonadal hormone levels, women showed stronger placebo effects than men. We also found significant statistical sex differences in the conditioning strength and reinforced expectations whereby reinforced expectations mediated the sex-related placebo effects. In addition, the participant–experimenter sex concordance influenced conditioning strength, reinforced expectations, and placebo effects in women but not in men. Our findings suggest that women experience larger conditioning effects, expectations, and placebo effects emphasizing the need to consider sex as a biological variable when placebo components of any outcomes are part of drug development trials and in pain management.
Papanicolaou, M, He, P, Rutting, S, Ammit, A, Xenaki, D, van Reyk, D & Oliver, BG 2021, 'Extracellular Matrix Oxidised by the Granulocyte Oxidants Hypochlorous and Hypobromous Acid Reduces Lung Fibroblast Adhesion and Proliferation In Vitro', Cells, vol. 10, no. 12, pp. 3351-3351.
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Chronic airway inflammation and oxidative stress play crucial roles in the pathogenesis of chronic inflammatory lung diseases, with airway inflammation being a key driving mechanism of oxidative stress in the lungs. Inflammatory responses in the lungs activate neutrophils and/or eosinophils, leading to the generation of hypohalous acids (HOX). These HOX oxidants can damage the extracellular matrix (ECM) structure and may influence cell–ECM interactions. The ECM of the lung provides structural, mechanical, and biochemical support for cells and determines the airway structure. One of the critical cells in chronic respiratory disease is the fibroblast. Thus, we hypothesised that primary human lung fibroblasts (PHLF) exposed to an oxidised cell-derived ECM will result in functional changes to the PHLF. Here, we show that PHLF adhesion, proliferation, and inflammatory cytokine secretion is affected by exposure to HOX-induced oxidisation of the cell-derived ECM. Furthermore, we investigated the impact on fibroblast function from the presence of haloamines in the ECM. Haloamines are chemical by-products of HOX and, like the HOX, haloamines can also modify the ECM. In conclusion, this study revealed that oxidising the cell-derived ECM might contribute to functional changes in PHLF, a key mechanism behind the pathogenesis of inflammatory lung diseases.
Parker, D, Hudson, P, Tieman, J, Thomas, K, Saward, D & Ivynian, S 2021, 'Evaluation of an online toolkit for carers of people with a life-limiting illness at the end-of-life: health professionals’ perspectives', Australian Journal of Primary Health, vol. 27, no. 6, pp. 473-478.
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Carers of people with a life-limiting illness report unmet information, practical, and emotional support needs, and are often unaware of services available to help improve preparedness, wellbeing, and reduce strain. CarerHelp is the first e-health toolkit that focuses on the information and support needs of carers of people with a life-limiting illness at the end-of-life, using a pathway approach. This study investigated the usefulness of CarerHelp, from the perspective of health professionals who care for these people. Through a 10-min online survey, health professionals provided feedback about their user experience and perceived usefulness of the website. Their expert opinion was sought to ascertain whether CarerHelp could increase carers’ preparedness and confidence to support the person for whom they are caring and thereby improve carers’ own psychological wellbeing. Health professionals also evaluated whether CarerHelp adequately raised awareness of support services available. CarerHelp was perceived as a useful resource for increasing preparedness for the caring role, including physical tasks and emotional support. Health professionals reported that CarerHelp would increase carers’ knowledge of services, confidence to care and ability for self-care. Health professionals endorsed CarerHelp as a useful information source, guide for support, and would promote CarerHelp to clients and their families.
Parker, KJ, Phillips, JL, Luckett, T, Agar, M, Ferguson, C & Hickman, LD 2021, 'Analysis of discharge documentation for older adults living with dementia: A cohort study', Journal of Clinical Nursing, vol. 30, no. 23-24, pp. 3634-3643.
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AbstractBackgroundOlder adults living with dementia frequently transition between healthcare settings. Care transitions increase vulnerability and risk of iatrogenic harm.Aim and objectiveTo examine the quality of transitional care arrangements within discharge documentation for older people living with dementia.DesignSecondary analysis of cohort study data.MethodA secondary analysis of the IDEAL Study [ACTRN12612001164886] discharge documents, following the STROBE guidelines. Participants had a confirmed diagnosis of dementia and were discharged from hospital to a nursing home. An audit tool was used to extract the data. This was developed through a synthesis of existing tools and finalised by an expert panel. The analysis assessed the quality of discharge documentation, in the context of transitional care needs, and presented results using descriptive statistics. Functional ability; physical health; cognition and mental health; medications; and socio environmental factors were assessed.ResultsSixty participants were included in analyses, and half were male (52%), with a total participant mean age of 83 (SD 8.7) years. There was wide variability in the quality of core discharge information, ranging from excellent (37%), adequate (43%) to poor (20%). A sub‐group of these core discharge documentation elements that detailed the participants transitional care needs were rated as follows: excellent (17%), adequate (46%) and poor (37%).ConclusionDischarge documentation fails to meet needs of people living with dementia. Improving the quality of discharge documentation for people liv...
Pateetin, P, Hutvagner, G, Bajan, S, Padula, MP, McGowan, EM & Boonyaratanakornkit, V 2021, 'Author Correction: Triple SILAC identified progestin-independent and dependent PRA and PRB interacting partners in breast cancer', Scientific Data, vol. 8, no. 1, p. 145.
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The original version of this Data Descriptor omitted the following author from the Author List: Sarah Bajan. This error has now been corrected in both the PDF and HTML versions of the Article.
Pateetin, P, Hutvagner, G, Bajan, S, Padula, MP, McGowan, EM & Boonyaratanakornkit, V 2021, 'Triple SILAC identified progestin-independent and dependent PRA and PRB interacting partners in breast cancer', Scientific Data, vol. 8, no. 1, p. 100.
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AbstractProgesterone receptor (PR) isoforms, PRA and PRB, act in a progesterone-independent and dependent manner to differentially modulate the biology of breast cancer cells. Here we show that the differences in PRA and PRB structure facilitate the binding of common and distinct protein interacting partners affecting the downstream signaling events of each PR-isoform. Tet-inducible HA-tagged PRA or HA-tagged PRB constructs were expressed in T47DC42 (PR/ER negative) breast cancer cells. Affinity purification coupled with stable isotope labeling of amino acids in cell culture (SILAC) mass spectrometry technique was performed to comprehensively study PRA and PRB interacting partners in both unliganded and liganded conditions. To validate our findings, we applied both forward and reverse SILAC conditions to effectively minimize experimental errors. These datasets will be useful in investigating PRA- and PRB-specific molecular mechanisms and as a database for subsequent experiments to identify novel PRA and PRB interacting proteins that differentially mediated different biological functions in breast cancer.
Patel, D, Taudte, RV, Nizio, K, Herok, G, Cranfield, C & Shimmon, R 2021, 'Headspace analysis of E-cigarette fluids using comprehensive two dimensional GC×GC-TOF-MS reveals the presence of volatile and toxic compounds', Journal of Pharmaceutical and Biomedical Analysis, vol. 196, pp. 113930-113930.
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Peng, H, Zheng, Y, Zhao, Z & Li, J 2021, 'Multigene editing: current approaches and beyond', Briefings in Bioinformatics, vol. 22, no. 5.
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AbstractCRISPR/Cas9 multigene editing is an active and widely studied topic in the fields of biomedicine and biology. It involves a simultaneous participation of multiple single-guide RNAs (sgRNAs) to edit multiple target genes in a way that each gene is edited by one of these sgRNAs. There are possibly numerous sgRNA candidates capable of on-target editing on each of these genes with various efficiencies. Meanwhile, each of these sgRNA candidates may cause unwanted off-target editing at many other genes. Therefore, selection optimization of these multiple sgRNAs is demanded so as to minimize the number of sgRNAs and thus reduce the collective negative effects caused by the off-target editing. This survey reviews wet-laboratory approaches to the implementation of multigene editing and their needs of computational tools for better design. We found that though off-target editing is unavoidable during the gene editing, those disfavored cuttings by some target genes’ sgRNAs can potentially become on-target editing sites for some other genes of interests. This off-to-on role conversion is beneficial to optimize the sgRNA selection in multigene editing. We present a preference cutting score to assess those beneficial off-target cutting sites, which have a few mismatches with their host genes’ on-target editing sites. These potential sgRNAs can be prioritized for recommendation via ranking their on-target average cutting efficiency, the total off-target site number and their average preference cutting score. We also present case studies on cancer-associated genes to demonstrate tremendous usefulness of the new method.
Pham, AK, Miller, M, Rosenthal, P, Das, S, Weng, N, Jang, S, Kurten, RC, Badrani, J, Doherty, TA, Oliver, B & Broide, DH 2021, 'ORMDL3 expression in ASM regulates hypertrophy, hyperplasia via TPM1 and TPM4, and contractility', JCI Insight, vol. 6, no. 7.
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ORM1-like 3 (ORMDL3) has strong genetic linkage to childhood onset asthma. To determine whether ORMDL3 selective expression in airway smooth muscle (ASM) influences ASM function, we used Cre-loxP techniques to generate transgenic mice (hORMDL3Myh11eGFP-cre), which express human ORMDL3 selectively in smooth muscle cells. In vitro studies of ASM cells isolated from the bronchi of hORMDL3Myh11eGFP-cre mice demonstrated that they developed hypertrophy (quantitated by FACS and image analysis), developed hyperplasia (assessed by BrdU incorporation), and expressed increased levels of tropomysin proteins TPM1 and TPM4. siRNA knockdown of TPM1 or TPM4 demonstrated their importance to ORMDL3-mediated ASM proliferation but not hypertrophy. In addition, ASM derived from hORMDL3Myh11eGFP-cre mice had increased contractility to histamine in vitro, which was associated with increased levels of intracellular Ca2+; increased cell surface membrane Orai1 Ca2+ channels, which mediate influx of Ca2+ into the cytoplasm; and increased expression of ASM contractile genes sarco/endoplasmic reticulum Ca2+ ATPase 2b and smooth muscle 22. In vivo studies of hORMDL3Myh11eGFP-cre mice demonstrated that they had a spontaneous increase in ASM and airway hyperreactivity (AHR). ORMDL3 expression in ASM thus induces changes in ASM (hypertrophy, hyperplasia, increased contractility), which may explain the contribution of ORMDL3 to the development of AHR in childhood onset asthma, which is highly linked to ORMDL3 on chromosome 17q12-21.
Pham, DX, Nguyen, HD, Phung, AHT, Bui, TD, Tran, TS, Tran, BNH, Ho-Pham, LT & Nguyen, TV 2021, 'Trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City, Vietnam (1996–2015): a population-based study', BMC Cancer, vol. 21, no. 1, pp. 1-8.
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Abstract Background The burden and trend of thyroid cancer in Vietnam have not been well documented. This study aimed to investigate the trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City from 1996 to 2015. Methods A population-based study retrieved data from the Ho Chi Minh City Cancer Registry during 1996–2015. Trends in the incidence of thyroid cancer were investigated based on age, gender, and histology for each 5-year period. Annual percentage change (APC) in incidence rates was estimated using Joinpoint regression analysis. Results In the study period, there were 5953 thyroid cancer cases (men-to-women ratio 1:4.5) newly diagnosed in Ho Chi Minh City with the mean age of 42.9 years (±14.9 years). The age-standardized incidence rate of thyroid cancer increased from 2.4 per 100,000 during 1996–2000 (95% confidence interval [95% CI]: 2.2–2.6) to 7.5 per 100,000 during 2011–2015 (95% CI: 7.3–7.9), corresponded to an overall APC of 8.7 (95% CI 7.6–9.9). The APC in men and women was 6.2 (95% CI: 4.2–8.2) and 9.2 (95% CI: 8.0–10.4), respectively. The incidence rate in the < 45 years age group was the highest diagnosed overall and increased significantly in both men (APC 11.0) and women (APC 10.1). Both genders shared similar distribution of subtype incidences, with papillary thyroid cancer constituted the most diagnosed (73.3% in men and 85.2% in women). The papillary thyroid cancer observed a markedly increase overall (APC of 10.7 (95% CI 9.3–12.0)). Conclusions There were appreciable increases in...
Philip, J, Collins, A, Phillips, J, Luckett, T, Morgan, DD, Lobb, EA, DiGiacomo, M, Kochovska, S, Brown, L & Currow, DC 2021, 'The Development of the Australian National Palliative Care Clinical Studies Collaborative “Integrating Qualitative Research into Clinical Trials Framework”', Journal of Palliative Medicine, vol. 24, no. 3, pp. 331-337.
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Qualitative methodologies have multiple contributions to health research, including improving baseline understanding in new areas of enquiry; questioning existing assumptions; understanding viewpoints of specific subgroups; and offering complex, contextual information. While the role of qualitative research within mixed methods approaches is well documented, the contribution to clinical trial design and conduct is less well recognized. The Australian Palliative Care Clinical Studies Collaborative and Cancer Symptom Trials have developed a framework to detail how qualitative research might contribute to each key aspect of clinical trials. This practical framework provides real-world examples, including sample qualitative questions, to consider at each phase of controlled clinical trial development. As the number of randomized clinical trials in palliative care increases, a readily accessible approach to integrating qualitative research into clinical trial design and conduct is needed so that its full potential for improving study recruitment, conduct, outcomes, interpretation, and implementation may be realized.
Phillips, JL & Schaefer, I 2021, 'Dying an expected death in prison: a growing reality', International Journal of Palliative Nursing, vol. 27, no. 6, pp. 278-279.
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Polonchuk, L, Surija, L, Lee, MH, Sharma, P, Liu Chung Ming, C, Richter, F, Ben-Sefer, E, Rad, MA, Mahmodi Sheikh Sarmast, H, Shamery, WA, Tran, HA, Vettori, L, Haeusermann, F, Filipe, EC, Rnjak-Kovacina, J, Cox, T, Tipper, J, Kabakova, I & Gentile, C 2021, 'Towards engineering heart tissues from bioprinted cardiac spheroids', Biofabrication, vol. 13, no. 4, pp. 045009-045009.
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Abstract Current in vivo and in vitro models fail to accurately recapitulate the human heart microenvironment for biomedical applications. This study explores the use of cardiac spheroids (CSs) to biofabricate advanced in vitro models of the human heart. CSs were created from human cardiac myocytes, fibroblasts and endothelial cells (ECs), mixed within optimal alginate/gelatin hydrogels and then bioprinted on a microelectrode plate for drug testing. Bioprinted CSs maintained their structure and viability for at least 30 d after printing. Vascular endothelial growth factor (VEGF) promoted EC branching from CSs within hydrogels. Alginate/gelatin-based hydrogels enabled spheroids fusion, which was further facilitated by addition of VEGF. Bioprinted CSs contracted spontaneously and under stimulation, allowing to record contractile and electrical signals on the microelectrode plates for industrial applications. Taken together, our findings indicate that bioprinted CSs can be used to biofabricate human heart tissues for long term in vitro testing. This has the potential to be used to study biochemical, physiological and pharmacological features of human heart tissue.
Poulos, RG, Boon, MY, George, A, Liu, KPY, Mak, M, Maurice, C, Palesy, D, Pont, LG, Poulos, CJ, Ramsey, S, Simpson, P, Steiner, GZ, Villarosa, AR, Watson, K & Parker, D 2021, 'Preparing for an aging Australia: The development of multidisciplinary core competencies for the Australian health and aged care workforce', Gerontology & Geriatrics Education, vol. 42, no. 3, pp. 399-422.
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Appropriately skilled staff are required to meet the health and care needs of aging populations yet, shared competencies for the workforce are lacking. This study aimed to develop multidisciplinary core competencies for health and aged care workers in Australia through a scoping review and Delphi survey. The scoping review identified 28 records which were synthesized through thematic analysis into draft domains and measurable competencies. Consensus was sought from experts over two Delphi rounds (n = 111 invited; n = 59 round one; n = 42 round two). Ten domains with 66 core competencies, to be interpreted and applied according to the worker's scope of practice were finalized. Consensus on multidisciplinary core competencies which are inclusive of a broad range of registered health professionals and unregistered aged care workers was achieved. Shared knowledge, attitudes, and skills across the workforce may improve the standard and coordination of person-centered, integrated care for older Australians from diverse backgrounds.
Pouwels, SD, Hesse, L, Wu, X, Allam, VSRR, van Oldeniel, D, Bhiekharie, LJ, Phipps, S, Oliver, BG, Gosens, R, Sukkar, MB & Heijink, IH 2021, 'LL-37 and HMGB1 induce alveolar damage and reduce lung tissue regeneration via RAGE', American Journal of Physiology-Lung Cellular and Molecular Physiology, vol. 321, no. 4, pp. L641-L652.
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The receptor for advanced glycation end-products (RAGE) has been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). However, it is still unknown whether RAGE directly contributes to alveolar epithelial damage and abnormal repair responses. We hypothesize that RAGE activation not only induces lung tissue damage but also hampers alveolar epithelial repair responses. The effects of the RAGE ligands LL-37 and HMGB1 were examined on airway inflammation and alveolar tissue damage in wild-type and RAGE-deficient mice and on lung damage and repair responses using murine precision cut lung slices (PCLS) and organoids. In addition, their effects were studied on the repair response of human alveolar epithelial A549 cells, using siRNA knockdown of RAGE and treatment with the RAGE inhibitor FPS-ZM1. We observed that intranasal installation of LL-37 and HMGB1 induces RAGE-dependent inflammation and severe alveolar tissue damage in mice within 6 h, with stronger effects in a mouse strain susceptible for emphysema compared with a nonsusceptible strain. In PCLS, RAGE inhibition reduced the recovery from elastase-induced alveolar tissue damage. In organoids, RAGE ligands reduced the organoid-forming efficiency and epithelial differentiation into pneumocyte-organoids. Finally, in A549 cells, we confirmed the role of RAGE in impaired repair responses upon exposure to LL-37. Together, our data indicate that activation of RAGE by its ligands LL-37 and HMGB1 induces acute lung tissue damage and that this impedes alveolar epithelial repair, illustrating the therapeutic potential of RAGE inhibitors for lung tissue repair in emphysema.
Quinn, AW, Phillips, CR, Violi, JP, Steele, JR, Johnson, MS, Westerhausen, MT & Rodgers, KJ 2021, 'β-Methylamino-L-alanine-induced protein aggregation in vitro and protection by L-serine', Amino Acids, vol. 53, no. 9, pp. 1351-1359.
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The cyanobacterial non-protein amino acid α-amino-β-methylaminopropionic acid, more commonly known as BMAA, was first discovered in the seeds of the ancient gymnosperm Cycad circinalis (now Cycas micronesica Hill). BMAA was linked to the high incidence of neurological disorders on the island of Guam first reported in the 1950s. BMAA still attracts interest as a possible causative factor in amyotrophic lateral sclerosis (ALS) following the identification of ALS disease clusters associated with living in proximity to lakes with regular cyanobacterial blooms. Since its discovery, BMAA toxicity has been the subject of many in vivo and in vitro studies. A number of mechanisms of toxicity have been proposed including an agonist effect at glutamate receptors, competition with cysteine for transport system xc_ and other mechanisms capable of generating cellular oxidative stress. In addition, a wide range of studies have reported effects related to disturbances in proteostasis including endoplasmic reticulum stress and activation of the unfolded protein response. In the present studies we examine the effects of BMAA on the ubiquitin-proteasome system (UPS) and on chaperone-mediated autophagy (CMA) by measuring levels of ubiquitinated proteins and lamp2a protein levels in a differentiated neuronal cell line exposed to BMAA. The BMAA induced increases in oxidised proteins and the increase in CMA activity reported could be prevented by co-administration of L-serine but not by the two antioxidants examined. These data provide further evidence of a protective role for L-serine against the deleterious effects of BMAA.
Rad, HS, Rad, HS, Shiravand, Y, Radfar, P, Arpon, D, Warkiani, ME, O'Byrne, K & Kulasinghe, A 2021, 'The Pandora’s box of novel technologies that may revolutionize lung cancer', Lung Cancer, vol. 159, pp. 34-41.
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Non-small cell lung cancer (NSCLC) is one of the most common cancers globally and has a 5-year survival rate ~20%. Immunotherapies have demonstrated long-term and durable responses in NSCLC patients, although they appear to be effective in only a subset of patients. A more comprehensive understanding of the underlying tumour biology may contribute to identifying those patients likely to achieve optimal outcomes. Profiling the tumour microenvironment (TME) has shown to be beneficial in addressing fundamental tumour-immune cell interactions. Advances in multiplexing immunohistochemistry and molecular barcoding has led to recent advances in profiling genes and proteins in NSCLC. Here, we review the recent advancements in spatial profiling technologies for the analysis of NSCLC tissue samples to gain new insights and therapeutic options for NSCLC. The combination of spatial transcriptomics combined with advanced imaging is likely to lead to deep insights into NSCLC tissue biology, which can be a powerful tool to predict likelihood of response to therapy.
Rad, HS, Röhl, J, Stylianou, N, Allenby, MC, Bazaz, SR, Warkiani, ME, Guimaraes, FSF, Clifton, VL & Kulasinghe, A 2021, 'The Effects of COVID-19 on the Placenta During Pregnancy', Frontiers in Immunology, vol. 12, p. 743022.
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Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission.
Radfar, P, Bazaz, SR, Mirakhorli, F & Warkiani, ME 2021, 'The role of 3D printing in the fight against COVID-19 outbreak', Journal of 3D Printing in Medicine, vol. 5, no. 1, pp. 51-60.
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Along with the COVID-19 pandemic, urgent needs for medical and specialized products, especially personal protective equipment, has been overwhelming. The conventional production line of medical devices has been challenged by excessive global demand, and the need for an easy, low-cost and rapid fabrication method is felt more than ever. In a scramble to address this shortfall, manufacturers referred to additive manufacturing or 3D printing to fill the gap and increase the production line of medical devices. Various previously/conventionally fabricated designs have been modified and redesigned to suit the 3D printing requirement to fight against COVID-19. In this perspective, various designs accommodated for the current worldwide outbreak of COVID-19 are discussed and how 3D printing could help the global community against the current and future conditions has been explored.
Rafiei, A, Rezaee, A, Hajati, F, Gheisari, S & Golzan, M 2021, 'SSP: Early prediction of sepsis using fully connected LSTM-CNN model', Computers in Biology and Medicine, vol. 128, pp. 104110-104110.
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Background: Sepsis is a life-threatening condition that occurs due to the body's reaction to infections, and it is a leading cause of morbidity and mortality in hospitals. Early prediction of sepsis onset facilitates early interventions that promote the survival of suspected patients. However, reliable and intelligent systems for predicting sepsis are scarce.
Methods: This paper presents a novel technique called Smart Sepsis Predictor (SSP) to predict sepsis onset in patients admitted to an intensive care unit (ICU). SSP is a deep neural network architecture that encompasses long short-term memory (LSTM), convolutional, and fully connected layers to achieve early prediction of sepsis. SSP can work in two modes; Mode 1 uses demographic data and vital signs, and Mode 2 uses laboratory test results in addition to demographic data and vital signs. To evaluate SSP, we have used the 2019 PhysioNet/CinC Challenge dataset, which includes the records of 40,366 patients admitted to the ICU.
Results: To compare SSP with existing state-of-the-art methods, we have measured the accuracy of the SSP in 4-, 8-, and 12-h prediction windows using publicly available data. Our results show that the SSP performance in Mode 1 and Mode 2 is much higher than existing methods, achieving an area under the receiver operating characteristic curve (AUROC) of 0.89 and 0.92, 0.88 and 0.87, and 0.86 and 0.84 for 4 h, 8 h, and 12 h before sepsis onset, respectively.
Conclusions: Using ICU data, sepsis onset can be predicted up to 12 h in advance. Our findings offer an early solution for mitigating the risk of sepsis onset.
Rampinini, E, Martin, M, Bosio, A, Donghi, F, Carlomagno, D, Riggio, M & Coutts, AJ 2021, 'Impact of COVID-19 lockdown on professional soccer players’ match physical activities', Science and Medicine in Football, vol. 5, no. sup1, pp. 44-52.
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AIM: The COVID-19 pandemic forced the 2019–20 Italian Serie A competition to stop and players went into lockdown. During lockdown, players only trained at home, likely having a detrimental effect on players’ physical fitness and capacity. This study investigated the effect of the COVID-19 lockdown on professional soccer players’ match physical activities. METHODS: Match activities of 265 male professional soccer players were assessed in two periods prior to (PRE1 and PRE2) and one period following the lockdown (POST) using a video tracking system. Linear mixed models were used to examine differences between-periods in total (TD), very high-speed (VHS), sprint (SPR), high-acceleration (ACC) and high-deceleration (DEC) distances, considering full match data and data from six 15-min intervals. RESULTS: TD and VHS during POST were lower than the two other competitive periods (p < 0.001, d small-moderate). SPR did not show differences between periods (p > 0.636). ACC and DEC during POST were lower than PRE2 (p < 0.015, d small). Declines in most 15-min intervals after lockdown were observed in TD and VHS. CONCLUSIONS: There were small differences in the temporal distribution of SPR, ACC and DEC at POST. After the COVID-19 lockdown, soccer players’ higher-intensity running activities were similar to those of games played before the lockdown, but TD and VHS decreased, both considering the entire match and 15-min intervals. The temporal distribution of running activities was mostly stable throughout the season.
Rao, A, Zecchin, R, Byth, K, Denniss, AR, Hickman, LD, DiGiacomo, M, Phillips, JL & Newton, PJ 2021, 'The Role of Lifestyle and Cardiovascular Risk Factors in Dropout From an Australian Cardiac Rehabilitation Program. A Longitudinal Cohort Study', Heart, Lung and Circulation, vol. 30, no. 12, pp. 1891-1900.
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BackgroundCardiac rehabilitation (CR) programs reduce the risk of further cardiac events and improve the ability of people living with cardiovascular disease to manage their symptoms. However, many people who experience a cardiac event do not attend or fail to complete their CR program. Little is known about the characteristics of people who drop out compared to those who complete CR.AimsTo identify subgroups of patients attending a cardiac rehabilitation program who are more likely to dropout prior to final assessment by (1) calculating the dropout rate from the program, (2) quantifying the association between dropout and socio-demographic, lifestyle, and cardiovascular risk factors, and (3) identifying independent predictors of dropout.MethodsThe study population is from a large metropolitan teaching hospital in Sydney, Australia, and consists of all participants consecutively enrolled in an outpatient CR program between 2006 and 2017. Items assessed included diagnoses and co-morbidities, quality of life (SF-36), psychological health (DASS-21), lifestyle factors and physical assessment. Dropout was defined as failure to complete the outpatient CR program and post CR assessment.ResultsOf the 3,350 patients enrolled in the CR program, 784 (23.4%; 95%CI: 22.0–24.9%) dropped out prior to completion. The independent predictors of dropout were smoking (OR 2.4; 95%CI: 1.9–3.0), being separated or divorced (OR 2.0; 95%CI: 1.5–2.6), younger age (<55 years) (OR 1.9; 95%CI: 1.6–2.4), obesity (OR 1.6; 95%CI: 1.3–2.0), diabetes (OR 1.6; 95%CI: 1.3–2.0), sedentary lifestyle (OR 1.3; 95%CI: 1.1–1.6) and depressive symptoms (OR 1.3; 95%CI: 1.1–1.6).ConclusionTo improve the CR program completion rate, clinicians need to consider the impact of socio-demographic, lifestyle, and cardiovascular risk factors on their patients’ ability to complete CR. Tailored strategies which target the independent predictors of dropout are required to promote adherence to CR...
Raoufi, MA, Joushani, HAN, Razavi Bazaz, S, Ding, L, Asadnia, M & Ebrahimi Warkiani, M 2021, 'Effects of sample rheology on the equilibrium position of particles and cells within a spiral microfluidic channel', Microfluidics and Nanofluidics, vol. 25, no. 9, pp. 1-13.
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Elasto-inertial migration in non-Newtonian fluids is a rapidly growing field with tremendous potentials for manipulating micron to submicron particles. Previous research attempts were mainly carried out in straight channels due to the complexity of particle migration, solution tuning, and data analysis in elasto-inertial microfluidics. Consequently, the combined effects of Dean drag force and solution rheology on coupled Dean drag elasto-inertial focusing phenomena have not been carefully analyzed. This study delved thoroughly into the combined effects of solution rheology and Dean drag force on elasto-inertial focusing of particles and cells within a spiral microchannel. Polyethylene oxide (PEO) of 1MDa, 2MDa, and 4MDa molecular weights were used to prepare 250, 500, and 1000 ppm non-Newtonian solutions to investigate the focusing behavior of particles and cells over a wide range of flow rates and solution rheologies. Dean coupled elasto-inertial effects were systematically investigated to demonstrate its potentials for position-adjustable and size-tunable particle and cell focusing phenomenon. Various cells and microbeads with diameters ranging from 1 to 17 μm were employed to carefully study the equilibrium position, focusing band, and migration behavior under different elastic, inertial, and Dean conditions. Following the focusing, cell viability, morphology, and growth rate were evaluated which showed cells remained undamaged from viscosity, shear rate, and chemical properties of PEO solutions. We are of the opinion that the current study can provide scientists with a better understanding of focusing phenomena in viscoelastic fluids within spiral microfluidic channels.
Reddy, KD & Oliver, BGG 2021, 'Sex-specific effects of in utero and adult tobacco smoke exposure', American Journal of Physiology-Lung Cellular and Molecular Physiology, vol. 320, no. 1, pp. L63-L72.
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Tobacco smoke has harmful effects on a multiorgan level. Exposure to smoke, whether in utero or environmental, significantly increases susceptibility. This susceptibility has been identified to be divergent between males and females. However, there remains a distinct lack of thorough research into the relationship between sex and exposure to tobacco. Females tend to generate a more significant response than males during adulthood exposure. The intrauterine environment is meticulously controlled, and exposure to tobacco presents a significant factor that contributes to poor health outcomes and susceptibility later in life. Analysis of these effects in relation to the sex of the offspring is yet to be holistically reviewed and summarized. In this review, we will delineate the time-dependent relationship between tobacco smoke exposure and sex-specific disease susceptibility. We further outline possible biological mechanisms that may contribute to the identified pattern.
Reddy, KD, Lan, A, Boudewijn, IM, Rathnayake, SNH, Koppelman, GH, Aliee, H, Theis, F, Oliver, BG, van den Berge, M & Faiz, A 2021, 'Current Smoking Alters Gene Expression and DNA Methylation in the Nasal Epithelium of Patients with Asthma', American Journal of Respiratory Cell and Molecular Biology, vol. 65, no. 4, pp. 366-377.
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Current smoking contributes to worsened asthma prognosis and more severe symptoms and limits the beneficial effects of corticosteroids. As the nasal epithelium can reflect smoking-induced changes in the lower airways, it is a relevant source to investigate changes in gene expression and DNA methylation. This study explores gene expression and DNA methylation changes in current and ex-smokers with asthma. Matched gene expression and epigenome-wide DNA methylation samples collected from nasal brushings of 55 patients enrolled in a clinical trial investigation of current and ex-smoker patients with asthma were analyzed. Differential gene expression and DNA methylation analyses were conducted comparing current smokers with ex-smokers. Expression quantitative trait methylation (eQTM) analysis was completed to explore smoking-relevant genes by CpG sites that differ between current and ex-smokers. To investigate the relevance of the smoking-associated DNA methylation changes for the lower airways, significant CpG sites were explored in bronchial biopsies from patients who had stopped smoking. A total of 809 genes and 18,814 CpG sites were differentially associated with current smoking in the nose. The cis-eQTM analysis uncovered 171 CpG sites with a methylation status associated with smoking-related gene expression, including AHRR, ALDH3A1, CYP1A1, and CYP1B1. The methylation status of CpG sites altered by current smoking reversed with 1 year of smoking cessation. We confirm that current smoking alters epigenetic patterns and affects gene expression in the nasal epithelium of patients with asthma, which is partially reversible in bronchial biopsies after smoking cessation. We demonstrate the ability to discern molecular changes in the nasal epithelium, presenting this as a tool in future investigations into disease-relevant effects of tobacco smoke.
Reid, G, Klebe, S, van Zandwijk, N & George, AM 2021, 'Asbestos and Zeolites: from A to Z via a Common Ion', Chemical Research in Toxicology, vol. 34, no. 4, pp. 936-951.
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Reid, G, Klebe, S, van Zandwijk, N & George, AM 2021, 'Correction to Asbestos and Zeolites: from A to Z via a Common Ion', Chemical Research in Toxicology, vol. 34, no. 6, pp. 1694-1694.
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Rennie, C, Fernandez, R, Donnelly, S & McGrath, KCY 2021, 'The Impact of Helminth Infection on the Incidence of Metabolic Syndrome: A Systematic Review and Meta-Analysis', Frontiers in Endocrinology, vol. 12, p. 728396.
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BackgroundThere are a growing number of publications that report an absence of inflammatory based disease among populations that are endemic to parasitic worms (helminths) demonstrating the ability of these parasites to potentially regulate human immune responses. The aim of this systematic review and meta-analysis was to determine the impact of helminth infection on metabolic outcomes in human populations.MethodsUsing PRISMA guidelines, six databases were searched for studies published up to August 2020. Random effects meta-analysis was performed to estimate pooled proportions with 95% confidence intervals using the Review Manager Software version 5.4.1.ResultsFourteen studies were included in the review. Fasting blood glucose was significantly lower in persons with infection (MD -0.22, 95% CI -0.40- -0.04, P=0.02), HbA1c levels were lower, although not significantly, and prevalence of the metabolic syndrome (P=0.001) and type 2 diabetes was lower (OR 1.03, 95% CI 0.34-3.09, P<0.0001). Infection was negatively associated with type 2 diabetes when comparing person with diabetes to the group without diabetes (OR 0.44, 95% CI 0.29-0.67, P=0.0001).ConclusionsWhile infection with helminths was generally associated with improved metabolic function, there were notable differences in efficacy between parasite species. Based on the data assessed, live infection with S. mansoni resulted in the most significant positive changes to metabolic outcomes.Systematic Review RegistrationWebsite: PROSPERO Identified: CRD42021227619.
Rezaei, M, Radfar, P, Winter, M, McClements, L, Thierry, B & Warkiani, ME 2021, 'Simple-to-Operate Approach for Single Cell Analysis Using a Hydrophobic Surface and Nanosized Droplets', Analytical Chemistry, vol. 93, no. 10, pp. 4584-4592.
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Microfluidics-based technologies for single-cell analysis are becoming increasingly important tools in biological studies. With the increasing sophistication of microfluidics, cellular barcoding techniques, and next-generation sequencing, a more detailed picture of cellular subtype is emerging. Unfortunately, the majority of the methods developed for single-cell analysis are high-throughput and not suitable for rare cell analysis as they require a high input cell number. Here, we report a low-cost and reproducible method for rare single-cell analysis using a highly hydrophobic surface and nanosized static droplets. Our method allows rapid and efficient on-chip single-cell lysis and subsequent collection of genetic materials in nanoliter droplets using a micromanipulator or a laboratory pipette before subsequent genetic analysis. We show precise isolation of single cancer cells with high purity using two different strategies (i- cytospin and ii- static droplet array) for subsequent RNA analysis using droplet digital polymerase chain reaction (PCR) and real-time PCR. Our highly controlled isolation method opens a new avenue for the study of subcellular functional mechanisms, enabling the identification of rare cells of potential functional or pathogenic consequence.
Rezaei, M, Razavi Bazaz, S, Morshedi Rad, D, Shimoni, O, Jin, D, Rawlinson, W & Ebrahimi Warkiani, M 2021, 'A Portable RT-LAMP/CRISPR Machine for Rapid COVID-19 Screening', Biosensors, vol. 11, no. 10, pp. 369-369.
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The COVID-19 pandemic has changed people’s lives and has brought society to a sudden standstill, with lockdowns and social distancing as the preferred preventative measures. To lift these measurements and reduce society’s burden, developing an easy-to-use, rapid, and portable system to detect SARS-CoV-2 is mandatory. To this end, we developed a portable and semi-automated device for SARS-CoV-2 detection based on reverse transcription loop-mediated isothermal amplification followed by a CRISPR/Cas12a reaction. The device contains a heater element mounted on a printed circuit board, a cooler fan, a proportional integral derivative controller to control the temperature, and designated areas for 0.2 mL Eppendorf® PCR tubes. Our system has a limit of detection of 35 copies of the virus per microliter, which is significant and has the capability of being used in crisis centers, mobile laboratories, remote locations, or airports to diagnose individuals infected with SARS-CoV-2. We believe the current methodology that we have implemented in this article is beneficial for the early screening of infectious diseases, in which fast screening with high accuracy is necessary.
Rezcallah, MC, Al-mazi, T & Ammit, AJ 2021, 'Cataloguing the phosphorylation sites of tristetraprolin (TTP): Functional implications for inflammatory diseases', Cellular Signalling, vol. 78, pp. 109868-109868.
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Tristetraprolin (TTP) is a destabilizing mRNA binding protein known to regulate gene expression of a wide variety of targets, including those that control inflammation. TTP expression, regulation and function is controlled by phosphorylation. While the importance of key serine (S) sites (S52 and S178 in mice and S186 in humans) has been recognized, other sites on the hyperphosphorylated TTP protein have more recently emerged as playing an important role in regulating cellular signalling and downstream functions of TTP. In order to propel investigation of TTP and fully exploit its potential as a drug target in inflammatory disease, this review will catalogue TTP phosphorylation sites in both the murine and human TTP protein, the known and unknown roles and functions of these sites, the kinases and phosphatases that act upon TTP and overview methodological approaches to increase our knowledge of this important protein regulated by phosphorylation.
Rhee, H, Navaratnam, A, Oleinikova, I, Gilroy, D, Scuderi, Y, Heathcote, P, Nguyen, T, Wood, S & Ho, KKY 2021, 'A Novel Liver-targeted Testosterone Therapy for Sarcopenia in Androgen Deprived Men With Prostate Cancer', Journal of the Endocrine Society, vol. 5, no. 9.
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Abstract Objective Androgen deprivation therapy (ADT) reduces muscle and bone mass, increasing frailty in men with prostate cancer. The liver mediates the whole body anabolic effects of testosterone. Based on first-pass metabolism, liver-targeted testosterone treatment (LTTT) entails oral delivery of a small dose of testosterone that does not raise peripheral blood testosterone levels. LTTT reduces blood urea and stimulates protein anabolism in hypogonadal men and postmenopausal women. We investigated whether LTTT prevents loss of lean and bone mass during ADT. Method A 6-month, double-blind, placebo-controlled study of testosterone 40 mg/day in 50 men. Primary outcome measures were lean mass and bone mineral content (BMC). Testosterone, urea and prostate-specific antigen (PSA) were monitored. Patients were withdrawn if PSA exceeded 4 ng/mL. Results 42 patients completed the study. Mean (95% CI) testosterone rose during LTTT but not placebo treatment [∆ 2.2 (1.3-3.0) vs −0.7 (−1.5 to 0.2) nmol/L; P < 0.01]. Mean PSA level did not change significantly during either treatment. Blood urea fell [∆ −0.4 (−0.9 to −0.1) mmol/L] during LTTT but not placebo [∆ 0.05 (−0.8 to 0.9) mmol/L]. BMC [∆ 49 (5 to 93) g; P < 0.02] and lean mass [∆ 0.8 (−0.1 to 1.7) kg; P = 0.04) increased compared to placebo. Five patients on LTTT withdrew from increased PSA levels, all returning to baseline levels. Conclusion LTTT shows promise as a simple therapy for pre...
Richards, C, Sesperez, K, Chhor, M, Ghorbanpour, S, Rennie, C, Ming, CLC, Evenhuis, C, Nikolic, V, Orlic, NK, Mikovic, Z, Stefanovic, M, Cakic, Z, McGrath, K, Gentile, C, Bubb, K & McClements, L 2021, 'Characterisation of cardiac health in the reduced uterine perfusion pressure model and a 3D cardiac spheroid model, of preeclampsia', Biology of Sex Differences, vol. 12, no. 1.
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Abstract Background Preeclampsia is a dangerous cardiovascular disorder of pregnancy that leads to an increased risk of future cardiovascular and metabolic disorders. Much of the pathogenesis and mechanisms involved in cardiac health in preeclampsia are unknown. A novel anti-angiogenic protein, FKBPL, is emerging as having a potential role in both preeclampsia and cardiovascular disease (CVD). Therefore, in this study we aimed to characterise cardiac health and FKBPL regulation in the rat reduced uterine perfusion pressure (RUPP) and a 3D cardiac spheroid model of preeclampsia. Methods The RUPP model was induced in pregnant rats and histological analysis performed on the heart, kidney, liver and placenta (n ≥ 6). Picrosirius red staining was performed to quantify collagen I and III deposition in rat hearts, placentae and livers as an indicator of fibrosis. RT-qPCR was used to determine changes in Fkbpl, Icam1, Vcam1, Flt1 and Vegfa mRNA in hearts and/or placentae and ELISA to evaluate cardiac brain natriuretic peptide (BNP45) and FKBPL secretion. Immunofluorescent staining was also conducted to analyse the expression of cardiac FKBPL. Cardiac spheroids were generated using human cardiac fibroblasts and human coronary artery endothelial cells and treated with patient plasma from normotensive controls, early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE); n = 3. FKBPL and CD31 expression was quantified by immunofluorescent labelling. Results The RUPP procedure induced ...
Richardson, E, McEwen, A, Newton-John, T, Manera, K & Jacobs, C 2021, 'The Core Outcome DEvelopment for Carrier Screening (CODECS) study: protocol for development of a core outcome set', Trials, vol. 22, no. 1, pp. 480-11.
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Abstract Background Reproductive genetic carrier screening is a type of genetic testing available to those planning a pregnancy, or during their first trimester, to understand their risk of having a child with a severe genetic condition. There is a lack of consensus for ‘what to measure’ in studies on this intervention, leading to heterogeneity in choice of outcomes and methods of measurement. Such outcome heterogeneity has implications for the quality and comparability of these studies and has led to a lack of robust research evidence in the literature to inform policy and decision-making around the offer of this screening. As reproductive genetic carrier screening becomes increasingly accessible within the general population, it is timely to investigate the outcomes of this intervention. Objectives The development of a core outcome set is an established methodology to address issues with outcome heterogeneity in research. We aim to develop a core outcome set for reproductive genetic carrier screening to clarify and standardise outcomes for research and practice. Methods In accordance with guidance from the COMET (Core Outcome Measures in Effectiveness Trials) Initiative, this study will consist of five steps: (i) a systematic review of quantitative studies, using narrative synthesis to identify previously reported outcomes, their definitions, and methods of measurement; (ii) a systematic review of qualitative studies using content analysis to identify excerpts related to patient experience and perspectives that can be interpreted as outcomes; (iii) semi-structured focus groups and interviews with patients who have undertaken reproductive...
Roberts, AGK, Catchpoole, DR & Kennedy, PJ 2021, 'Identification of differentially distributed gene expression and distinct sets of cancer-related genes identified by changes in mean and variability', NAR Genomics and Bioinformatics, vol. 4, no. 1, pp. 1-14.
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AbstractThere is increasing evidence that changes in the variability or overall distribution of gene expression are important both in normal biology and in diseases, particularly cancer. Genes whose expression differs in variability or distribution without a difference in mean are ignored by traditional differential expression-based analyses. Using a Bayesian hierarchical model that provides tests for both differential variability and differential distribution for bulk RNA-seq data, we report here an investigation into differential variability and distribution in cancer. Analysis of eight paired tumour–normal datasets from The Cancer Genome Atlas confirms that differential variability and distribution are able to identify cancer-related genes. We further demonstrate that differential variability identifies cancer-related genes that are missed by differential expression analysis, and that differential expression and differential variability identify functionally distinct sets of genes. These results suggest that differential variability analysis may provide insights into genetic aspects of cancer that would not be revealed by differential expression, and that differential distribution analysis may allow for more comprehensive identification of cancer-related genes than analyses based on changes in mean or variability alone.
Roche, CD, Iyer, GR, Nguyen, MH, Mabroora, S, Dome, A, Sakr, K, Pawar, R, Lee, V, Wilson, CC & Gentile, C 2021, 'Cardiac Patch Transplantation Instruments for Robotic Minimally Invasive Cardiac Surgery: Initial Proof-of-concept Designs and Surgery in a Porcine Cadaver', Frontiers in Robotics and AI, vol. 8, p. 714356.
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Background: Damaged cardiac tissues could potentially be regenerated by transplanting bioengineered cardiac patches to the heart surface. To be fully paradigm-shifting, such patches may need to be transplanted using minimally invasive robotic cardiac surgery (not only traditional open surgery). Here, we present novel robotic designs, initial prototyping and a new surgical operation for instruments to transplant patches via robotic minimally invasive heart surgery.Methods: Robotic surgical instruments and automated control systems were designed, tested with simulation software and prototyped. Surgical proof-of-concept testing was performed on a pig cadaver.Results: Three robotic instrument designs were developed. The first (called “Claw” for the claw-like patch holder at the tip) operates on a rack and pinion mechanism. The second design (“Shell-Beak”) uses adjustable folding plates and rods with a bevel gear mechanism. The third (“HeartStamp”) utilizes a stamp platform protruding through an adjustable ring. For the HeartStamp, rods run through a cylindrical structure designed to fit a uniportal Video-Assisted Thorascopic Surgery (VATS) surgical port. Designed to work with or without a sterile sheath, the patch is pushed out by the stamp platform as it protrudes. Two instrument robotic control systems were designed, simulated in silico and one of these underwent early ‘sizing and learning’ prototyping as a proof-of-concept. To reflect real surgical conditions, surgery was run “live” and reported exactly (as-it-happened). We successfully picked up, transferred and released a patch onto the heart using the HeartStamp in a pig cadaver model.Conclusion: These world-first designs, early prototypes and a novel surgical operation pave the way for robotic instr...
Rodrigo, N, Chen, H, Pollock, C & Glastras, S 2021, 'Pre-Conception Weight Loss Improves Reproductive, Metabolic and Kidney Health in Obese Mice and Their Offspring', Journal of the Endocrine Society, vol. 5, no. Suppl 1, pp. A322-A323.
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Abstract Background and Aims: An alarming 40% of women of reproductive age have obesity and during pregnancy obesity adversely impacts metabolic health in mothers and offspring. Maternal complications include diabetes, preeclampsia and chronic kidney disease (CKD). Our previous work showed that offspring have increased risks of obesity, diabetes, and CKD. While pre-pregnancy weight optimisation is advocated, evidence of benefits for mother and offspring are lacking. We aimed to determine if weight loss prior to pregnancy, either with diet modification or liraglutide, improves maternal and offspring metabolic outcomes, and reduces kidney complications in obese mothers and the offspring. Methods: C57BL/6 female mice were fed a high-fat-diet (HFD) for 8 weeks and compared to lean chow-fed controls. HFD-fed dams were administered liraglutide (0.3mg/kg, s.c., for 4weeks) or switched to chow, to induce pre-conception weight loss. Pregnancy rates were observed after mating. Maternal anthropometry and glucose tolerance were measured before and after intervention, and at late gestation. Pregnant dams were either culled at gestational day 18–20 with blood and kidney harvested, or allowed to deliver their offspring. Offspring anthropometry, and glucose tolerance were assessed at postnatal week 12 after either HFD or chow feeding. Immunohistochemistry (IHC), western blotting and RT-PCR were used to measure kidney metabolic (FAS, SREBP) and inflammatory markers (CD-68,TGF-b). Results: HFD-fed dams had reduced glucose tolerance compared to chow-fed dams (p<0.0001), and higher expression of renal metabolic and inflammatory markers in late gestation (eg FAS <0.05, TGFb <0.05). Intervention with liraglutide or diet lowered body weight, improving glucose tolerance (both p<0.001), and fecundity. Markers of kidney damage, namely albuminuria and fibronectin (by RT-PCR and IHC) were reduced (both p<0.05). Liraglutide treated mice exhibited greater gestational weight gain than mice swi...
Rouhi, O, Razavi Bazaz, S, Niazmand, H, Mirakhorli, F, Mas-hafi, S, A. Amiri, H, Miansari, M & Ebrahimi Warkiani, M 2021, 'Numerical and Experimental Study of Cross-Sectional Effects on the Mixing Performance of the Spiral Microfluidics', Micromachines, vol. 12, no. 12, pp. 1470-1470.
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Mixing at the microscale is of great importance for various applications ranging from biological and chemical synthesis to drug delivery. Among the numerous types of micromixers that have been developed, planar passive spiral micromixers have gained considerable interest due to their ease of fabrication and integration into complex miniaturized systems. However, less attention has been paid to non-planar spiral micromixers with various cross-sections and the effects of these cross-sections on the total performance of the micromixer. Here, mixing performance in a spiral micromixer with different channel cross-sections is evaluated experimentally and numerically in the Re range of 0.001 to 50. The accuracy of the 3D-finite element model was first verified at different flow rates by tracking the mixing index across the loops, which were directly proportional to the spiral radius and were hence also proportional to the Dean flow. It is shown that higher flow rates induce stronger vortices compared to lower flow rates; thus, fewer loops are required for efficient mixing. The numerical study revealed that a large-angle outward trapezoidal cross-section provides the highest mixing performance, reaching efficiencies of up to 95%. Moreover, the velocity/vorticity along the channel length was analyzed and discussed to evaluate channel mixing performance. A relatively low pressure drop (<130 kPa) makes these passive spiral micromixers ideal candidates for various lab-on-chip applications.
Rozova, VS, Anwer, AG, Guller, AE, Es, HA, Khabir, Z, Sokolova, AI, Gavrilov, MU, Goldys, EM, Warkiani, ME, Thiery, JP & Zvyagin, AV 2021, 'Machine learning reveals mesenchymal breast carcinoma cell adaptation in response to matrix stiffness', PLOS Computational Biology, vol. 17, no. 7, pp. e1009193-e1009193.
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Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET), are believed to play key roles in facilitating the metastatic cascade. Metastatic lesions often exhibit a similar epithelial-like state to that of the primary tumour, in particular, by forming carcinoma cell clusters via E-cadherin-mediated junctional complexes. However, the factors enabling mesenchymal-like micrometastatic cells to resume growth and reacquire an epithelial phenotype in the target organ microenvironment remain elusive. In this study, we developed a workflow using image-based cell profiling and machine learning to examine morphological, contextual and molecular states of individual breast carcinoma cells (MDA-MB-231). MDA-MB-231 heterogeneous response to the host organ microenvironment was modelled by substrates with controllable stiffness varying from 0.2kPa (soft tissues) to 64kPa (bone tissues). We identified 3 distinct morphological cell types (morphs) varying from compact round-shaped to flattened irregular-shaped cells with lamellipodia, predominantly populating 2-kPa and >16kPa substrates, respectively. These observations were accompanied by significant changes in E-cadherin and vimentin expression. Furthermore, we demonstrate that the bone-mimicking substrate (64kPa) induced multicellular cluster formation accompanied by E-cadherin cell surface localisation. MDA-MB-231 cells responded to different substrate stiffness by morphological adaptation, changes in proliferation rate and cytoskeleton markers, and cluster formation on bone-mimicking substrate. Our results suggest that the stiffest microenvironment can induce MET.
Ruan, M, Fang, L, Yang, S, Chen, Z, Wu, Y, Qu, X, Zhao, J & Cheng, J 2021, 'Prolonged pituitary downregulation with gonadotropin-releasing hormone agonist improves the live-birth rate: a retrospective cohort study comparing 3 different protocols', Annals of Palliative Medicine, vol. 10, no. 9, pp. 9984-9992.
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Russell, JL, McLean, BD, Impellizzeri, FM, Strack, DS & Coutts, AJ 2021, 'Measuring Physical Demands in Basketball: An Explorative Systematic Review of Practices', Sports Medicine, vol. 51, no. 1, pp. 81-112.
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BACKGROUND:Measuring the physical work and resultant acute psychobiological responses of basketball can help to better understand and inform physical preparation models and improve overall athlete health and performance. Recent advancements in training load monitoring solutions have coincided with increases in the literature describing the physical demands of basketball, but there are currently no reviews that summarize all the available basketball research. Additionally, a thorough appraisal of the load monitoring methodologies and measures used in basketball is lacking in the current literature. This type of critical analysis would allow for consistent comparison between studies to better understand physical demands across the sport. OBJECTIVES:The objective of this systematic review was to assess and critically evaluate the methods and technologies used for monitoring physical demands in competitive basketball athletes. We used the term 'training load' to encompass the physical demands of both training and game activities, with the latter assumed to provide a training stimulus as well. This review aimed to critique methodological inconsistencies, establish operational definitions specific to the sport, and make recommendations for basketball training load monitoring practice and reporting within the literature. METHODS:A systematic review of the literature was performed using EBSCO, PubMed, SCOPUS, and Web of Science to identify studies through March 2020. Electronic databases were searched using terms related to basketball and training load. Records were included if they used a competitive basketball population and incorporated a measure of training load. This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO Registration # CRD42019123603), and approved under the National Basketball Association (NBA) Health Related Research Policy. RESULTS:Electronic and manual searches identified 122 papers...
Rutting, S, Xenaki, D, Reddy, KD, Baraket, M, Chapman, DG, King, GG, Oliver, BG & Tonga, KO 2021, 'Airway smooth muscle cells from severe asthma patients with fixed airflow obstruction are responsive to steroid and bronchodilator treatment in vitro', ERJ Open Research, vol. 7, no. 2, pp. 00117-2021.
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Asthma is characterised by recurrent symptoms associated with variable airflow obstruction and airway hyperresponsiveness, all of which are improved with combination inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) treatment in mild-to-moderate asthma [1]. A proportion of patients however develop fixed airflow obstruction (FAO), despite optimised treatment. FAO is prevalent in up to 60% of patients with severe asthma and is associated with a more rapid decline in lung function and increased symptoms [2]. The underlying mechanisms of FAO in asthma are poorly understood; therefore, development of novel treatment strategies remains a challenge.Airway smooth muscle cells (ASMCs) are the major effector cells of bronchoconstriction in asthma and also contribute to the inflammatory process by secreting pro-inflammatory cytokines and chemokines. Therefore, ASMCs are a major target of both β2-agonist and ICS treatment [3]. Although several studies have suggested that steroid signalling [4] or β2-adrenoceptor (β2AR) signalling may be abnormally regulated in severe asthma [5], it remains unknown whether impaired airway smooth muscle corticosteroid and/or β2-agonist response may contribute to the development of FAO. The aim of this study was to investigate whether primary human ASMCs obtained from severe asthma patients with FAO differ in their response to β2-agonists and corticosteroids compared with asthma patients without FAO and healthy controls. We hypothesised that ASMCs from asthma patients with FAO are less responsive to corticosteroid and β2-agonist treatment than those from patients without FAO
Ryan, S, Crowcroft, S, Kempton, T & Coutts, AJ 2021, 'Associations between refined athlete monitoring measures and individual match performance in professional Australian football', Science and Medicine in Football, vol. 5, no. 3, pp. 1-9.
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The purpose of this study was to assess relationships between measures of training load, training response and neuromuscular performance and changes in individual match performance in professional Australian football. Data were collected from 45 professional Australian footballers from one club during the 2019 competition season. External load was measured by GPS technology. Internal load was measured via session rate of perceived exertion (sRPE). Perceptual wellness was measured via pre-training questionnaires (1–5 Likert scale rating of soreness, sleep, fatigue, stress and motivation). Percentage of maximum speed was calculated relative to individual maximum recorded during preseason testing. Rolling derivative training load measures (7-day and 28-day) were calculated. Principal Component Analysis (PCA) identified eight uncorrelated components. PCA factor loadings were used to calculate summed variable covariates and single variables were chosen from components based on practicality and statistical contribution. Associations between covariates and performance were determined via linear Generalised Estimating Equations. Performance was assessed via Player Ratings from a commercial statistics company. Seven-day total distance, IMA event count and sRPE load showed significant positive relationships with performance (18–23% increase in performance z-score). No other covariates displayed significant associations with performance. Individual relative increases in training load within the 7-day period prior to a match may be beneficial for enhancing individual performance.
Ryan, S, Kempton, T & Coutts, AJ 2021, 'Data Reduction Approaches to Athlete Monitoring in Professional Australian Football', International Journal of Sports Physiology and Performance, vol. 16, no. 1, pp. 59-65.
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Purpose: To apply data reduction methods to athlete-monitoring measures to address the issue of data overload for practitioners of professional Australian football teams. Methods: Data were collected from 45 professional Australian footballers from 1 club during the 2018 Australian Football League season. External load was measured in training and matches by 10-Hz OptimEye S5 and ClearSky T6 GPS units. Internal load was measured via the session rate of perceived exertion method. Perceptual wellness was measured via questionnaires completed before training sessions with players providing a rating (1–5 Likert scale) of muscle soreness, sleep quality, fatigue, stress, and motivation. Percentage of maximum speed was calculated relative to individual maximum velocity recorded during preseason testing. Derivative external training load measures (total daily, weekly, and monthly) were calculated. Principal-component analyses (PCAs) were conducted for Daily and Chronic measures, and components were identified via scree plot inspection (eigenvalue > 1). Components underwent orthogonal rotation with a factor loading redundancy threshold of 0.70. Results: The Daily PCA identified components representing external load, perceived wellness, and internal load. The Chronic PCA identified components representing 28-d speed exposure, 28-d external load, 7-d external load, and 28-d internal load. Perceived soreness did not meet the redundancy threshold. Conclusions: Monitoring player exposure to maximum speed is more appropriate over chronic than short time frames to capture variations in between-matches training-cycle duration. Perceived soreness represents a distinct element of a player’s perception of wellness. Summed-variable and single-variable approaches are ...
Rzhevskiy, A, Kapitannikova, A, Malinina, P, Volovetsky, A, Aboulkheyr Es, H, Kulasinghe, A, Thiery, JP, Maslennikova, A, Zvyagin, AV & Ebrahimi Warkiani, M 2021, 'Emerging role of circulating tumor cells in immunotherapy', Theranostics, vol. 11, no. 16, pp. 8057-8075.
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Over the last few years, immunotherapy, in particular, immune checkpoint inhibitor therapy, has revolutionized the treatment of several types of cancer. At the same time, the uptake in clinical oncology has been slow owing to the high cost of treatment, associated toxicity profiles and variability of the response to treatment between patients. In response, personalized approaches based on predictive biomarkers have emerged as new tools for patient stratification to achieve effective immunotherapy. Recently, the enumeration and molecular analysis of circulating tumor cells (CTCs) have been highlighted as prognostic biomarkers for the management of cancer patients during chemotherapy and for targeted therapy in a personalized manner. The expression of immune checkpoints on CTCs has been reported in a number of solid tumor types and has provided new insight into cancer immunotherapy management. In this review, we discuss recent advances in the identification of immune checkpoints using CTCs and shed light on the potential applications of CTCs towards the identification of predictive biomarkers for immunotherapy.
Sadeghi Rad, H, Monkman, J, Warkiani, ME, Ladwa, R, O'Byrne, K, Rezaei, N & Kulasinghe, A 2021, 'Understanding the tumor microenvironment for effective immunotherapy', Medicinal Research Reviews, vol. 41, no. 3, pp. 1474-1498.
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AbstractAdvances in immunotherapy have led to durable and long‐term benefits in a subset of patients across a number of solid tumor types. Understanding of the subsets of patients that respond to immune checkpoint inhibitors at the cellular level, and in the context of their tumor microenvironment (TME) is becoming increasingly important. The TME is composed of a heterogeneous milieu of tumor and immune cells. The immune landscape of the TME can inhibit or promote tumor initiation and progression; thus, a deeper understanding of tumor immunity is necessary to develop immunotherapeutic strategies. Recent developments have focused on characterizing the TME immune contexture (type, density, and function) to discover mechanisms and biomarkers that may predict treatment outcomes. This has, in part, been powered by advancements in spatial characterization technologies. In this review article, we address the role of specific immune cells within the TME at various stages of tumor progression and how the immune contexture determinants affecting tumor growth are used therapeutically.
Saini, V, Joglekar, MV, Wong, WKM, Jiang, G, Nassif, NT, Simpson, AM, Ma, RCW, Dalgaard, LT & Hardikar, AA 2021, 'Manipulating cellular microRNAs and analyzing high-dimensional gene expression data using machine learning workflows', STAR Protocols, vol. 2, no. 4, pp. 100910-100910.
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Samardzic, K, Steele, JR, Violi, JP, Colville, A, Mitrovic, SM & Rodgers, KJ 2021, 'Toxicity and bioaccumulation of two non-protein amino acids synthesised by cyanobacteria, β-N-Methylamino-L-alanine (BMAA) and 2,4-diaminobutyric acid (DAB), on a crop plant', Ecotoxicology and Environmental Safety, vol. 208, pp. 111515-111515.
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In order to study the toxicity of the cyanobacterial non-protein amino acids (NPAAs) L-β-N-methylamino-L-alanine (BMAA) and its structural isomer L-2,4-diaminobutyric acid (DAB) in the forage crop plant alfalfa (Medicago sativa), seedlings were exposed to NPAA-containing media for four days. Root growth was significantly inhibited by both treatments. The content of derivatised free and protein-bound BMAA and DAB in seedlings was then analysed by LC-MS/MS. Both NPAAs were detected in free and protein-bound fractions with higher levels detected in free fractions. Compared to shoots, there was approximately tenfold more BMAA and DAB in alfalfa roots. These results suggest that NPAAs might be taken up into crop plants from contaminated irrigation water and enter the food chain. This may present an exposure pathway for NPAAs in humans.
Sansom-Daly, U, Wakefield, C, Ellis, S, McGill, B, Donoghoe, M, Butow, P, Bryant, R, Sawyer, S, Patterson, P, Anazodo, A, Plaster, M, Thompson, K, Holland, L, Osborn, M, Maguire, F, O’Dwyer, C, De Abreu Lourenco, R & Cohn, R 2021, 'Online, Group-Based Psychological Support for Adolescent and Young Adult Cancer Survivors: Results from the Recapture Life Randomized Trial', Cancers, vol. 13, no. 10, pp. 2460-2460.
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Telehealth interventions offer a practical platform to support adolescent and young adult (AYA) cancer survivors’ mental health needs after treatment, yet efficacy data are lacking. We evaluated an online, group-based, videoconferencing-delivered cognitive-behavioral therapy (CBT) intervention (‘Recapture Life’) in a 3-arm randomized-controlled trial comparing Recapture Life with an online peer-support group, and a waitlist control, with the aim of testing its impact on quality of life, emotional distress and healthcare service use. Forty AYAs (Mage = 20.6 years) within 24-months of completing treatment participated, together with 18 support persons. No groupwise impacts were measured immediately after the six-week intervention. However, Recapture Life participants reported using more CBT skills at the six-week follow-up (OR = 5.58, 95% CI = 2.00–15.56, p = 0.001) than peer-support controls. Recapture Life participants reported higher perceived negative impact of cancer, anxiety and depression at 12-month follow-up, compared to peer-support controls. Post-hoc analyses suggested that AYAs who were further from completing cancer treatment responded better to Recapture Life than those who had completed treatment more recently. While online telehealth interventions hold promise, recruitment to this trial was challenging. As the psychological challenges of cancer survivorship are likely to evolve with time, different support models may prove more or less helpful for different sub-groups of AYA survivors at different times.
Sayyadi, N, Zhand, S, Razavi Bazaz, S & Warkiani, ME 2021, 'Affibody Functionalized Beads for the Highly Sensitive Detection of Cancer Cell-Derived Exosomes', International Journal of Molecular Sciences, vol. 22, no. 21, pp. 12014-12014.
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Exosomes belong to the class of extracellular vesicles of endocytic origin, which are regarded as a promising source of cancer biomarkers in liquid biopsy. As a result, an accurate, sensitive, and specific quantification of these nano-sized particles is of significant importance. Affinity-based approaches are recognized as the most valuable technique for exosome isolation and characterization. Indeed, Affibody biomolecules are a type of protein scaffold engineered with small size and enjoy the features of high thermal stability, affinity, and specificity. While the utilization of antibodies, aptamers, and other biologically active substances for exosome detection has been reported widely, there are no reports describing Affibody molecules’ usage for exosome detection. In this study, for the first time, we have proposed a novel strategy of using Affibody functionalized microbeads (AffiBeads) for exosome detection with a high degree of efficiency. As a proof-of-concept, anti-EGFR-AffiBeads were fabricated and applied to capture and detect human lung A549 cancer cell-derived EGFR-positive exosomes using flow cytometry and fluorescent microscopy. Moreover, the capture efficiency of the AffiBeads were compared with its counterpart antibody. Our results showed that the Affibody probe had a detection limit of 15.6 ng exosomes per mL (~12 exosomes per AffiBead). The approach proposed in the current study can be used for sensitive detection of low expression level markers on tumor-derived exosomes, providing a basis for early-stage cancer diagnosis.
Schaefer, I, Heneka, N, Luckett, T, Agar, MR, Chambers, SK, Currow, DC, Halkett, G, Disalvo, D, Amgarth-Duff, I, Anderiesz, C & Phillips, JL 2021, 'Quality of online self-management resources for adults living with primary brain cancer, and their carers: a systematic environmental scan', BMC Palliative Care, vol. 20, no. 1.
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Abstract Background A primary brain cancer diagnosis is a distressing, life changing event. It adversely affects the quality of life for the person living with brain cancer and their families (‘carers’). Timely access to evidence-based information is critical to enabling people living with brain cancer, and their carers, to self-manage the devastating impacts of this disease. Method A systematic environmental scan of web-based resources. A depersonalised search for online English-language resources published from 2009 to December 2019 and designed for adults (> 25 years of age), living with primary brain cancer, was undertaken using the Google search engine. The online information was classified according to: 1) the step on the cancer care continuum; 2) self-management domains (PRISMS taxonomy); 3) basic information disclosure (Silberg criteria); 4) independent quality verification (HonCode); 5) reliability of disease and treatment information (DISCERN Sections 1 and 2); and readability (Flesch-Kincaid reading grade). Results A total of 119 online resources were identified, most originating in England (n = 49); Australia (n = 27); or the USA (n = 27). The majority of resources related to active treatment (n = 76), without addressing recurrence (n = 3), survivorship (n = 1) or palliative care needs (n = 13). Few online resources directly provided self-management advice for adults living with brain cancer or their carers. Just over a fifth (
Sekuboyina, A, Husseini, ME, Bayat, A, Löffler, M, Liebl, H, Li, H, Tetteh, G, Kukacka, J, Payer, C, Stern, D, Urschler, M, Chen, M, Cheng, D, Lessmann, N, Hu, Y, Wang, T, Yang, D, Xu, D, Ambellan, F, Amiranashvili, T, Ehlke, M, Lamecker, H, Lehnert, S, Lirio, M, Olaguer, NPD, Ramm, H, Sahu, M, Tack, A, Zachow, S, Jiang, T, Ma, X, Angerman, C, Wang, X, Brown, K, Kirszenberg, A, Puybareau, É, Chen, D, Bai, Y, Rapazzo, BH, Yeah, T, Zhang, A, Xu, S, Hou, F, He, Z, Zeng, C, Xiangshang, Z, Liming, X, Netherton, TJ, Mumme, RP, Court, LE, Huang, Z, He, C, Wang, L-W, Ling, SH, Huynh, LD, Boutry, N, Jakubícek, R, Chmelík, J, Mulay, S, Sivaprakasam, M, Paetzold, JC, Shit, S, Ezhov, I, Wiestler, B, Glocker, B, Valentinitsch, A, Rempfler, M, Menze, BH & Kirschke, JS 2021, 'VerSe: A Vertebrae labelling and segmentation benchmark for multi-detector CT images.', Medical Image Anal., vol. 73, pp. 102166-102166.
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Vertebral labelling and segmentation are two fundamental tasks in an automated spine processing pipeline. Reliable and accurate processing of spine images is expected to benefit clinical decision support systems for diagnosis, surgery planning, and population-based analysis of spine and bone health. However, designing automated algorithms for spine processing is challenging predominantly due to considerable variations in anatomy and acquisition protocols and due to a severe shortage of publicly available data. Addressing these limitations, the Large Scale Vertebrae Segmentation Challenge (VerSe) was organised in conjunction with the International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) in 2019 and 2020, with a call for algorithms tackling the labelling and segmentation of vertebrae. Two datasets containing a total of 374 multi-detector CT scans from 355 patients were prepared and 4505 vertebrae have individually been annotated at voxel level by a human-machine hybrid algorithm (https://osf.io/nqjyw/, https://osf.io/t98fz/). A total of 25 algorithms were benchmarked on these datasets. In this work, we present the results of this evaluation and further investigate the performance variation at the vertebra level, scan level, and different fields of view. We also evaluate the generalisability of the approaches to an implicit domain shift in data by evaluating the top-performing algorithms of one challenge iteration on data from the other iteration. The principal takeaway from VerSe: the performance of an algorithm in labelling and segmenting a spine scan hinges on its ability to correctly identify vertebrae in cases of rare anatomical variations. The VerSe content and code can be accessed at: https://github.com/anjany/verse.
Semisch-Dieter, OK, Choi, AH, Ben-Nissan, B & Stewart, MP 2021, 'Modifying an Implant: A Mini-review of Dental Implant Biomaterials', BIO Integration, vol. 2, no. 1, pp. 12-21.
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AbstractDental implants have been used as far back as 2000BC, and since then have developed into highly sophisticated solutions for tooth replacement. It is becoming increasingly important for the materials used in dental implants to exhibit and maintain favorable long-term mechanical, biological and more recently, aesthetic properties. This review aims to assess the biomaterials used in modern dental implants, introducing their properties, and concentrating on modifications to improve these biomaterials. Focus is drawn to the prominent biomaterials, titanium (Ti) and zirconia due to their prevalence in implant dentistry. Additionally, novel coatings and materials with potential use as viable improvements or alternatives are reviewed. An effective dental biomaterial should osseointegrate, maintain structural integrity, resist corrosion and infection, and not cause systemic toxicity or cytotoxicity. Current materials such as bioactive glass offer protection against biofilm formation, and when combined with a titanium–zirconium (TiZr) alloy, provide a reliable combination of properties to represent a competitive alternative. Further long-term clinical studies are needed to inform the development of next-generation materials.Significance StatementBiomaterials have become essential for modern implants. A suitable implant biomaterial integrates into the body to perform a key function, whilst minimizing negative immune response. Focusing on dentistry, the use of dental implants for tooth replacement requires a balance between bodily response, mechanical structure and performance, and aesthetics. This mini-review addresses the use of biomaterials in dental implants with significant comparisons drawn between Ti and zirconia. Attention is drawn to optimizing surface modification processes and the additional use of coatings. Alternatives and novel developments are addre...
Sharma, P & Gentile, C 2021, 'Cardiac Spheroids as in vitro Bioengineered Heart Tissues to Study Human Heart Pathophysiology', Journal of Visualized Experiments, vol. 2021, no. 167.
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Despite several advances in cardiac tissue engineering, one of the major challenges to overcome remains the generation of a fully functional vascular network comprising several levels of complexity to provide oxygen and nutrients within bioengineered heart tissues. Our laboratory has developed a three-dimensional in vitro model of the human heart, known as the 'cardiac spheroid' or 'CS'. This presents biochemical, physiological, and pharmacological features typical of the human heart and is generated by co-culturing its three major cell types, such as cardiac myocytes, endothelial cells, and fibroblasts. Human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs or iCMs) are co-cultured at ratios approximating the ones found in vivo with human cardiac fibroblasts (HCFs) and human coronary artery endothelial cells (HCAECs) in hanging drop culture plates for three to four days. The confocal analysis of CSs stained with antibodies against cardiac Troponin T, CD31 and vimentin (markers for cardiac myocytes, endothelial cells and fibroblasts, respectively) shows that CSs present a complex endothelial cell network, resembling the native one found in the human heart. This is confirmed by the 3D rendering analysis of these confocal images. CSs also present extracellular matrix (ECM) proteins typical of the human heart, such as collagen type IV, laminin and fibronectin. Finally, CSs present a contractile activity measured as syncytial contractility closer to the one typical of the human heart compared to CSs that contain iCMs only. When treated with a cardiotoxic anti-cancer agent, such as doxorubicin (DOX, used to treat leukemia, lymphoma and breast cancer), the viability of DOX-treated CSs is significantly reduced at 10 µM genetic and chemical inhibition of endothelial nitric oxide synthase, a downstream target of DOX in HCFs and HCAECs, reduced its toxicity in CSs. Given these unique features, CSs are currently used as in vitro models to study hea...
Sharma, P, Wang, X, Ming, CLC, Vettori, L, Figtree, G, Boyle, A & Gentile, C 2021, 'Advanced Cardiac Models: Considerations for the Bioengineering of Advanced Cardiac In Vitro Models of Myocardial Infarction (Small 15/2021)', Small, vol. 17, no. 15, pp. 2170067-2170067.
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Sharma, P, Wang, X, Ming, CLC, Vettori, L, Figtree, G, Boyle, A & Gentile, C 2021, 'Considerations for the Bioengineering of Advanced Cardiac In Vitro Models of Myocardial Infarction', Small, vol. 17, no. 15, pp. e2003765-2003765.
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AbstractDespite the latest advances in cardiovascular biology and medicine, myocardial infarction (MI) remains one of the major causes of deaths worldwide. While reperfusion of the myocardium is critical to limit the ischemic damage typical of a MI event, it causes detrimental morphological and functional changes known as “reperfusion injury.” This complex scenario is poorly represented in currently available models of ischemia/reperfusion injury, leading to a poor translation of findings from the bench to the bedside. However, more recent bioengineered in vitro models of the human heart represent more clinically relevant tools to prevent and treat MI in patients. These include 3D cultures of cardiac cells, the use of patient‐derived stem cells, and 3D bioprinting technology. This review aims at highlighting the major features typical of a heart attack while comparing current in vitro, ex vivo, and in vivo models. This information has the potential to further guide in developing novel advanced in vitro cardiac models of ischemia/reperfusion injury. It may pave the way for the generation of advanced pathophysiological cardiac models with the potential to develop personalized therapies.
Shell, SJ, Clark, B, Broatch, JR, Slattery, K, Halson, SL & Coutts, AJ 2021, 'Is a Head-Worn Inertial Sensor a Valid Tool to Monitor Swimming?', International Journal of Sports Physiology and Performance, vol. 16, no. 12, pp. 1901-1904.
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Purpose: This study aimed to independently validate a wearable inertial sensor designed to monitor training and performance metrics in swimmers. Methods: A total of 4 male (21 [4] y, 1 national and 3 international) and 6 female (22 [3] y, 1 national and 5 international) swimmers completed 15 training sessions in an outdoor 50-m pool. Swimmers were fitted with a wearable device (TritonWear, 9-axis inertial measurement unit with triaxial accelerometer, gyroscope, and magnetometer), placed under the swim cap on top of the occipital protuberance. Video footage was captured for each session to establish criterion values. Absolute error, standardized effect, and Pearson correlation coefficient were used to determine the validity of the wearable device against video footage for total swim distance, total stroke count, mean stroke count, and mean velocity. A Fisher exact test was used to analyze the accuracy of stroke-type identification. Results: Total swim distance was underestimated by the device relative to video analysis. Absolute error was consistently higher for total and mean stroke count, and mean velocity, relative to video analysis. Across all sessions, the device incorrectly detected total time spent in backstroke, breaststroke, butterfly, and freestyle by 51% (15%). The device did not detect time spent in drill. Intraclass correlation coefficient results demonstrated excellent intrarater reliability between repeated measures across all swimming metrics. Conclusions: The wearable device investigated in this study does not accurately measure distance, stroke count, and velocity swimming metrics or detect stroke type. Its use as a training monitoring tool in swimming is limited.
Shrestha, J, Ryan, ST, Mills, O, Zhand, S, Razavi Bazaz, S, Hansbro, PM, Ghadiri, M & Ebrahimi Warkiani, M 2021, 'A 3D-printed microfluidic platform for simulating the effects of CPAP on the nasal epithelium', Biofabrication, vol. 13, no. 3, pp. 035028-035028.
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Abstract Obstructive sleep apnea (OSA) is a chronic disorder that involves a decrease or complete cessation of airflow during sleep. It occurs when the muscles supporting the soft tissues in the throat relax during sleep, causing narrowing or closure of the upper airway. Sleep apnea is a serious medical condition with an increased risk of cardiovascular complications and impaired quality of life. Continuous positive airway pressure (CPAP) is the most effective treatment for moderate to severe cases of OSA and is effective in mild sleep apnea. However, CPAP therapy is associated with the development of several nasal side effects and is inconvenient for the user, leading to low compliance rates. The effects of CPAP treatment on the upper respiratory system, as well as the pathogenesis of side effects, are incompletely understood and not adequately researched. To better understand the effects of CPAP treatment on the upper respiratory system, we developed an in vitro 3D-printed microfluidic platform. A nasal epithelial cell line, RPMI 2650, was then exposed to certain conditions to mimic the in vivo environment. To create these conditions, the microfluidic device was utilized to expose nasal epithelial cells grown and differentiated at the air–liquid interface. The airflow was similar to what is experienced with CPAP, with pressure ranging between 0 and 20 cm of H2O. Cells exposed to pressure showed decreased barrier integrity, change in cellular shape, and increased cell death (lactate dehydrogenase release into media) compared to unstressed cells. Stressed cells also showed increased secretions of inflammatory markers IL-6 and IL-8 and had increased production of ATP. Our results suggest that stress induced by airflow leads to structural, metabolic, and inflammatory changes in the nasal epithelium, which may be responsible for develo...
Si, L, Eisman, JA, Winzenberg, T, Sanders, KM, Center, JR, Nguyen, TV, Tran, T & Palmer, AJ 2021, 'Development and validation of the risk engine for an Australian Health Economics Model of Osteoporosis', Osteoporosis International, vol. 32, no. 10, pp. 2073-2081.
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The Australian Health Economics Model of Osteoporosis (AusHEMO) has shown good face, internal and cross validities, and can be used to assist healthcare decision-making in Australia. PURPOSE: This study aimed to document and validate the risk engine of the Australian Health Economics Model of Osteoporosis (AusHEMO). METHODS: AusHEMO is a state-transition microsimulation model. The fracture risks were simulated using fracture incidence rates from the Dubbo Osteoporosis Epidemiology Study. The AusHEMO was validated regarding its face, internal and cross validities. Goodness-of-fit analysis was conducted and Lin's coefficient of agreement and mean absolute difference with 95% limits of agreement were reported. RESULTS: The development of AusHEMO followed general and osteoporosis-specific health economics guidelines. AusHEMO showed good face validity regarding the model's structure, evidence, problem formulation and results. In addition, the model has been proven good internal and cross validities in goodness-of-fit test. Lin's coefficient was 0.99, 1 and 0.94 for validation against the fracture incidence rates, Australian life expectancies and residual lifetime fracture risks, respectively. CONCLUSIONS: In summary, the development of the risk engine of AusHEMO followed the best practice for osteoporosis disease modelling and the model has been shown to have good face, internal and cross validities. The AusHEMO can be confidently used to predict long-term fracture-related outcomes and health economic evaluations when costs data are included. Health policy-makers in Australia can use the AusHEMO to select which osteoporosis interventions such as medications and public health interventions represent good value for money.
Siva, S, Bressel, M, Mai, T, Le, H, Vinod, S, de Silva, H, Macdonald, S, Skala, M, Hardcastle, N, Rezo, A, Pryor, D, Gill, S, Higgs, B, Wagenfuehr, K, Montgomery, R, Awad, R, Chesson, B, Eade, T, Wong, W, Sasso, G, De Abreu Lourenco, R, Kron, T, Ball, D, Neeson, P, Bettington, C, Cook, O, Foote, M, Gowda, R, Haas, M, Haynes, NM, Hilder, B, Lao, L, Lim, A, Ludbrook, J, Jansen, T, MacManus, M, McCullough, SA, Moore, A, Ritchie, D, Shaw, M, Sia, J, Syed, F, Tang, C & Trapani, J 2021, 'Single-Fraction vs Multifraction Stereotactic Ablative Body Radiotherapy for Pulmonary Oligometastases (SAFRON II)', JAMA Oncology, vol. 7, no. 10, pp. 1476-1476.
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Skarding, J, Gabrys, B & Musial, K 2021, 'Foundations and Modeling of Dynamic Networks Using Dynamic Graph Neural Networks: A Survey', IEEE Access, vol. 9, pp. 79143-79168.
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Dynamic networks are used in a wide range of fields, including social network analysis, recommender systems and epidemiology. Representing complex networks as structures changing over time allow network models to leverage not only structural but also temporal patterns. However, as dynamic network literature stems from diverse fields and makes use of inconsistent terminology, it is challenging to navigate. Meanwhile, graph neural networks (GNNs) have gained a lot of attention in recent years for their ability to perform well on a range of network science tasks, such as link prediction and node classification. Despite the popularity of graph neural networks and the proven benefits of dynamic network models, there has been little focus on graph neural networks for dynamic networks. To address the challenges resulting from the fact that this research crosses diverse fields as well as to survey dynamic graph neural networks, this work is split into two main parts. First, to address the ambiguity of the dynamic network terminology we establish a foundation of dynamic networks with consistent, detailed terminology and notation. Second, we present a comprehensive survey of dynamic graph neural network models using the proposed terminology.
Slattery, K, Crowcroft, S & Coutts, AJ 2021, 'Innovating Together: Collaborating to Impact Performance', International Journal of Sports Physiology and Performance, vol. 16, no. 10, pp. 1383-1384.
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Smith, C, Cokcetin, N, Truong, T, Harry, E, Hutvagner, G & Bajan, S 2021, 'Cataloguing the small RNA content of honey using next generation sequencing', Food Chemistry: Molecular Sciences, vol. 2, pp. 100014-100014.
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Smith-Merry, J, O'Donovan, M-A, Dew, A, Hemsley, B, Imms, C, Carey, G, Darcy, S, Ellem, K, Gallego, G, Gilroy, J, Guastella, A, Marella, M, McVilly, K & Plumb, J 2021, 'The Future of Disability Research in Australia: Protocol for a Multiphase Research Agenda–Setting Study', JMIR Research Protocols, vol. 11, no. 1, pp. e31126-e31126.
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Background For people with disabilities to live a good life, it is essential that funded research in health and social care addresses their interests, meets their needs, and fills gaps in our understanding of the impact that services, systems, and policies may have on them. Decisions about research funding should be based on an understanding of the research priorities of people with disabilities, their supporters and allies, disability researchers, service providers, and policy makers working in the field. Objective The aim of this protocol is to describe the research design and methods of a large-scale, disability research agenda–setting exercise conducted in 2021 in Australia. Methods The research agenda–setting exercise involves 3 integrated phases of work. In the first phase, a previous audit of disability research in Australia is updated to understand previous research and continuing gaps in the research. Building on this, the second phase involves consultation with stakeholders—people with disabilities and their supporters and family members, the disability workforce, and people working within services and connected sectors (eg, aging, employment, education, and housing), academia, and public policy. Data for the second phase will be gathered as follows: a national web-based survey; a consultation process undertaken through the government and nongovernment sector; and targeted consultation with Aboriginal and Torres Strait Islander people, children with disabilities and their families, people with cognitive disability, and people with complex communication needs. The third phase involves a web-based survey to develop a research agenda based on the outcomes of all pha...
Soleimanian, A, Khalilzadeh, B, Mahdipour, M, Aref, AR, Kalbasi, A, Bazaz, SR, Warkiani, ME, Rashidi, MR & Mahdavi, M 2021, 'An Efficient Graphene Quantum Dots-Based Electrochemical Cytosensor for the Sensitive Recognition of CD123 in Acute Myeloid Leukemia Cells', IEEE Sensors Journal, vol. 21, no. 15, pp. 16451-16463.
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Leukemia stem cells (LSCs) are suitable candidates to be deployed for the diagnosis and therapy of acute myeloid leukemia (AML) patients. In this study, a novel electrochemical cytosensor was designed for the sensitive detection and quantification of KG1a cells as a model of LSCs. The developed cytosensor was based on the overexpression of cell surface protein CD123 by leukemia KG1a cells. For this purpose, the glassy carbon electrode was modified by graphene quantum dots (GQDs), Au nanoparticles, streptavidin coated AuNPs, biotinylated CD123 antibody and target cells. The dense loading of CD123 antibody and electrical enhancement on the modified electrode were carried out using GQDs, this resulting in a sensitive detection of CD123 positive cells within KG1a cells. Step by step preparation of the nanomaterial-based cytosensor and its optimization steps were confirmed by different electrochemical techniques. The field emission scanning electron microscopy (FE-SEM) images also confirmed the proper attachment of the materials and the cells on the surface of the modified electrode. The linear detection range (LDR) and limit of detection (LOD) of the developed electrochemical biosensor were recorded as 1 cell/mL and 1-25 cells/mL, respectively, which is remarkable. Importantly, the present findings are precise and highly selective in the presence of other leukemia cells (NB4, HL60, and U937 cells). Further, the versatility and accuracy of the proposed cytosensor were evaluated using clinical samples. We believe that the cytosensor proposed in this study has the potential to serve as a next generation sensor for the early detection of leukemia stem cells.
Steele, JR, Italiano, CJ, Phillips, CR, Violi, JP, Pu, L, Rodgers, KJ & Padula, MP 2021, 'Misincorporation Proteomics Technologies: A Review', Proteomes, vol. 9, no. 1, pp. 2-2.
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Proteinopathies are diseases caused by factors that affect proteoform conformation. As such, a prevalent hypothesis is that the misincorporation of noncanonical amino acids into a proteoform results in detrimental structures. However, this hypothesis is missing proteomic evidence, specifically the detection of a noncanonical amino acid in a peptide sequence. This review aims to outline the current state of technology that can be used to investigate mistranslations and misincorporations whilst framing the pursuit as Misincorporation Proteomics (MiP). The current availability of technologies explored herein is mass spectrometry, sample enrichment/preparation, data analysis techniques, and the hyphenation of approaches. While many of these technologies show potential, our review reveals a need for further development and refinement of approaches is still required.
Steele, JR, Strange, N, Rodgers, KJ & Padula, MP 2021, 'A Novel Method for Creating a Synthetic L-DOPA Proteome and In Vitro Evidence of Incorporation', Proteomes, vol. 9, no. 2, pp. 24-24.
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Proteinopathies are protein misfolding diseases that have an underlying factor that affects the conformation of proteoforms. A factor hypothesised to play a role in these diseases is the incorporation of non-protein amino acids into proteins, with a key example being the therapeutic drug levodopa. The presence of levodopa as a protein constituent has been explored in several studies, but it has not been examined in a global proteomic manner. This paper provides a proof-of-concept method for enzymatically creating levodopa-containing proteins using the enzyme tyrosinase and provides spectral evidence of in vitro incorporation in addition to the induction of the unfolded protein response due to levodopa.
Sutherland, TC, Ricafrente, A, Gomola, K, O’Brien, BA & Gorrie, CA 2021, 'Neonatal Rats Exhibit a Predominantly Anti-Inflammatory Response following Spinal Cord Injury', Developmental Neuroscience, vol. 43, no. 1, pp. 18-26.
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It has been reported that children may respond better than adults to a spinal cord injury (SCI) of similar severity. There are known biomechanical differences in the developing spinal cord that may contribute to this “infant lesion effect,” but the underlying mechanisms are unknown. Using immunohistochemistry, we have previously demonstrated a different injury progression and immune cell response after a mild thoracic contusion SCI in infant rats, as compared to adult rats. Here, we investigated the acute inflammatory responses using flow cytometry and ELISA at 1 h, 24 h, and 1 week after SCI in neonatal (P7) and adult (9 weeks) rats, and locomotor recovery was examined for 6 weeks after injury. Adult rats exhibited a pronounced pro-inflammatory response characterized by neutrophils and M1-like macrophage infiltration and Th1 cytokine secretion. Neonatal rats exhibited a decreased pro-inflammatory response characterized by a higher proportion of M2-like macrophages and reduced Th1 cytokine responses, as compared to adults. These results suggest that the initial inflammatory response to SCI is predominantly anti-inflammatory in very young animals.
Sutton, N, Ma, N, Yang, JS, Rawlings-Way, O, Brown, D, McAllister, G, Parker, D & Lewis, R 2021, 'Considering the new minimum staffing standards for Australian residential aged care', Australian Health Review, vol. 46, no. 4, pp. 391-397.
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Objective To compare the historical staffing patterns and organisational characteristics of Australian residential aged care facilities (RACFs) against the new minimum staffing standards recommended by the Royal Commission into Aged Care Quality and Safety (RCACQS). Method Retrospective data analysis was used to compare the staffing levels and characteristics of 1705 RACFs (for 4 years, 2016–19) with the three new mandatory staffing requirements. De-identified datasets were provided by the RCACQS, obtained under its legal authority. Results Only 3.8% of RACFs have staffing levels at or above all three requirements. Although many (79.7%) already meet the requirement to have a registered nurse (RN) on-site for morning and afternoon shifts, few have staffing levels above requirements for total direct care per resident per day (10.4%) or care provided by an RN per resident per day (11.1%). Historical levels of on-site RNs, total direct care, and RN care vary significantly across facilities of different size, location and provider scale. Conclusion The new staffing standards, to be mandatory by 2023, prescribe minimum requirements significantly higher than existing levels, particularly in care per resident per day. Each of the three requirements will likely have a differential effect for different types of RACFs. What is known about the topic? International evidence suggests that introducing mandatory minimum staffing standards tends to increase the amount of care provided by staff in residential aged care facilities (RACFs). However, the impact of staffing standards is influenced by the stringency of the minimum threshold relative to existing staffing levels, the capacity of organisations to increase their staffing levels, and the specific way the regulation is formulated. What does this paper add? This paper explores the potential implications of the three national minimum staffing standards, to be in force by October 2023, specifyi...
Syed, MS, Marquis, C, Taylor, R & Warkiani, ME 2021, 'A two-step microengineered system for high-density cell retention from bioreactors', Separation and Purification Technology, vol. 254, pp. 117610-117610.
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Large-scale cell culture processes are required to produce biopharmaceuticals, cells for tissue engineering, and vaccine production while being effective in toxicity testing, gene therapy vector production for cancer research, and drug development. A growing trend in these industries, particularly for suspension cells, involves implementation of continuous cell perfusion processes, which require an aseptic, efficient, cost-effective, and reliable cell separation and retention scheme. Many cell separation techniques (membrane-based systems, lateral displacement devices, and acoustophoresis) have proven to be highly efficient, but suffer from issue of clogging and high cost, limiting their reliability, and thus, their overall feasibility. Some cell retention devices—those based on inertial microfluidics—offer high reliability (i.e., clog-free), but their efficiency reduces at higher cell concentrations. To overcome this apparent trade-off, we report the development of an integrated system consisting of two different membrane-less microfiltration techniques for cell separation from spent cell media. Although it could be adapted to numerous cell culture applications, this system was optimized and tested for suspension-adapted Chinese Hamster Ovary (CHO) cells. As the first step of the cell retention system, a miniaturised hydrocyclone was developed that could separate the cells with macroscopic volume processing rates (~200 mL/min). At this stage, up to 75% of the cells were isolated with minimal (<5%) change in the viability. The remaining cells passed through the overflow of the device and entered to a multiplexed spiral microchannel system, where more than 90% of the remaining cells were recovered, yielding an overall efficiency of up to 95%. The proposed integrated system is thus ideal for continuous and high throughput cell retention even at high cell concentrations (~80 million cells/mL), which is in range of current need in the bioprocessing industry.
Tang, R, Yu, Z, Ma, Y, Wu, Y, Phoebe Chen, Y-P, Wong, L & Li, J 2021, 'Genetic source completeness of HIV-1 circulating recombinant forms (CRFs) predicted by multi-label learning', Bioinformatics, vol. 37, no. 6, pp. 750-758.
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Abstract Motivation Infection with strains of different subtypes and the subsequent crossover reading between the two strands of genomic RNAs by host cells’ reverse transcriptase are the main causes of the vast HIV-1 sequence diversity. Such inter-subtype genomic recombinants can become circulating recombinant forms (CRFs) after widespread transmissions in a population. Complete prediction of all the subtype sources of a CRF strain is a complicated machine learning problem. It is also difficult to understand whether a strain is an emerging new subtype and if so, how to accurately identify the new components of the genetic source. Results We introduce a multi-label learning algorithm for the complete prediction of multiple sources of a CRF sequence as well as the prediction of its chronological number. The prediction is strengthened by a voting of various multi-label learning methods to avoid biased decisions. In our steps, frequency and position features of the sequences are both extracted to capture signature patterns of pure subtypes and CRFs. The method was applied to 7185 HIV-1 sequences, comprising 5530 pure subtype sequences and 1655 CRF sequences. Results have demonstrated that the method can achieve very high accuracy (reaching 99%) in the prediction of the complete set of labels of HIV-1 recombinant forms. A few wrong predictions are actually incomplete predictions, very close to the complete set of genuine labels. Availability and implementation https://github.com/Runbin-tang/The-source-of-HIV-CRFs-prediction.
Tang, T & Li, J 2021, 'Transformation of FASTA files into feature vectors for unsupervised compression of short reads databases', Journal of Bioinformatics and Computational Biology, vol. 19, no. 01, pp. 2050048-2050048.
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FASTA data sets of short reads are usually generated in tens or hundreds for a biomedical study. However, current compression of these data sets is carried out one-by-one without consideration of the inter-similarity between the data sets which can be otherwise exploited to enhance compression performance of de novo compression. We show that clustering these data sets into similar sub-groups for a group-by-group compression can greatly improve the compression performance. Our novel idea is to detect the lexicographically smallest k-mer (k-minimizer) for every read in each data set, and uses these k-mers as features and their frequencies in every data set as feature values to transform these huge data sets each into a characteristic feature vector. Unsupervised clustering algorithms are then applied to these vectors to find similar data sets and merge them. As the amount of common k-mers of similar feature values between two data sets implies an excessive proportion of overlapping reads shared between the two data sets, merging similar data sets creates immense sequence redundancy to boost the compression performance. Experiments confirm that our clustering approach can gain up to 12% improvement over several state-of-the-art algorithms in compressing reads databases consisting of 17–100 data sets (48.57–197.97[Formula: see text]GB).
Tavakoli, J, Geargeflia, S, Tipper, JL & Diwan, AD 2021, 'Magnetic resonance elastography: A non-invasive biomarker for low back pain studies', Biomedical Engineering Advances, vol. 2, pp. 100014-100014.
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Tavakoli, J, Ghahfarokhi, AJ & Tang, Y 2021, 'Aggregation-Induced Emission Fluorescent Gels: Current Trends and Future Perspectives', Topics in Current Chemistry, vol. 379, no. 2.
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Tervonen, HE, Schaffer, AL, Luckett, T, Phillips, J, Litchfield, M, Todd, A & Pearson, S 2021, 'Patterns of opioid use in older people diagnosed with cancer in New South Wales, Australia', Pharmacoepidemiology and Drug Safety, vol. 30, no. 3, pp. 360-370.
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AbstractPurposeOpioids provide effective analgesia for most cancer patients, but little is known about individual‐level opioid use after cancer diagnosis. We examined the patterns of and factors associated with opioid use in older people diagnosed with cancer.MethodsWe used the Department of Veterans' Affairs (DVA) client data linked with the New South Wales (NSW) Cancer Registry and the Repatriation Pharmaceutical Benefits Scheme data. We included people aged ≥65 years diagnosed with cancer in NSW, Australia in 2005 to 2015. We examined patterns of opioid use in the 12 months after cancer diagnosis and used cause‐specific hazards models to examine factors associated with opioid use.ResultsOf 13 527 people diagnosed with cancer, 51% were dispensed opioids after their diagnosis. We observed the highest proportions of use in people diagnosed with pancreas, liver, or lung cancers. Opioid use was associated with female sex, younger age, more advanced degree of cancer spread, opioid use before cancer diagnosis, and multimorbidity. Forty‐four percentages of all people dispensed opioids had a history of opioid use in the 12 months before their cancer diagnosis; these people had higher median number of different opioids and opioid dispensings, and a shorter time to first opioid dispensing than opioid‐naive people.ConclusionOur study suggests that many older cancer patients were dispensed opioids before their cancer diagnosis. Previously opioid‐treated people had more intense opioid use patterns after diagnosis than opioid‐naïve people. Acknowledging the history of opioid use is important as it may complicate pain treatment in clinical practice.
Thoms, J, Truong, P, Subramanian, S, Knezevic, K, Harvey, G, Huang, Y, Seneviratne, J, Carter, D, Joshi, S, Skhinas, J, Chacon, D, Shah, A, de Jong, I, Beck, D, Göttgens, B, Larsson, J, Wong, J, Zanini, F & Pimanda, J 2021, '3034 – DISRUPTION OF A GATA2, TAL1, ERG REGULATORY CIRCUIT PROMOTES ERYTHROID TRANSITION IN HEALTHY AND LEUKEMIC STEM CELLS', Experimental Hematology, vol. 100, pp. S59-S59.
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Thoms, JAI, Truong, P, Subramanian, S, Knezevic, K, Harvey, G, Huang, Y, Seneviratne, JA, Carter, DR, Joshi, S, Skhinas, J, Chacon, D, Shah, A, de Jong, I, Beck, D, Göttgens, B, Larsson, J, Wong, JWH, Zanini, F & Pimanda, JE 2021, 'Disruption of a GATA2-TAL1-ERG regulatory circuit promotes erythroid transition in healthy and leukemic stem cells', Blood, vol. 138, no. 16, pp. 1441-1455.
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Abstract Changes in gene regulation and expression govern orderly transitions from hematopoietic stem cells to terminally differentiated blood cell types. These transitions are disrupted during leukemic transformation, but knowledge of the gene regulatory changes underpinning this process is elusive. We hypothesized that identifying core gene regulatory networks in healthy hematopoietic and leukemic cells could provide insights into network alterations that perturb cell state transitions. A heptad of transcription factors (LYL1, TAL1, LMO2, FLI1, ERG, GATA2, and RUNX1) bind key hematopoietic genes in human CD34+ hematopoietic stem and progenitor cells (HSPCs) and have prognostic significance in acute myeloid leukemia (AML). These factors also form a densely interconnected circuit by binding combinatorially at their own, and each other’s, regulatory elements. However, their mutual regulation during normal hematopoiesis and in AML cells, and how perturbation of their expression levels influences cell fate decisions remains unclear. In this study, we integrated bulk and single-cell data and found that the fully connected heptad circuit identified in healthy HSPCs persists, with only minor alterations in AML, and that chromatin accessibility at key heptad regulatory elements was predictive of cell identity in both healthy progenitors and leukemic cells. The heptad factors GATA2, TAL1, and ERG formed an integrated subcircuit that regulates stem cell-to-erythroid transition in both healthy and leukemic cells. Components of this triad could be manipulated to facilitate erythroid transition providing a proof of concept that such regulatory circuits can be harnessed to promote specific cell-type transitions and overcome dysregulated hematopoiesis.
Thomson, A, Toohey, K & Darcy, S 2021, 'The Political Economy of Mass Sport Participation Legacies From Large-Scale Sport Events: A Conceptual Paper', Journal of Sport Management, vol. 35, no. 4, pp. 352-363.
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Sport event studies have demonstrated that relevant stakeholders must share objectives and coordinate efforts to leverage a large-scale sport event to secure positive legacies. However, the challenging and complex task of collaboration between networks of diverse organizational stakeholders to secure legacies has received little scholarly attention. In this conceptual paper, the authors explore, through a political economy lens, differences between the political economies of sports and sport events pertaining to mass sport participation legacies. The authors focus on the mesolevel and consider how divergences in political economy elements—structure and context, stakeholders and ideas/incentives, and bargaining processes—influence the likelihood of mass sport participation legacies from large-scale sport events. The authors suggest a need for event legacy stakeholders to engage more meaningfully with the complexities surrounding securing mass sport participation legacies. In addition, they provide pragmatic, actionable implications for policy and practice to assist stakeholders in addressing the challenges they face to maximize legacy outcomes.
Travis, G, Haddadi, N, Simpson, AM, Marsh, DJ, McGowan, EM & Nassif, NT 2021, 'Studying the Oncosuppressive Functions of PTENP1 as a ceRNA', Methods in molecular biology (Clifton, N.J.), vol. 2324, pp. 165-185.
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PTENP1 is a processed pseudogene of the tumour suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN). It functions posttranscriptionally to regulate PTEN by acting as a sponge for microRNAs that target PTEN. PTENP1 therefore functions as a competitive endogenous RNA (ceRNA), competing with PTEN for binding of microRNAs (miRNA) and thereby modulating PTEN cellular abundance. Studies of the overexpression of PTENP1 all confirm its oncosuppressive function to be mediated through the suppression of cell proliferation, induction of apoptosis, and inhibition of cell migration and invasion of cancer cells of differing types. These oncosuppressive functions are a direct consequence of miRNA binding by PTENP1 and the subsequent liberation of PTEN from miRNA induced suppression. In this chapter, we will focus initially on the description of a high efficiency transient transfection method to introduce and overexpress PTENP1 in the cell type of interest, followed by accurate methodologies to measure transfection efficiency by flow cytometry. We will then continue to describe two methods to analyze cell proliferation, namely the CCK-8 assay and Click-iT® EdU assay. Due to commonalities in the manifestation of the oncosuppressive effects of PTENP1, mediated through its role as a ceRNA, the methods presented in this chapter will have wide applicability to a variety of different cell types.
Turkewitz, DR, Moghaddasi, S, Alghalayini, A, D'Amario, C, Ali, HM, Wallach, M & Valenzuela, SM 2021, 'Comparative study of His- and Non-His-tagged CLIC proteins, reveals changes in their enzymatic activity', Biochemistry and Biophysics Reports, vol. 26, pp. 101015-101015.
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The chloride intracellular ion channel protein (CLIC) family are a unique set of ion channels that can exist as soluble and integral membrane proteins. New evidence has emerged that demonstrates CLICs' possess oxidoreductase enzymatic activity and may function as either membrane-spanning ion channels or as globular enzymes. To further characterize the enzymatic profile of members of the CLIC family and to expand our understanding of their functions, we expressed and purified recombinant CLIC1, CLIC3, and a non-functional CLIC1-Cys24A mutant using a Histidine tag, bacterial protein expression system. We demonstrate that the presence of the six-polyhistidine tag at the amino terminus of the proteins led to a decrease in their oxidoreductase enzymatic activity compared to their non-His-tagged counterparts, when assessed using 2-hydroxyethyl disulfide as a substrate. These results strongly suggest the six-polyhistidine tag alters CLIC's structure at the N-terminus, which also contains the enzyme active site. It also raises the need for caution in use of His-tagged proteins when assessing oxidoreductase protein enzymatic function.
Ucar, A, Grizzle, JW, Ghaffari, M, Wahde, M, Akin, HL, Baltes, J, Bozma, HI & Miro, JV 2021, 'IEEE Access Special Section Editorial: Real-Time Machine Learning Applications in Mobile Robotics', IEEE Access, vol. 9, pp. 89694-89698.
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Uddin, MB, Chow, CM, Ling, SH & Su, SW 2021, 'A novel algorithm for automatic diagnosis of sleep apnea from airflow and oximetry signals', Physiological Measurement, vol. 42, no. 1, pp. 015001-015001.
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Abstract Objective. Sleep apnea significantly decreases the quality of life. The apnea hypopnea index (AHI) is the main indicator for sleep apnea diagnosis. This study explored a novel automatic algorithm to diagnose sleep apnea from nasal airflow (AF) and pulse oximetry (SpO2) signals. Approach. Of the 988 polysomnography (PSG) records from the sleep heart health study (SHHS), 45 were randomly selected for the development of an algorithm and the remainder for validation (n = 943). The algorithm detects apnea events by a digitization process, following the determination of the peak excursion (peak-to-trough amplitude) from AF envelope. Hypopnea events were determined from the AF envelope and oxygen desaturation with correction to time lag in SpO2. Total sleep time (TST) was estimated from an optimized percentage of artefact-free total recording time. AHI was estimated from the number of detected events divided by the estimated TST. The estimated AHI was compared to the scored SHHS data for performance evaluation. Main results. The validation showed good agreement between the estimated and scored AHI (intraclass correlation coefficient of 0.95 and mean ±95% limits of agreement of −1.6 ±12.5 events h−1). The diagnostic accuracies were found: 90.7%, 91%, and 96.7% for AHI cut-off ≥5, ≥15, and ≥30 respectively. Significance. The new algorithm is accurate over other existing methods for the automatic diagnosis of sleep apnea. It is applicable to any portable sleep screeners especially for the home diagnosis of sleep apnea.
Ulapane, N, Thiyagarajan, K, Miro, JV & Kodagoda, S 2021, 'Surface Representation of Pulsed Eddy Current Sensor Signals for Improved Ferromagnetic Material Thickness Quantification', IEEE Sensors Journal, vol. 21, no. 4, pp. 5413-5422.
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van Ravesteyn, LM, Skinner, IW, Newton-John, T, Ferreira, ML & Verhagen, AP 2021, 'Think twice before starting a new trial; what is the impact of recommendations to stop doing new trials?', Scandinavian Journal of Pain, vol. 21, no. 1, pp. 152-162.
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Abstract Objectives In evidence-based medicine, we base our conclusions on the effectiveness of interventions on the results of high-quality meta-analysis. If a new randomized controlled trial (RCT) is unlikely to change the pooled effect estimate, conducting the new trial is a waste of resources. We evaluated whether recommendations not to conduct further RCTs reduced the number of trials registered for two scenarios. Methods Analysis of registered trials on the World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP). We regarded trial protocols relevant if they evaluated the effectiveness of (1) exercise for chronic low back pain (LBP) and (2) cognitive behavioural therapy (CBT) for chronic pain. We calculated absolute and relative numbers and change of registered trials in a pre-set time window before and after publication of the recommendations, both published in 2012. Results We found 1,574 trials registered in the WHO trial registry for exercise in LBP (459 before 2012; 1,115 after) and 5,037 trials on chronic pain (1,564 before 2012; 3,473 after). Before 2012, 13 trials on exercise for LBP (out of 459) fit the selection criteria, compared to 42 trials (out of 1,115) after, which represents a relative increase of 33%. Twelve trials (out of 1,564) regarding CBT for chronic pain, fit the selection criteria before 2012 and 18 trials (out of 3,473) after, representing a relative decrease of 32%. We found that visibility, media exposure and strength of the r...
Vasilescu, SA, Khorsandi, S, Ding, L, Bazaz, SR, Nosrati, R, Gook, D & Warkiani, ME 2021, 'A microfluidic approach to rapid sperm recovery from heterogeneous cell suspensions', Scientific Reports, vol. 11, no. 1, pp. 1-11.
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AbstractThe isolation of sperm cells from background cell populations and debris is an essential step in all assisted reproductive technologies. Conventional techniques for sperm recovery from testicular sperm extractions stagnate at the sample processing stage, where it can take several hours to identify viable sperm from a background of collateral cells such as white bloods cells (WBCs), red blood cells (RBCs), epithelial cells (ECs) and in some cases cancer cells. Manual identification of sperm from contaminating cells and debris is a tedious and time-consuming operation that can be suitably addressed through inertial microfluidics. Microfluidics has proven an effective technology for high-quality sperm selection based on motility. However, motility-based selection methods cannot cater for viable, non-motile sperm often present in testicular or epididymal sperm extractions and aspirations. This study demonstrates the use of a 3D printed inertial microfluidic device for the separation of sperm cells from a mixed suspension of WBCs, RBCs, ECs, and leukemic cancer cells. This technology presents a 36-fold time improvement for the recovery of sperm cells (> 96%) by separating sperm, RBCS, WBCs, ECs and cancer cells into tight bands in less than 5 min. Furthermore, microfluidic processing of sperm has no impact on sperm parameters; vitality, motility, morphology, or DNA fragmentation of sperm. Applying inertial microfluidics for non-motile sperm recovery can greatly improve the current processing procedure of testicular sperm extractions, simplifying the fertility outcomes for severe forms of male infertility that warrant the surgery.
Vella, A, Clarke, AC, Kempton, T, Ryan, S, Holden, J & Coutts, AJ 2021, 'Possession chain factors influence movement demands in elite Australian football match-play', Science and Medicine in Football, vol. 5, no. 1, pp. 72-78.
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Violi, JP, Bishop, DP, Padula, MP, Westerhausen, MT & Rodgers, KJ 2021, 'Acetonitrile adduct analysis of underivatised amino acids offers improved sensitivity for hydrophilic interaction liquid chromatography tandem mass-spectrometry', Journal of Chromatography A, vol. 1655, pp. 462530-462530.
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LC-MS/MS method development for native amino acid detection can be problematic due to low ionisation efficiencies, in source fragmentation, potential for cluster ion formation and incorrect application of chromatography techniques. This has led to the majority of the scientific community derivatising amino acids for more sensitive analysis. Derivatisation has several benefits including reduced signal-to-noise ratios, more efficient ionisation, and a change in polarity, allowing the use of reverse phase chromatography. However, derivatisation of amino acids can be expensive, requires additional sample preparation steps, is more time consuming and increases sample instability, due to the most derivatised amino acids only be stable for finite amount of time. While showing initial promise, development of reliable hydrophilic interaction liquid chromatography (HILIC) separation methods has presented difficulties for the analyst including irreproducible separation and poor sensitivity. This study aimed to find a means to improve the detection sensitivity of the 20 protein amino acids by HILIC-MS/MS. We describe the use of previously undescribed amino acid-acetonitrile (ACN) adducts to improve detection of 16 out of the 20 amino acids. While all amino acids examined did form an ACN adduct, 4 had low intensity adduct formation compared to their protonated state, 3 of which are classified as basic amino acids. For 15 of the 20 amino acids tested, we used the ACN adduct for both quantification and qualification ions and demonstrated a significant enhancement in signal-to-noise ratio, ranging from 23 to 1762% improvement. Lower LODs, LOQs and lower ranges of linearity were also achieved for these amino acids. The optimised method was applied to a human neuroblastoma cell line (SH-SY5Y) with the potential to be applied to other complex sample types. The improved sensitivity this method offers simplifies sample preparation and reduces the costs of amino acid analysi...
Virdun, C, Luckett, T, Davidson, PM, Lorenz, K & Phillips, J 2021, 'Generating key practice points that enable optimal palliative care in acute hospitals: Results from the OPAL project's mid-point meta-inference', International Journal of Nursing Studies Advances, vol. 3, pp. 100035-100035.
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Walsh, NP, Halson, SL, Sargent, C, Roach, GD, Nédélec, M, Gupta, L, Leeder, J, Fullagar, HH, Coutts, AJ, Edwards, BJ, Pullinger, SA, Robertson, CM, Burniston, JG, Lastella, M, Le Meur, Y, Hausswirth, C, Bender, AM, Grandner, MA & Samuels, CH 2021, 'Sleep and the athlete: narrative review and 2021 expert consensus recommendations', British Journal of Sports Medicine, vol. 55, no. 7, pp. 356-368.
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Elite athletes are particularly susceptible to sleep inadequacies, characterised by habitual short sleep (<7 hours/night) and poor sleep quality (eg, sleep fragmentation). Athletic performance is reduced by a night or more without sleep, but the influence on performance of partial sleep restriction over 1–3 nights, a more real-world scenario, remains unclear. Studies investigating sleep in athletes often suffer from inadequate experimental control, a lack of females and questions concerning the validity of the chosen sleep assessment tools. Research only scratches the surface on how sleep influences athlete health. Studies in the wider population show that habitually sleeping <7 hours/night increases susceptibility to respiratory infection. Fortunately, much is known about the salient risk factors for sleep inadequacy in athletes, enabling targeted interventions. For example, athlete sleep is influenced by sport-specific factors (relating to training, travel and competition) and non-sport factors (eg, female gender, stress and anxiety). This expert consensus culminates with a sleep toolbox for practitioners (eg, covering sleep education and screening) to mitigate these risk factors and optimise athlete sleep. A one-size-fits-all approach to athlete sleep recommendations (eg, 7–9 hours/night) is unlikely ideal for health and performance. We recommend an individualised approach that should consider the athlete’s perceived sleep needs. Research is needed into the benefits of napping and sleep extension (eg, banking sleep).
Wang, B, Chan, Y-L, Li, G, Ho, KF, Anwer, AG, Smith, BJ, Guo, H, Jalaludin, B, Herbert, C, Thomas, PS, Liao, J, Chapman, DG, Foster, PS, Saad, S, Chen, H & Oliver, BG 2021, 'Maternal Particulate Matter Exposure Impairs Lung Health and Is Associated with Mitochondrial Damage', Antioxidants, vol. 10, no. 7, pp. 1029-1029.
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Relatively little is known about the transgenerational effects of chronic maternal exposure to low-level traffic-related air pollution (TRAP) on the offspring lung health, nor are the effects of removing such exposure before pregnancy. Female BALB/c mice were exposed to PM2.5 (PM2.5, 5 µg/day) for 6 weeks before mating and during gestation and lactation; in a subgroup, PM was removed when mating started to model mothers moving to cleaner areas during pregnancy to protect their unborn child (Pre-exposure). Lung pathology was characterised in both dams and offspring. A subcohort of female offspring was also exposed to ovalbumin to model allergic airways disease. PM2.5 and Pre-exposure dams exhibited airways hyper-responsiveness (AHR) with mucus hypersecretion, increased mitochondrial reactive oxygen species (ROS) and mitochondrial dysfunction in the lungs. Female offspring from PM2.5 and Pre-exposure dams displayed AHR with increased lung inflammation and mitochondrial ROS production, while males only displayed increased lung inflammation. After the ovalbumin challenge, AHR was increased in female offspring from PM2.5 dams compared with those from control dams. Using an in vitro model, the mitochondria-targeted antioxidant MitoQ reversed mitochondrial dysfunction by PM stimulation, suggesting that the lung pathology in offspring is driven by dysfunctional mitochondria. In conclusion, chronic exposure to low doses of PM2.5 exerted transgenerational impairment on lung health.
Wang, B, Chen, H, Xenaki, D, Liao, J, Cowie, C & Oliver, BG 2021, 'Differential inflammatory and toxic effects in-vitro of wood smoke and traffic-related particulate matter from Sydney, Australia', Chemosphere, vol. 272, pp. 129616-129616.
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Background
It is well known that PM2.5 generated by traffic or burning wood is pro-inflammatory and induces various adverse health outcomes in humans. In Sydney, New South Wales, Australia, the main anthropogenic contributors to particulate matter (PM) air pollution are wood combustion heaters, on-road vehicles, and coal-fired power stations. However, the relative toxicity of these local sources has not to date been investigated.Method
PM2.5 was collected on filters from the same sampling site in Liverpool, one suburb of Sydney. According to the positive matrix factorisation and collection season, filters were representative of either day with high traffic-related air pollution (TRAP), wood smoke, or both TRAP and woodsmoke (mixed air pollution). The elemental composition of the PM was assessed by accelerator-based ion beam analysis techniques (i.e. PIXE & PIGE) and size by Dynamic Light Scattering. Toxicity and inflammation were assessed in-vitro in human bronchial epithelial cells by measuring interleukin-6 (IL-6), interleukin-8 (IL-8) release, and MTT.Results
Mixed air pollution (TRAP/wood smoke) PM had more nanometer (nm) sized PM than the other two groups. Using an in-vitro model of the lungs, the mixed air pollution PM was the most toxic, whereas the PM from woodsmoke induced greater IL-6 release than TRAP PM. There was no difference in the induction of IL-8 between the three sources of PM.Conclusion
Marked differences occur in the cellular response to PM from different sources, with differences in both toxicity and inflammation.
Wang, H, Roche, CD & Gentile, C 2021, 'Reply to Yurekli et al.', European Journal of Cardio-Thoracic Surgery.
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Wang, L, Zhang, T, Ye, L, Li, JJ & Su, SW 2021, 'An Efficient Calibration Method for Triaxial Gyroscope', IEEE Sensors Journal, vol. 21, no. 18, pp. 19896-19903.
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This paper presents an efficient servomotor-aided calibration method for the triaxial gyroscope. The entire calibration process only requires approximately one minute, and does not require high-precision equipment. This method is based on the idea that the measurement of the gyroscope should be equal to the rotation speed of the servomotor. A six-observation experimental design is proposed to minimize the maximum variance of the estimated scale factors and biases. In addition, a fast converging recursive linear least square estimation method is presented to reduce computational complexity. The simulation results reflect the robustness of the calibration method under normal and extreme conditions. We experimentally demonstrate the feasibility of the proposed method on a robot arm, and implement the method on a microcontroller. We verify the calibration results of the proposed method by comparing with a traditional turntable approach, and the experiment indicates that the results of these two methods are comparable. By comparing the calibrated low-cost gyroscope reading with the reading from a high-precision gyroscope, we can conclude that our method significantly increases the gyroscope's accuracy.
Wark, PAB, MacIntyre, CR, Bell, S, Oliver, B & Marks, GB 2021, 'We are not doing enough to prevent the spread of COVID‐19 and other respiratory viruses in Australian hospitals', Medical Journal of Australia, vol. 215, no. 4, pp. 152-152.
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The health care community has been accused of not taking the nosocomial spread of respiratory virus infection to health care workers and patients seriously enough. The evidence from the coronavirus disease 2019 (COVID-19) pandemic has demonstrated that our current approach to controlling respiratory viruses is not sufficient. The overrepresentation of health care workers among those acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in workplace settings is a clear testament to this with an adjusted hazard ratio of 3.40 (95% CI, 3.37–3.43).1 This issue needs to be critically examined in light of the emerging evidence from the COVID-19 pandemic.
Weaver, R, O'Connor, M, Ngune, I, Smith, RC, Phillips, J & Halkett, G 2021, 'Perspectives of the sarcoma clinical nurse consultant role: A qualitative study', Collegian, vol. 28, no. 4, pp. 422-430.
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Weckmann, M, Bahmer, T, Sand, JM, Rank Rønnow, S, Pech, M, Vermeulen, C, Faiz, A, Leeming, DJ, Karsdal, MA, Lunding, L, Oliver, BGG, Wegmann, M, Ulrich-Merzenich, G, Juergens, UR, Duhn, J, Laumonnier, Y, Danov, O, Sewald, K, Zissler, U, Jonker, M, König, I, Hansen, G, von Mutius, E, Fuchs, O, Dittrich, A-M, Schaub, B, Happle, C, Rabe, KF, van de Berge, M, Burgess, JK & Kopp, MV 2021, 'COL4A3 is degraded in allergic asthma and degradation predicts response to anti-IgE therapy', European Respiratory Journal, vol. 58, no. 6, pp. 2003969-2003969.
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BackgroundAsthma is a heterogeneous syndrome substantiating the urgent requirement for endotype-specific biomarkers. Dysbalance of fibrosis and fibrolysis in asthmatic lung tissue leads to reduced levels of the inflammation-protective collagen 4 (COL4A3).ObjectiveTo delineate the degradation of COL4A3 in allergic airway inflammation and evaluate the resultant product as a biomarker for anti-IgE therapy response.MethodsThe serological COL4A3 degradation marker C4Ma3 (Nordic Bioscience, Denmark) and serum cytokines were measured in the ALLIANCE cohort (paediatric cases/controls: n=134/n=35; adult cases/controls: n=149/n=31). Exacerbation of allergic airway disease in mice was induced by sensitising to ovalbumin (OVA), challenge with OVA aerosol and instillation of poly(cytidylic-inosinic). Fulacimstat (chymase inhibitor; Bayer) was used to determine the role of mast cell chymase in COL4A3 degradation. Patients with cystic fibrosis (n=14) and cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA; n=9) as well as patients with severe allergic uncontrolled asthma (n=19) were tested for COL4A3 degradation. Omalizumab (anti-IgE) treatment was assessed using the Asthma Control Test.ResultsSerum levels of C4Ma3 were increased in asthma in adults and children alike and linked to a more severe, exacerbating allergic asthma phenotype. In an experimental asthma mouse model, C4Ma3 was dependent on mast cell chymase. Serum C4Ma3 was significantly elevated in cystic fibrosis plus ABPA and at baseline predicted the success of the anti-IgE therapy in allergic, uncontrolled asthmatics (diagnostic OR 31.5).ConclusionC4Ma3 levels depend on lung mast cell chymase and are i...
Woldhuis, RR, Heijink, IH, van den Berge, M, Timens, W, Oliver, BGG, de Vries, M & Brandsma, C-A 2021, 'COPD-derived fibroblasts secrete higher levels of senescence-associated secretory phenotype proteins', Thorax, vol. 76, no. 5, pp. 508-511.
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COPD-derived fibroblasts have increased cellular senescence. Senescent cell accumulation can induce tissue dysfunction by their senescence-associated secretory phenotype (SASP). We aimed to determine the SASP of senescent fibroblasts and COPD-derived lung fibroblasts, including severe, early-onset (SEO)-COPD. SASP protein secretion was measured after paraquat-induced senescence in lung fibroblasts using Olink Proteomics and compared between (SEO-)COPD-derived and control-derived fibroblasts. We identified 124 SASP proteins of senescent lung fibroblasts, of which 42 were secreted at higher levels by COPD-derived fibroblasts and 35 by SEO-COPD-derived fibroblasts compared with controls. Interestingly, the (SEO-)COPD-associated SASP included proteins involved in chronic inflammation, which may contribute to (SEO-)COPD pathogenesis.
Wong, WKM, Joglekar, MV, Saini, V, Jiang, G, Dong, CX, Chaitarvornkit, A, Maciag, GJ, Gerace, D, Farr, RJ, Satoor, SN, Sahu, S, Sharangdhar, T, Ahmed, AS, Chew, YV, Liuwantara, D, Heng, B, Lim, CK, Hunter, J, Januszewski, AS, Sørensen, AE, Akil, ASA, Gamble, JR, Loudovaris, T, Kay, TW, Thomas, HE, O'Connell, PJ, Guillemin, GJ, Martin, D, Simpson, AM, Hawthorne, WJ, Dalgaard, LT, Ma, RCW & Hardikar, AA 2021, 'Machine learning workflows identify a microRNA signature of insulin transcription in human tissues', iScience, vol. 24, no. 4, pp. 102379-102379.
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Wood, MP, Jones, CI, Lippy, A, Oliver, BG, Walund, B, Fancher, KA, Fisher, BS, Wright, PJ, Fuller, JT, Murapa, P, Habib, J, Mavigner, M, Chahroudi, A, Sather, DN, Fuller, DH & Sodora, DL 2021, 'Rapid progression is associated with lymphoid follicle dysfunction in SIV-infected infant rhesus macaques', PLOS Pathogens, vol. 17, no. 5, pp. e1009575-e1009575.
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HIV-infected infants are at an increased risk of progressing rapidly to AIDS in the first weeks of life. Here, we evaluated immunological and virological parameters in 25 SIV-infected infant rhesus macaques to understand the factors influencing a rapid disease outcome. Infant macaques were infected with SIVmac251 and monitored for 10 to 17 weeks post-infection. SIV-infected infants were divided into either typical (TypP) or rapid (RP) progressor groups based on levels of plasma anti-SIV antibody and viral load, with RP infants having low SIV-specific antibodies and high viral loads. Following SIV infection, 11 out of 25 infant macaques exhibited an RP phenotype. Interestingly, TypP had lower levels of total CD4 T cells, similar reductions in CD4/CD8 ratios and elevated activation of CD8 T cells, as measured by the levels of HLA-DR, compared to RP. Differences between the two groups were identified in other immune cell populations, including a failure to expand activated memory (CD21-CD27+) B cells in peripheral blood in RP infant macaques, as well as reduced levels of germinal center (GC) B cells and T follicular helper (Tfh) cells in spleens (4- and 10-weeks post-SIV). Reduced B cell proliferation in splenic germinal GCs was associated with increased SIV+ cell density and follicular type 1 interferon (IFN)-induced immune activation. Further analyses determined that at 2-weeks post SIV infection TypP infants exhibited elevated levels of the GC-inducing chemokine CXCL13 in plasma, as well as significantly lower levels of viral envelope diversity compared to RP infants. Our findings provide evidence that early viral and immunologic events following SIV infection contributes to impairment of B cells, Tfh cells and germinal center formation, ultimately impeding the development of SIV-specific antibody responses in rapidly progressing infant macaques.
Wu, WW, Zhang, X, Li, M, Liu, Y, Chen, ZH, Xie, M, Zhao, SZ, Wang, G, Zhang, HP, Wang, T, Qin, L, Wang, L, Oliver, BG, Wan, HJ, Zhang, J, McDonald, VM, Marks, GB, Li, WM, Birring, SS, Wang, G & Gibson, PG 2021, 'Treatable Traits in Elderly Asthmatics from the Australasian Severe Asthma Network: A Prospective Cohort Study', The Journal of Allergy and Clinical Immunology: In Practice, vol. 9, no. 7, pp. 2770-2782.
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BACKGROUND: Data on treatable traits (TTs) in different populations are limited. OBJECTIVE: To assess TTs in elderly patients with asthma and compare them to younger patients, to evaluate the association of TTs with future exacerbations, and to develop an exacerbation prediction model. METHODS: We consecutively recruited 521 participants at West China Hospital, Sichuan University based on the Australasian Severe Asthma Network, classified as elderly (n = 62) and nonelderly (n = 459). Participants underwent a multidimensional assessment to characterize the TTs and were then followed up for 12 months. TTs and their relationship with future exacerbations were described. Based on the TTs and asthma control levels, an exacerbation prediction model was developed, and the overall performance was externally validated in an independent cohort. RESULTS: A total of 38 TTs were assessed. Elderly patients with asthma had more chronic metabolic diseases, fixed airflow limitation, emphysema, and neutrophilic inflammation, whereas nonelderly patients with asthma exhibited more allergic characteristics and psychiatric diseases. Nine traits were associated with increased future exacerbations, of which exacerbation prone, upper respiratory infection-induced asthma attack, cardiovascular disease, diabetes, and depression were the strongest. A model including exacerbation prone, psychiatric disease, cardiovascular disease, upper respiratory infection-induced asthma attack, noneosinophilic inflammation, cachexia, food allergy, and asthma control was developed to predict exacerbation risk and showed good performance. CONCLUSIONS: TTs can be systematically assessed in elderly patients with asthma, some of which are associated with future exacerbations, proving their clinical utility of evaluating them. A model based on TTs can be used to predict exacerbation risk in people with asthma.
Xiao, L, Somers, K, Murray, J, Pandher, R, Karsa, M, Ronca, E, Bongers, A, Terry, R, Ehteda, A, Gamble, LD, Issaeva, N, Leonova, KI, O'Connor, A, Mayoh, C, Venkat, P, Quek, H, Brand, J, Kusuma, FK, Pettitt, JA, Mosmann, E, Kearns, A, Eden, G, Alfred, S, Allan, S, Zhai, L, Kamili, A, Gifford, AJ, Carter, DR, Henderson, MJ, Fletcher, JI, Marshall, G, Johnstone, RW, Cesare, AJ, Ziegler, DS, Gudkov, AV, Gurova, KV, Norris, MD & Haber, M 2021, 'Dual Targeting of Chromatin Stability By The Curaxin CBL0137 and Histone Deacetylase Inhibitor Panobinostat Shows Significant Preclinical Efficacy in Neuroblastoma', Clinical Cancer Research, vol. 27, no. 15, pp. 4338-4352.
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Abstract Purpose: We investigated whether targeting chromatin stability through a combination of the curaxin CBL0137 with the histone deacetylase (HDAC) inhibitor, panobinostat, constitutes an effective multimodal treatment for high-risk neuroblastoma. Experimental Design: The effects of the drug combination on cancer growth were examined in vitro and in animal models of MYCN-amplified neuroblastoma. The molecular mechanisms of action were analyzed by multiple techniques including whole transcriptome profiling, immune deconvolution analysis, immunofluorescence, flow cytometry, pulsed-field gel electrophoresis, assays to assess cell growth and apoptosis, and a range of cell-based reporter systems to examine histone eviction, heterochromatin transcription, and chromatin compaction. Results: The combination of CBL0137 and panobinostat enhanced nucleosome destabilization, induced an IFN response, inhibited DNA damage repair, and synergistically suppressed cancer cell growth. Similar synergistic effects were observed when combining CBL0137 with other HDAC inhibitors. The CBL0137/panobinostat combination significantly delayed cancer progression in xenograft models of poor outcome high-risk neuroblastoma. Complete tumor regression was achieved in the transgenic Th-MYCN neuroblastoma model which was accompanied by induction of a type I IFN and immune response. Tumor transplantation experiments further confirmed that the presence of a competent adaptive immune system component allowed the exploitation of the full potential of the drug combination. ...
Xie, C, Yang, Q, Huang, Y, Su, S, Xu, T & Song, R 2021, 'A Hybrid Arm-Hand Rehabilitation Robot With EMG-Based Admittance Controller', IEEE Transactions on Biomedical Circuits and Systems, vol. 15, no. 6, pp. 1332-1342.
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Xie, H, Zheng, J, Chai, R & Nguyen, HT 2021, 'Robust tracking control of a differential drive wheeled mobile robot using fast nonsingular terminal sliding mode', Computers & Electrical Engineering, vol. 96, pp. 107488-107488.
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Differential drive wheeled mobile robots (DDWMRs) have been widely used in various applications due to their maneuverability and energy-saving characteristics. Tracking control of such mechanical systems with nonholonomic constraints in the presence of uncertainties and disturbances has attracted much attention. In this paper, a robust control scheme is developed for trajectory tracking control of a DDWMR in the presence of parametric uncertainties and disturbances. To fulfill the controller design, an inner–outer loop control structure is adopted for the DDWMR. For the inner-loop controller, a fast nonsingular terminal sliding mode (FNTSM) control law is applied for robust disturbance rejection in a finite time. Based on the kinematic model of the DDWMR, the outer-loop controller is designed for accurate trajectory tracking control. Finally, experiments are carried out to validate that the proposed control scheme has more robust tracking accuracy and faster response than an existing robust method.
Xu, X, Inglis, SC & Parker, D 2021, 'Sex differences in dietary consumption and its association with frailty among middle-aged and older Australians: a 10-year longitudinal survey', BMC Geriatrics, vol. 21, no. 1.
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Abstract Background Nutritional status has been considered as a key factor in preventing the development of the frailty syndrome. However, sex-specific dietary consumption transition over time and how it impacts of frailty status are unclear. Method We assessed 113,039 adults (aged 50 years and over) from the 45 and Up Study who had completed both baseline (2006–2009) and follow-up (2012–2015) surveys. Dietary consumption was assessed by a short food frequency questionnaire. Frailty was identified by the FRAIL scale. Multinomial regression models were used to examine the association between a long-term dietary consumption and frailty, stratified by sex. Results Of a total of 113,039 participants, females had a higher percentage of pre-frailty and frailty than males (pre-frailty: 35.5% for female and 30.1% for male; frailty: 4.86% for female and 3.56% for male). As age increased, males had significant decreases in overall dietary risk scores, while females had significant increases in overall dietary risk scores. Males and females with a long-term consumption of adequate fruits, high grains or had a variety of foods were related to a low risk of frailty. Females with a long-term consumption of adequate vegetables or high lean meats and poultry were related to a low risk of frailty. Females with an unhealthy diet at both surveys [Relative Risk Ratio (RRR) = 1.32, 95% CI: 1.18; 1.49], and those with unhealthy diet at either surveys (RRR = 1.28, 95% CI: 1.12; 1.47, RRR = 1.19, 95% CI: 1.04; 1.37) had a higher risk of frailty compared to those had a long-term healthy diet. No association were found between overall dietary risk and frailty for m...
Yin, L, Au, WY, Yu, CC, Kwon, T, Lai, Z, Shang, M, Warkiani, ME, Rosche, R, Lim, CT & Han, J 2021, 'Miniature auto‐perfusion bioreactor system with spiral microfluidic cell retention device', Biotechnology and Bioengineering, vol. 118, no. 5, pp. 1951-1961.
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AbstractMedium perfusion is critical in maintaining high cell concentration in cultures. The conventional membrane filtration method for medium exchange has been challenged by the fouling and clogging of the membrane filters in long‐term cultures. In this study, we present a miniature auto‐perfusion system that can be operated inside a common‐size laboratory incubator. The system is equipped with a spiral microfluidic chip for cell retention to replace conventional membrane filters, which fundamentally overcomes the clogging and fouling problem. We showed that the system supported continuous perfusion culture of Chinese hamster ovary (CHO) cells in suspension up to 14 days without cell retention chip replacement. Compared to daily manual medium change, 25% higher CHO cell concentration can be maintained at an average auto‐perfusion rate of 196 ml/day in spinner flask at 70 ml working volume (2.8 VVD). The auto‐perfusion system also resulted in better cell quality at high concentrations, in terms of higher viability, more uniform and regular morphology, and fewer aggregates. We also demonstrated the potential application of the system for culturing mesenchymal stem cells on microcarriers. This miniature auto‐perfusion system provides an excellent solution to maintain cell‐favorable conditions and high cell concentration in small‐scale cultures for research and clinical uses.
Yu, H, Ye, L, Guo, Y & Su, S 2021, 'An Effective In-Field Calibration Method for Triaxial Magnetometers Based on Local Magnetic Inclination', IEEE Transactions on Instrumentation and Measurement, vol. 70, pp. 1-9.
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Yuan, YL, Zhang, X, Liu, L, Wang, G, Chen-Yu Hsu, A, Huang, D, Wang, G & Oliver, BG 2021, 'Total IgE Variability Is Associated with Future Asthma Exacerbations: A 1-Year Prospective Cohort Study', The Journal of Allergy and Clinical Immunology: In Practice, vol. 9, no. 7, pp. 2812-2824.
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BACKGROUND: Few prospective studies have investigated the relationship between IgE variability and risk for asthma exacerbations (AEs). OBJECTIVE: To explore the relationship between IgE variability and AEs. METHODS: Recruited patients with stable asthma underwent two serum total IgE tests within a month (at screening [baseline IgE] and at 1 month) to obtain the coefficient of variation (CV) of base 10 log-transformed IgE. Patients with IgE CV were divided into IgE CV-high and IgE CV-low cohorts based on the CV median and were observed within 12 months, during which the association between IgE variability and AEs was explored using a negative binomial regression model. RESULTS: The IgE CV levels obtained from 340 patients classified patients into two groups (n = 170 for the IgE CV-high and IgE CV-low groups, respectively) based on the serum total IgE CV median of 2.12% (quartiles 1 and 3: 0.98% and 3.91%, respectively). The IgE CV-high patients exhibited worse asthma control and lung function and more marked airway inflammation, and received more intensive medication use compared with IgE CV-low patients. The IgE CV-high patients exhibited increased rates of moderate-to-severe (adjusted rate ratio = 2.88; 95% confidence interval, 1.65-5.03; P < .001) and severe (adjusted rate ratio = 2.16; 95% confidence interval, 1.08-4.32; P = .029) AEs during the follow-up year compared with IgE CV-low patients. Furthermore, sputum IL-6 partially mediated the associations between IgE CV with moderate-to-severe and severe AEs. CONCLUSIONS: Variability in total serum IgE levels is an easily obtained and practical measure for predicting AEs. Future studies are needed to investigate whether IgE variability can be used to guide precision medicine in asthma.
Zakarya, R, Chan, YL, Rutting, S, Reddy, K, Bozier, J, Woldhuis, RR, Xenaki, D, Van Ly, D, Chen, H, Brandsma, C-A, Adcock, IM & Oliver, BG 2021, 'BET proteins are associated with the induction of small airway fibrosis in COPD', Thorax, vol. 76, no. 7, pp. 647-655.
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RationaleIn COPD, small airway fibrosis occurs due to increased extracellular matrix (ECM) deposition in and around the airway smooth muscle (ASM) layer. Studies of immune cells and peripheral lung tissue have shown that epigenetic changes occur in COPD but it is unknown whether airway mesenchymal cells are reprogrammed.ObjectivesDetermine if COPD ASM cells have a unique epigenetic response to profibrotic cytokine transforming growth factor β1 (TGF-β1).MethodsPrimary human ASM cells from COPD and non-COPD smoking patients were stimulated with TGF-β1. Gene array analysis performed to identify differences in ECM expression. Airway accumulation of collagen 15α1 and tenascin-C proteins was assessed. Aforementioned ASM cells were stimulated with TGF-β1 ± epigenetic inhibitors with qPCR quantification of COL15A1 and TNC. Global histone acetyltransferase (HAT) and histone deacetylase (HDAC) activity were assessed. chromatin immunoprecipitation (ChIP)-qPCR for histone H3 and H4 acetylation at COL15A1 and TNC promoters was carried out. Effects of bromoterminal and extraterminal domain (BET) inhibitor JQ1(+) on expression and acetylation of ECM target genes were assessed.Measurements and main resultsCOPD ASM show significantly higher COL15A1 and TNC expression in vitro and the same trend for higher levels of collagen 15α1 and tenascin-c deposited in COPD airways in vivo. Epigenetic screening indicated differential response to HDAC inhibition. ChIP-qPCR revealed histone H4 acetylation at COL15A1 and TNC promoters in COPD A...
Zeng, Y, Huang, T, Wang, N, Xu, Y, Sun, C, Huang, M, Chen, C, Oliver, BG, Yi, C & Chen, H 2021, 'L-Leucine Improves Metabolic Disorders in Mice With in-utero Cigarette Smoke Exposure', Frontiers in Physiology, vol. 12, p. 700246.
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Objectives: Maternal cigarette smoke exposure (SE) causes intrauterine undernutrition, resulting in increased risk for metabolic disorders and type 2 diabetes in the offspring without sex differences. L-leucine supplementation has been shown to reduce body weight and improve glucose metabolism in both obese animals and humans. In this study, we aimed to determine whether postnatal L-leucine supplementation in female offspring can ameliorate the detrimental impact of maternal SE.Methods: Female Balb/c mice (6-week) were exposed to cigarette smoke (SE, 2 cigarettes/day) prior to mating for 5 weeks until the pups weaned. Sham dams were exposed to air during the same period. Half of the female offspring from the SE and SHAM dams were supplied with L-leucine via drinking water (1.5% w/w) after weaning (21-day) for 10 weeks and sacrificed at 13 weeks (adulthood).Results: Maternal SE during pregnancy resulted in smaller body weight and glucose intolerance in the offspring. L-leucine supplement in Sham offspring reduced body weight, fat mass, and fasting blood glucose levels compared with their untreated littermates; however somatic growth was not changed. L-leucine supplement in SE offspring improved glucose tolerance and reduced fat mass compared with untreated littermates.Conclusions: Postnatal L-leucine supplement could reduce fat accumulation and ameliorate glucose metabolic disorder caused by maternal SE. The application of leucine may provide a potential strategy for reducing metabolic disorders in offspring from mothers who continued to smoke during pregnancy.
Zhand, S, Xiao, K, Razavi Bazaz, S, Zhu, Y, Bordhan, P, Jin, D & Warkiani, ME 2021, 'Improving capture efficiency of human cancer cell derived exosomes with nanostructured metal organic framework functionalized beads', Applied Materials Today, vol. 23, pp. 100994-100994.
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Extracellular vesicles (EVs) have emerged as an invaluable tool for analyzing the physiological processes and an alternative source of disease diagnostic and prognostic biomarkers in liquid biopsies. Exosomes are a subset of EVs offer a window into altered cellular or tissue states, and their detection potentially offers a multicomponent early-stage diagnostic readout. Immunocapture and flow cytometry analysis of exosomes using micron-sized beads has been reported to be a reproducible technique for analysis of exosome surface markers. Nevertheless, the capture capacity remains poor due to limited available surface area. In this study, we have proposed a nanocoating strategy using metal-organic framework (MOF) materials, in particular, Zeolitic Imidazolate Framework-8 (ZIF-8), for highly efficient capturing of low concentration of exosomes from minimally processed samples. In this method, a ZIF-8 thin film was formed on polydopamine-polyethyleneimine (PDA-PEI) coated polystyrene microbeads to improve antibody immobilization due to the larger surface area provided by the MOF microstructures. This novel coating enabled us to detect as little as 50 exosomes per 10 µm polystyrene bead functionalized with ZIF-8/PDA-PEI, which is 180 times higher than the previously reported methods using naked microbeads. This coating requires a lower concentration of antibody to capture exosomes on the surface of microbeads compared to the standard protocols. More importantly, the higher concentration of exosomes on each bead surface provides the opportunity (i.e., higher signal intensity) to sort the beads using fluorescence-activated cell sorting, facilitating molecular analysis of post fractionation exosomes. Additionally, the exosomes can easily be detached from the coated microbeads using EDTA, limiting the usage of harsh chemicals. The procedure described here can be easily reproduced and employed regardless of the biological sample used to obtain exosomes.
Zhang, M, Li, H, Pan, S, Chang, X, Zhou, C, Ge, Z & Su, S 2021, 'One-Shot Neural Architecture Search: Maximising Diversity to Overcome Catastrophic Forgetting', IEEE Transactions on Pattern Analysis and Machine Intelligence, vol. 43, no. 9, pp. 2921-2935.
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One-shot neural architecture search (NAS) has recently become mainstream in the NAS community because it significantly improves computational efficiency through weight sharing. However, the supernet training paradigm in one-shot NAS introduces catastrophic forgetting. To overcome this problem of catastrophic forgetting, we formulate supernet training for one-shot NAS as a constrained continual learning optimization problem such that learning the current architecture does not degrade the validation accuracy of previous architectures. The key to solving this constrained optimization problem is a novelty search based architecture selection (NSAS) loss function that regularizes the supernet training by using a greedy novelty search method to find the most representative subset. We applied the NSAS loss function to two one-shot NAS baselines and extensively tested them on both a common search space and a NAS benchmark dataset. We further derive three variants based on the NSAS loss function, the NSAS with depth constrain (NSAS-C) to improve the transferability, and NSAS-G and NSAS-LG to handle the situation with a limited number of constraints. The experiments on the common NAS search space demonstrate that NSAS and it variants improve the predictive ability of supernet training in one-shot NAS baselines.
Zhang, M, Li, H, Pan, S, Lyu, J, Ling, SSH & Su, SW 2021, 'Convolutional Neural Networks-Based Lung Nodule Classification: A Surrogate-Assisted Evolutionary Algorithm for Hyperparameter Optimization.', IEEE Trans. Evol. Comput., vol. 25, no. 5, pp. 869-882.
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This article investigates deep neural networks (DNNs)-based lung nodule classification with hyperparameter optimization. Hyperparameter optimization in DNNs is a computationally expensive problem, and a surrogate-Assisted evolutionary algorithm has been recently introduced to automatically search for optimal hyperparameter configurations of DNNs, by applying computationally efficient surrogate models to approximate the validation error function of hyperparameter configurations. Different from existing surrogate models adopting stationary covariance functions (kernels) to measure the difference between hyperparameter points, this article proposes a nonstationary kernel that allows the surrogate model to adapt to functions whose smoothness varies with the spatial location of inputs. A multilevel convolutional neural network (ML-CNN) is built for lung nodule classification, and the hyperparameter configuration is optimized by the proposed nonstationary kernel-based Gaussian surrogate model. Our algorithm searches with a surrogate for optimal setting via a hyperparameter importance-based evolutionary strategy, and the experiments demonstrate our algorithm outperforms manual tuning and several well-established hyperparameter optimization methods, including random search, grid search, the tree-structured parzen estimator (TPE) approach, Gaussian processes (GP) with stationary kernels, and the recently proposed hyperparameter optimization via RBF and dynamic (HORD) coordinate search.
Zhang, X, Liu, Y, Yu, Z, Blumenstein, M, Hutvagner, G & Li, J 2021, 'Instance-based error correction for short reads of disease-associated genes', BMC Bioinformatics, vol. 22, no. S6, pp. 1-17.
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Abstract Background Genomic reads from sequencing platforms contain random errors. Global correction algorithms have been developed, aiming to rectify all possible errors in the reads using generic genome-wide patterns. However, the non-uniform sequencing depths hinder the global approach to conduct effective error removal. As some genes may get under-corrected or over-corrected by the global approach, we conduct instance-based error correction for short reads of disease-associated genes or pathways. The paramount requirement is to ensure the relevant reads, instead of the whole genome, are error-free to provide significant benefits for single-nucleotide polymorphism (SNP) or variant calling studies on the specific genes. Results To rectify possible errors in the short reads of disease-associated genes, our novel idea is to exploit local sequence features and statistics directly related to these genes. Extensive experiments are conducted in comparison with state-of-the-art methods on both simulated and real datasets of lung cancer associated genes (including single-end and paired-end reads). The results demonstrated the superiority of our method with the best performance on precision, recall and gain rate, as well as on sequence assembly results (e.g., N50, the length of contig and contig quality). Conclusion Instance-based strategy makes it possible to explore fine-grained patterns focusing on specific genes, providing high precision error correction and convincing gene sequence assembly. SNP case studies show that errors occurring at some traditional SNP areas can be accurately corrected, providing high precision and sensitivity for inve...
Zhang, X, Ping, P, Hutvagner, G, Blumenstein, M & Li, J 2021, 'Aberration-corrected ultrafine analysis of miRNA reads at single-base resolution: a k-mer lattice approach', Nucleic Acids Research, vol. 49, no. 18, pp. e106-e106.
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Abstract Raw sequencing reads of miRNAs contain machine-made substitution errors, or even insertions and deletions (indels). Although the error rate can be low at 0.1%, precise rectification of these errors is critically important because isoform variation analysis at single-base resolution such as novel isomiR discovery, editing events understanding, differential expression analysis, or tissue-specific isoform identification is very sensitive to base positions and copy counts of the reads. Existing error correction methods do not work for miRNA sequencing data attributed to miRNAs’ length and per-read-coverage properties distinct from DNA or mRNA sequencing reads. We present a novel lattice structure combining kmers, (k – 1)mers and (k + 1)mers to address this problem. The method is particularly effective for the correction of indel errors. Extensive tests on datasets having known ground truth of errors demonstrate that the method is able to remove almost all of the errors, without introducing any new error, to improve the data quality from every-50-reads containing one error to every-1300-reads containing one error. Studies on experimental miRNA sequencing datasets show that the errors are often rectified at the 5′ ends and the seed regions of the reads, and that there are remarkable changes after the correction in miRNA isoform abundance, volume of singleton reads, overall entropy, isomiR families, tissue-specific miRNAs, and rare-miRNA quantities.
Zhang, X, Zheng, Y, Zhao, Z, Liu, Y, Blumenstein, M & Li, J 2021, 'Deep learning detection of anomalous patterns from bus trajectories for traffic insight analysis', Knowledge-Based Systems, vol. 217, pp. 106833-106833.
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Existing data-driven methods for traffic anomaly detection are modeled on taxi trajectory datasets. The concern is that the data may contain much inaccuracy about the actual traffic situations, because taxi drivers often choose optimal routes to evade from the congestions caused by traffic anomalies. We use bus trajectory data in this work. Bus trajectories can capture real traffic conditions in the road networks without drivers’ preference, which are more objective and appropriate for accurately detecting anomalous patterns for a broad range of insight analyses on traffics. We proposed a deep learning-based feature visualization method to map 3-dimensional features into a red–green–blue (RGB) color space. A color trajectory (CT) is then derived by encoding a trajectory with the RGB colors. With the spatial and temporal properties extracted from the CT, spatio-temporal outliers are detected by a novel offline detection method. We then conduct GIS map fusion to obtain insights for better understanding the traffic anomaly locations, and more importantly the influences on the road affected by the corresponding anomalies. Extended from the offline detection, an online detection method is developed for real-time detection of anomalous patterns. Our proposed methods were tested on 3 real-world bus trajectory datasets to demonstrate the performance of high accuracies, high detection rates and relatively low false alarm rates.
Zhang, Y, Wang, Z, Cao, Y, Zhang, L, Wang, G, Dong, F, Deng, R, Guo, B, Zeng, L, Wang, P, Dai, R, Ran, Y, Lyu, W, Miao, P & Su, S 2021, 'The effect of consecutive ambient air pollution on the hospital admission from chronic obstructive pulmonary disease in the Chengdu region, China', Air Quality, Atmosphere & Health, vol. 14, no. 7, pp. 1049-1061.
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Hospitalisation risks for chronic obstructive pulmonary disease (COPD) have been attributed to ambient air pollution worldwide. However, a rise in COPD hospitalisations may indicate a considerable increase in fatality rate in public health. The current study focuses on the association between consecutive ambient air pollution (CAAP) and COPD hospitalisation to offer predictable early guidance towards estimates of COPD hospital admissions in the event of consecutive exposure to air pollution. Big data analytics were collected from 3-year time series recordings (from 2015 to 2017) of both air data and COPD hospitalisation data in the Chengdu region in China. Based on the combined effects of CAAP and unit increase in air pollutant concentrations, a quasi-Poisson regression model was established, which revealed the association between CAAP and estimated COPD admissions. The results show the dynamics and outbreaks in the variations in COPD admissions in response to CAAP. Cross-validation and mean squared error (MSE) are applied to validate the goodness of fit. In both short-term and long-term air pollution exposures, Z test outcomes show that the COPD hospitalisation risk is greater for men than for women; similarly, the occurrence of COPD hospital admissions in the group of elderly people (> 65 years old) is significantly larger than that in lower age groups. The time lag between the air quality and COPD hospitalisation is also investigated, and a peak of COPD hospitalisation risk is found to lag 2 days for air quality index (AQI) and PM10, and 1 day for PM2.5. The big data-based predictive paradigm would be a measure for the early detection of a public health event in post-COVID-19. The study findings can also provide guidance for COPD admissions in the event of consecutive exposure to air pollution in the Chengdu region.
Zhang, Y, Yang, Q, Zhang, L, Ran, Y, Wang, G, Celler, B, Su, S, Xu, P & Yao, D 2021, 'Noise-assisted multivariate empirical mode decomposition based causal decomposition for brain-physiological network in bivariate and multiscale time series', Journal of Neural Engineering, vol. 18, no. 4, pp. 046018-046018.
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Abstract Objective. Noise-assisted multivariate empirical mode decomposition (NA-MEMD) based causal decomposition depicts a cause and effect relationship that is not based on the term of prediction, but rather on the phase dependence of time series. Here, we present the NA-MEMD based causal decomposition approach according to the covariation and power views traced to Hume and Kant: a priori cause-effect interaction is first acquired, and the presence of a candidate cause and of the effect is then computed from the sensory input somehow. Approach. Based on the definition of NA-MEMD based causal decomposition, we show such causal relation is a phase relation where the candidate causes are not merely followed by effects, but rather produce effects. Main results. The predominant methods used in neuroscience (Granger causality, empirical mode decomposition-based causal decomposition) are validated, showing the applicability of NA-MEMD based causal decomposition, particular to brain physiological processes in bivariate and multiscale time series. Significance. We point to the potential use in the causality inference analysis in a complex dynamic process.
Zhao, Z, Wang, Z, Tavakoli, J, Shan, G, Zhang, J, Peng, C, Xiong, Y, Zhang, X, Cheung, TS, Tang, Y, Huang, B, Yu, Z, Lam, JWY & Tang, BZ 2021, 'Revisiting an ancient inorganic aggregation‐induced emission system: An enlightenment to clusteroluminescence', Aggregate, vol. 2, no. 2.
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AbstractOrganic and inorganic clusteroluminescence have attracted great attention while the underlying mechanisms is still not well understood. Here, we employed a series of ancient inorganic complexes platinocyanides with aggregation‐induced emission property to elucidate the mechanism of clusteroluminescence including how does the chromophore form and how does the solid structures influence the luminescence behaviors. The results indicate that the isolated platinocyanide cannot work as a chromophore to emit visible light, while their clusterization at aggregate state can trigger the d‐orbitals coupling of the platinum atoms to facilitate the electron exchange and delocalization to form a new chromophore to emit visible light. Furthermore, the counter ions and H2O ligands help to rigidify the three‐dimensional network structure of the platinocyanides to suppress the excited state nonradiative decay, resulting in the high quantum yield of up to 96%. This work fundamentally helps understanding both the organic and inorganic clusteroluminescence phenomenon.
Zheng, D, Zhang, H, Zhang, JA & Su, SW 2021, 'Stability of Switched Systems with Unstable Subsystems: A Sequence-Based Average Dwell Time Approach', Circuits, Systems, and Signal Processing, vol. 40, no. 11, pp. 5328-5350.
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This paper proposes a new sequence-based approach to resolve the stability problems found in switched systems with unstable subsystems. In existing approaches, the sequence information of switching subsystems is seldom exploited. By exploiting the sequence information, threshold values can be less restrictive and more appropriate for the situation. We study two cases in this paper: (a) all subsystems are unstable, and (b) part of the subsystems are unstable. Both continuous-time and discrete-time systems are studied, and a numerical example is given to show the advantage of our approach.
Zhou, M, Zhang, H, Li, F, Yu, Z, Yuan, C, Oliver, B & Li, J 2021, 'Pulmonary Daoyin as a traditional Chinese medicine rehabilitation programme for patients with IPF: A randomized controlled trial', Respirology, vol. 26, no. 4, pp. 360-369.
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ABSTRACTBackground and objectiveIPF is a chronic progressive lung disease in which PR provides benefit for patients. PD, a TCM PR programme, has known effectiveness in COPD, but its utility in IPF is unknown. We investigated its effectiveness and safety in patients with IPF.MethodsA 6‐month randomized controlled trial (RCT) was conducted in three Chinese clinics. Ninety‐six participants diagnosed with IPF were randomly assigned to one of the three groups: the PD group received a PD programme two times a day, 5 days/week for 2 months, and the exercise group exercised via a stationary cycle ergometer, 30 min/day, 5 days/week for 2 months. Volunteers in the control group were advised to maintain their usual activities. Primary outcomes were changes from baseline in the 6MWD and HRQoL score on the SGRQ‐I at 1 and 2 months (at the end of the intervention) and at 6 months (4 months after the intervention). Secondary outcomes measures included FVC, DLCO (% predicted) and the changes in mMRC.ResultsThe 6MWD was increased in the PD group compared to exercise and control groups. 6MWD increased by 60.44 m in the PD group, 32.16 m in the exercise group and 12.42 m in controls after the 2 months of rehabilitation programme. The between‐group differences in the change from baseline were 28.78 m (95% CI: 0.54 to 56.01; P = 0.044) and 48.02 m (95% CI: 23.04 to 73.00; P < 0.001) at 2 months, and 25.61 m (95% CI: −0.67 to 51.89; P = 0.058) and 50.93 m (95% CI: 25.47 to 76.40; P < 0.001) at 6 months, respectively, including a difference exceeding the MCID. There was no significant change in the SGRQ‐I score, the mMRC dyspnoea score, FVC and DL
Zhu, WJ, Liu, Y, Wang, G, Deng, K, Liu, L, Wang, J, Oliver, BG, Wang, T, Kang, DY, Wang, L, Li, WM & Wang, G 2021, 'Interaction effects of asthma and rhinitis control on work productivity and activity impairment: A cross-sectional study', Allergy and Asthma Proceedings, vol. 42, no. 5, pp. 409-416.
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Background: Symptomatic asthma and rhinitis negatively impact patients' work productivity and activity. However, little is known about the potential interaction effect of both asthma and rhinitis control on work productivity and activity impairment. Objective: This study aimed to explore whether there are interaction effects of asthma and rhinitis control on work productivity and activity impairment in patients with asthma and with rhinitis. Methods: A total of 206 adult patients were prospectively recruited and were divided into four groups: both poorly controlled (BPC) n = 53), poorly controlled asthma (PCA) with controlled rhinitis (CR) (n = 38), well controlled asthma with uncontrolled rhinitis (n = 43), and both well controlled (BWC) (n = 72) based on the symptom control status of asthma and rhinitis. Work productivity loss and activity impairment, asthma control, and rhinitis control were assessed by using work productivity and activity impairment questionnaire: general health, the asthma control test, and the rhinitis control assessment test, respectively. General linear regression models were used to study the contribution of asthma control, rhinitis control, and the interaction effect on work productivity and activity impairment. Results: Work productivity loss was most frequently reported in patients in the BPC group. Compared with the patients in the BWC group, the patients in the PCA-CR group had significantly higher activity impairment and worse asthma-related quality of life (both p < 0.001). There were significant interaction effects of asthma and rhinitis control, which accounted for the increase in presenteeism, work productivity loss, and activity impairment (all p < 0.001). Although differences in absenteeism were not significant among the groups, there was a significant interaction effect of control levels accounted for ...
Zhuang, Y, Leng, Y, Zhou, J, Song, R, Li, L & Su, SW 2021, 'Voluntary Control of an Ankle Joint Exoskeleton by Able-Bodied Individuals and Stroke Survivors Using EMG-Based Admittance Control Scheme', IEEE Transactions on Biomedical Engineering, vol. 68, no. 2, pp. 695-705.
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Control schemes based on electromyography (EMG) have demonstrated their superiority in human-robot cooperation due to the fact that motion intention can be well estimated by EMG signals. However, there are several limitations due to the noisy nature of EMG signals and the inaccuracy of EMG-force/torque estimation, which might deteriorate the stability of human-robot cooperation movement. To improve the movement stability, an EMG-based admittance control scheme (EACS) was proposed, comprised of an EMG-driven musculoskeletal model (EDMM), an admittance filter and an inner position controller. To investigate the performance of EACS, a series of sinusoidal tracking tasks were conducted with 12 healthy participants and 4 stroke survivors in an ankle exoskeleton in comparison with the EMG-based open-loop control scheme (EOCS). The experimental results indicated that both EACS and EOCS could improve stroke survivors' ankle range of motion (ROM). The experimental results of both healthy participants and stroke survivors showed that the assistance torque, tracking error and jerk values of EACS were lower than those of EOCS. The interaction torque of EACS decreased towards the increasing assistance ratio while that of EOCS increased. Moreover, the EMG levels of tibialis anterior (TA) decreased towards the increasing assistance ratio but were higher than those of EOCS. EACS was effective in improving movements stability, and had the potential to be applied in robot-assisted rehabilitation training to address the foot-drop problem.
