Publications

Javad, T, Yu, D & Youhong, T 2017, 'Biomedical polymer hybrid composites' in Hybrid Polymer Composite Materials, Elsevier, pp. 135-162.
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Khoo, BL, Chaudhuri, PK, Lim, CT & Warkiani, ME 2017, 'Advancing Techniques and Insights in Circulating Tumor Cell (CTC) Research' in Cancer Drug Discovery and Development, Springer International Publishing, pp. 71-94.
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Cancer is a major cause of mortality worldwide, with a disease burden estimated to grow over the coming decades. Circulating tumor cells (CTCs) are rare cancer cells released from the primary or metastatic tumors and transported though the peripheral circulatory system to their specific secondary locations. The presence of CTCs in the a cancer patient’s blood has been used as a prognostic biomarker, with lower CTC count correlating with greater overall survival [1]. In spite of its clinical potential, the isolation and detection of CTCs has been a challenging task due to its rare presence amongst other blood cells (as low as 1-10 CTCs per billions of blood cells) and variability in terms of both morphological and biochemical markers. Recent developments of microfluidics technology have paved the way for better isolation and characterization of CTCs due to several advantages such as lower sample volume, higher sensitivity and throughput and lesser production cost [2, 3]. In this chapter, various CTC isolation devices are classified under two major categories: microfluidics and conventional macro-scale devices, as illustrated in Fig. 1. We will be discussing both label-free methods and antibody-dependent methods for CTC isolation, and will provide discussion and future perspectives on the advantages and drawbacks of both these techniques on potential clinical applications. Advancement in these technologies for CTCs and associated components, such as exosomes, led to an unraveling of tumor variation, ranging histology, molecular, proteomic and functional heterogeneity, which will be discussed in the subsequent sections.

Mawad, D, Figtree, G & Gentile, C 2017, 'Current Technologies Based on the Knowledge of the Stem Cells Microenvironments' in Birbrair, A (ed), Advances in Experimental Medicine and Biology, Springer International Publishing, pp. 245-262.
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Pandya, HJ, Draz, MS, Warkiani, ME & Shafiee, H 2017, 'Diagnostic Devices with Microfluidics' in Piraino, F, Selimović, Š & Iniewski, K (eds), Diagnostic Devices with Microfluidics, CRC Press, pp. 145-161.
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Infectious diseases remain the primary public health challenge in many countries. Every year, infectious diseases account for more than 13 million deaths around the world, and for 30% of the total burden of disease. Developing countries are especially challenged with infectious diseases. According to world health organization (WHO), 50% of the total deaths in developing countries are attributed to various infections, including respiratory tract infections, diarrheal diseases, human immunodeficiency virus (HIV), tuberculosis, and malaria. In the healthcare system, a diagnostic cycle consists of several time-consuming steps besides sample transportation, pre-and postanalytical phases, result transmission, and batching practices augmenting the turnaround time from disease interpretation to results (Figure 7.1) [1-3]. The downside of experience-based empiric therapy management involves the choice of inappropriate antibiotherapy or late initiation of treatment often resulting in treatment failure [4-7].

Xie, F, Deng, W & Goldys, EM 2017, 'Compatibility of Metal‐Induced Fluorescence Enhancement with Applications in Analytical Chemistry and Biosensing' in Surface Plasmon Enhanced, Coupled and Controlled Fluorescence, Wiley, pp. 13-35.
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Ahadi, A, Sablok, G & Hutvagner, G 2017, 'miRTar2GO: a novel rule-based model learning method for cell line specific microRNA target prediction that integrates Ago2 CLIP-Seq and validated microRNA–target interaction data', Nucleic Acids Research, vol. 45, no. 6, pp. e42-e42.
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© 2016 The Author(s). MicroRNAs (miRNAs) are ∼19-22 nucleotides (nt) long regulatory RNAs that regulate gene expression by recognizing and binding to complementary sequences on mRNAs. The key step in revealing the function of a miRNA, is the identification of miRNA target genes. Recent biochemical advances including PAR-CLIP and HITS-CLIP allow for improved miRNA target predictions and are widely used to validate miRNA targets. Here, we present miRTar2GO, which is a model, trained on the common rules of miRNA-target interactions, Argonaute (Ago) CLIP-Seq data and experimentally validated miRNA target interactions. miRTar2GO is designed to predict miRNA target sites using more relaxed miRNA-target binding characteristics. More importantly, miRTar2GO allows for the prediction of celltype specific miRNA targets. We have evaluated miRTar2GO against other widely used miRNA target prediction algorithms and demonstrated that miRTar2GO produced significantly higher F1 and G scores. Target predictions, binding specifications, results of the pathway analysis and gene ontology enrichment of miRNA targets are freely available at http://www.mirtar2go.org.

Al Muderis, M, Lu, W & Li, JJ 2017, 'Osseointegrated Prosthetic Limb for the treatment of lower limb amputations', Der Unfallchirurg, vol. 120, no. 4, pp. 306-311.
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BACKGROUND: Osseointegration has emerged over the past two decades as a dramatically different approach for the treatment of lower limb amputations, which involves direct attachment of the prosthesis to the skeletal residuum. This approach can address many of the socket-interface issues associated with socket prostheses which represent the current standard of care for amputees. The Osseointegrated Prosthetic Limb (OPL) is an osseointegration implant with a new design and improved features compared to other available implant systems. OBJECTIVES: To report on the experience and outcomes of using the OPL for osseointegrated reconstruction of lower limb amputations. MATERIALS AND METHODS: This is a retrospective study of 22 patients who received the OPL implant between December 2013 and November 2014. Clinical outcomes were obtained pre- and post-operatively, with results reported at the 1‑year follow-up. Outcome measures included the Questionnaire for persons with a Trans-Femoral Amputation (Q-TFA), Short Form Health Survey 36 (SF-36), Six-Minute Walk Test (6MWT), and Timed Up and Go (TUG). Adverse events were also recorded. RESULTS: Compared to the mean pre-operative values obtained while patients were using socket prostheses or were wheelchair-bound, the mean post-operative values for all four validated outcome measures were significantly improved. There were 15 episodes of minor infections in 12 patients, all of which responded to antibiotics. Soft tissue refashioning was performed electively on 6 patients. No other adverse events were recorded. CONCLUSIONS: The results demonstrate that osseointegration surgery using the OPL is a relatively safe and effective procedure for the reconstruction and rehabilitation of lower limb amputees.

Al Muderis, M, Lu, W, Tetsworth, K, Bosley, B & Li, JJ 2017, 'Single-stage osseointegrated reconstruction and rehabilitation of lower limb amputees: the Osseointegration Group of Australia Accelerated Protocol-2 (OGAAP-2) for a prospective cohort study', BMJ Open, vol. 7, no. 3, pp. e013508-e013508.
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Introduction

Lower limb amputations have detrimental influences on the quality of life, function and body image of the affected patients. Following amputation, prolonged rehabilitation is required for patients to be fitted with traditional socket prostheses, and many patients experience symptomatic socket-residuum interface problems which lead to reduced prosthetic use and quality of life. Osseointegration has recently emerged as a novel approach for the reconstruction of amputated limbs, which overcomes many of the socket-related problems by directly attaching the prosthesis to the skeletal residuum. To date, the vast majority of osseointegration procedures worldwide have been performed in 2 stages, which require at least 4 months and up to 18 months for the completion of reconstruction and rehabilitation from the time of the initial surgery. The current prospective cohort study evaluates the safety and efficacy of a single-stage osseointegration procedure performed under the Osseointegration Group of Australia Accelerated Protocol-2 (OGAAP-2), which dramatically reduces the time of recovery to ∼3-6 weeks.

Methods and analysis

The inclusion criteria for osseointegrated reconstruction under the OGAAP-2 procedure are age over 18 years, unilateral transfemoral amputation and experiencing problems or difficulties in using socket prostheses. All patients receive osseointegrated implants which are press-fitted into the residual bone. Functional and quality-of-life outcome measures are recorded preoperatively and at defined postoperative follow-up intervals up to 2 years. Postoperative adverse events are also recorded. The preoperative and postoperative values are compared for each outcome measure, and the benefits and harms of the single-stage OGAAP-2 procedure will be compared with the results obtained using a previously employed 2-stage procedure.

Ethics and dissemination

This study has received ethics approval from the University of ...

Alizadeh, A, Warkiani, ME & Wang, M 2017, 'Manipulating electrokinetic conductance of nanofluidic channel by varying inlet pH of solution', Microfluidics and Nanofluidics, vol. 21, no. 3, pp. 1-15.
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© 2017, Springer-Verlag Berlin Heidelberg. The electrokinetic conductivity of micro-/nanofluidic systems, which strongly depends on the local solution properties (e.g., pH and ionic strength), has wide applications in nanosystems to control the system performance and ion rectification. Accurate and active manipulation of this parameter is proven to be very challenging since, in nanoscale, the ion transport is particularly dominated by the acquired surface charge on the solid–liquid interfaces. In this study, we propose an approach to manipulate the nanochannel electrokinetic conductivity by changing the pH value of the solution at the inlet in order to impose asymmetrical conditions inside nanochannel. The variable surface charge of walls is determined by considering the chemical adsorption on the solid–liquid interface and the electrical double layer interaction. The presented numerical model, which couples Poisson–Nernst–Planck and Navier–Stokes equations, can fully consider the electro-chemo-mechanical transport phenomena and predict the electrokinetic conductivity of nanofluidic channels with good accuracy. Modeling results show that the electrokinetic conductivity of the nanofluidic systems can be regulated by varying the solution pH at the inlet. It is revealed that the stronger electric double layers interaction can enhance the sensitivity of the nanochannel electrokinetic conductance to the inlet pH. This unique behavior of the nanochannel electrokinetic conductivity could broaden potential applications in biomedical, energy, and environmental systems using nanofluidic devices.

Asadnia, M, Khorasani, AM & Warkiani, ME 2017, 'An Accurate PSO-GA Based Neural Network to Model Growth of Carbon Nanotubes', Journal of Nanomaterials, vol. 2017, pp. 1-6.
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By combining particle swarm optimization (PSO) and genetic algorithms (GA) this paper offers an innovative algorithm to train artificial neural networks (ANNs) for the purpose of calculating the experimental growth parameters of CNTs. The paper explores experimentally obtaining data to train ANNs, as a method to reduce simulation time while ensuring the precision of formal physics models. The results are compared with conventional particle swarm optimization based neural network (CPSONN) and Levenberg–Marquardt (LM) techniques. The results show that PSOGANN can be successfully utilized for modeling the experimental parameters that are critical for the growth of CNTs.

Asadnia, M, Mousavi Ehteshami, SM, Chan, SH & Warkiani, ME 2017, 'Development of a fiber-based membraneless hydrogen peroxide fuel cell', RSC Advances, vol. 7, no. 65, pp. 40755-40760.
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Polyvinylidene fluoride (PVDF) electrospun nano-fiber is suggested as the substrate material for developing biocompatible membraneless hydrogen peroxide fuel cells.

Atallah, R, Li, JJ, Lu, W, Leijendekkers, R, Frölke, JP & Al Muderis, M 2017, 'Osseointegrated Transtibial Implants in Patients with Peripheral Vascular Disease', Journal of Bone and Joint Surgery, vol. 99, no. 18, pp. 1516-1523.
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Background: Osseointegration is an alternative treatment for amputees who are unable to wear or have difficulty wearing a socket prosthesis. Although the majority of limb amputations are due to vascular disease, such amputations have been perceived as a contraindication to osseointegration surgery. We report the outcomes of osseointegrated reconstruction in a series of 5 patients with limb amputation due to peripheral vascular disease. Methods: Five patients with transtibial amputation and a history of peripheral vascular disease who received an osseointegration implant from 2014 to 2015 were followed for 12 months. Clinical and functional outcomes were assessed, including pain, the amount of time the patient wore the prosthesis, mobility, walking ability, and quality of life. Adverse events, including infection, fracture, implant failure, revision surgery, additional amputation, and death, were monitored and recorded. Results: Five transtibial amputees (56 to 84 years of age) followed for 1 year after osseointegration surgery were included in this case series. The mobility of all patients was improved at the time of follow-up. Three patients were wheelchair-bound prior to the surgery but all 5 were able to walk and perform daily activities at the time of follow-up. Four of the 5 patients were pain-free at 12 months postoperatively, and all 5 were using the osseointegrated prosthesis. Two patients had a single episode of superficial soft-tissue infection. Conclusions: An osseointegrated implant may be considered a feasible alternative to the conventional socket pros...

Aya-Bonilla, CA, Marsavela, G, Freeman, JB, Lomma, C, Frank, MH, Khattak, MA, Meniawy, TM, Millward, M, Warkiani, ME, Gray, ES & Ziman, M 2017, 'Isolation and detection of circulating tumour cells from metastatic melanoma patients using a slanted spiral microfluidic device', Oncotarget, vol. 8, no. 40, pp. 67355-67368.
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Circulating Tumour Cells (CTCs) are promising cancer biomarkers. Several methods have been developed to isolate CTCs from blood samples. However, the isolation of melanoma CTCs is very challenging as a result of their extraordinary heterogeneity, which has hindered their biological and clinical study. Thus, methods that isolate CTCs based on their physical properties, rather than surface marker expression, such as microfluidic devices, are greatly needed in melanoma. Here, we assessed the ability of the slanted spiral microfluidic device to isolate melanoma CTCs via label-free enrichment. We demonstrated that this device yields recovery rates of spiked melanoma cells of over 80% and 55%, after one or two rounds of enrichment, respectively. Concurrently, a two to three log reduction of white blood cells was achieved with one or two rounds of enrichment, respectively. We characterised the isolated CTCs using multimarker flow cytometry, immunocytochemistry and gene expression. The results demonstrated that CTCs from metastatic melanoma patients were highly heterogeneous and commonly expressed stem-like markers such as PAX3 and ABCB5. The implementation of the slanted microfluidic device for melanoma CTC isolation enables further understanding of the biology of melanoma metastasis for biomarker development and to inform future treatment approaches.

Chandrakanthan, V, Kang, YC, Knezevic, K, Qiao, Q, Oliver, RA, Unnikrishnan, A, Beck, D, Lee, B, Brownlee, C, Power, C & Pimanda, JE 2017, 'Genetic Fate Mapping of Mesenchymal Stem-Like Cells in the Aorta-Gonad Mesonephros (AGM) and Their Contribution to Definitive Hematopoiesis', Mechanisms of Development, vol. 145, pp. S55-S56.
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Chen, W, Deng, W & Goldys, EM 2017, 'Light-Triggerable Liposomes for Enhanced Endolysosomal Escape and Gene Silencing in PC12 Cells', Molecular Therapy - Nucleic Acids, vol. 7, pp. 366-377.
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Liposomes are an effective gene and/or drug delivery system, widely used in biomedical applications including gene therapy and chemotherapy. Here, we designed a photo-responsive liposome (lipVP) loaded with a photosensitizer verteporfin (VP). This photosensitizer is clinically approved for photodynamic therapy (PDT). LipVP was employed as a DNA carrier for pituitary adenylyl cyclase-activating polypeptide (PACAP) receptor 1 (PAC1R) gene knockdown in PC12 cells. This has been done by incorporating PAC1R antisense oligonucleotides inside the lipVP cavity. Cells that have taken up the lipVP were exposed to light from a UV light source. As a result of this exposure, reactive oxygen species (ROS) were generated from VP, destabilizing the endolysosomal membranes and enhancing the liposomal release of antisense DNA into the cytoplasm. Endolysosomal escape of DNA was documented at different time points based on quantitative analysis of colocalization between fluorescently labeled DNA and endosomes and lysosomes. The released antisense oligonucleotides were found to silence PAC1R mRNA. The efficiency of this photo-induced gene silencing was demonstrated by a 74% ± 5% decrease in PAC1R fluorescence intensity. Following the light-induced DNA transfer into cells, cell differentiation with exposure to two kinds of PACAP peptides was observed to determine the cell phenotypic change after PAC1R gene knockdown.

Clement, S, Sobhan, M, Deng, W, Camilleri, E & Goldys, EM 2017, 'Nanoparticle-mediated singlet oxygen generation from photosensitizers', Journal of Photochemistry and Photobiology A: Chemistry, vol. 332, pp. 66-71.
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Dehbari, N, Tavakoli, J, Singh Khatrao, S & Tang, Y 2017, 'In situ polymerized hyperbranched polymer reinforced poly(acrylic acid) hydrogels', Materials Chemistry Frontiers, vol. 1, no. 10, pp. 1995-2004.
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A novel hyperbranched polymer reinforced poly(acrylic acid) hydrogel with high water swelling abilities was synthesized by one-step in situ polymerization.

Dehbari, N, Tavakoli, J, Zhao, J & Tang, Y 2017, 'In situ formed internal water channels improving water swelling and mechanical properties of water swellable rubber composites', Journal of Applied Polymer Science, vol. 134, no. 9, pp. 1-6.
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ABSTRACTIn this study, electrospun nanofibers of poly (vinyl alcohol) (PVA) and styrene–butadiene–styrene triblock copolymer (SBS) were employed in conventional water‐swellable rubber (WSR) to design WSR composites with improved water swelling and mechanical properties. With the introduction of PVA nanofibers, considerable improvement in elasticity, strength, and water‐swelling behavior was observed. After immersion, PVA nanofibers dissolved within the composite to in situ form water channels to connect isolated super‐absorbent polymers (SAPs). Those water channels led to an increase in water uptake by the WSR composite. Furthermore, the secondary water‐swelling behaviors of the WSR composite showed a remarkable increase in swelling rate as well as in mechanical properties. The addition of SBS nanofibers had a marked impact on the mechanical properties of the WSR composite. Their roles became more pronounced after water immersion. The proposed enhancement mechanism is also discussed. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44548.

Figtree, GA, Bubb, KJ, Tang, O, Kizana, E & Gentile, C 2017, 'Vascularized Cardiac Spheroids as Novel 3D in vitro Models to Study Cardiac Fibrosis', Cells Tissues Organs, vol. 204, no. 3-4, pp. 191-198.
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Spheroid cultures are among the most explored cellular biomaterials used in cardiovascular research, due to their improved integration of biochemical and physiological features of the heart in a defined architectural three-dimensional microenvironment when compared to monolayer cultures. To further explore the potential use of spheroid cultures for research, we engineered a novel in vitro model of the heart with vascularized cardiac spheroids (VCSs), by coculturing cardiac myocytes, endothelial cells, and fibroblasts isolated from dissociated rat neonatal hearts (aged 1-3 days) in hanging drop cultures. To evaluate the validity of VCSs in recapitulating pathophysiological processes typical of the in vivo heart, such as cardiac fibrosis, we then treated VCSs with transforming growth factor beta 1 (TGFβ1), a known profibrotic agent. Our mRNA analysis demonstrated that TGFβ1-treated VCSs present elevated levels of expression of connective tissue growth factor, fibronectin, and TGFβ1 when compared to control cultures. We demonstrated a dramatic increase in collagen deposition following TGFβ1 treatment in VCSs in the PicroSirius Red-stained sections. Doxorubicin, a renowned cardiotoxic and profibrotic agent, triggered apoptosis and disrupted vascular networks in VCSs. Taken together, our findings demonstrate that VCSs are a valid model for the study of the mechanisms involved in cardiac fibrosis, with the potential to be used to investigate novel mechanisms and therapeutics for treating and preventing cardiac fibrosis in vitro.

Gerami, A, Armstrong, RT, Johnston, B, Warkiani, ME, Mosavat, N & Mostaghimi, P 2017, 'Coal-on-a-Chip: Visualizing Flow in Coal Fractures', Energy & Fuels, vol. 31, no. 10, pp. 10393-10403.
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© 2017 American Chemical Society. Geomaterial microfluidics are the next generation of tools necessary for studying fluid flows related to subsurface engineering technologies. Traditional microfluidic devices do not capture surface wettability and roughness parameters that can have a significant influence on porous media flows. This is particularly important for coal seam gas reservoirs in which methane gas is transported through a well-developed system of natural fractures that display unique wettability and roughness characteristics. A coal geomaterial microfluidic device can be generated by etching a fracture pattern on a coal surface by using three-dimensional laser micromachining; however, it is unclear if the resulting surface properties are representative of real coal. In an effort to generate a realistic coal microfluidic device, we characterize coal surface roughness properties from real coal cleats. We then compare these results to the roughness of the patterns, generated from laser etching. Roughness measurements in real coal fractures show that cleats and microfractures are mostly oriented parallel to the coal beddings rather than perpendicular to the bedding, which is important when selecting coal for fabrication of a microfluidic device since we find that the natural microfractures influence the resulting roughness of etched fractures. We also compare resulting coal/brine/gas contact angles under static and dynamics conditions. The contact angle for coal is highly heterogeneous. Surface roughness and pore pressure may influence the contact angle. With the aid of the coal geomaterial device, the effect of these parameters on coal wettability can be explored and a range of possible coal contact angles can be visualized and represented. The geomaterial fabrication, as outlined herein, provides a tool to capture more realistic coal surface properties in microfluidics experiments.

Goharimanesh, M, Javid, SM, Bazaz, SR & Rostami, H 2017, 'Reducing ice accretion using design of experiments based on Taguchi method', Journal of Applied Science and Engineering, vol. 20, no. 2, pp. 165-172.
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This paper presents a study in which an attempt has been made to reduce ice accretion of aircraft wings by optimizing the design parameters using Taguchi method. CFD have been used for simulating ice accretion in various conditions. The effects of the seven design parameters such as altitude, angle of attack, yaw angle, icing temperature, air speed, characteristic length and median volume diameter (MVD) are investigated. The analysis of the results then are shown in S/N ration plots which indicating which combination of parameters leads to minimize ice accretion. Analysis of variance demonstrates that, among the design parameters, as opposed to characteristic length and altitudes, having the lowest effect, MVD and air speed have the highest one. In the end, a general linear model for the amount of ice is obtained to show a proper correlation between the mass of ice created and other parameters.

Gourlay, ML, Ritter, VS, Fine, JP, Overman, RA, Schousboe, JT, Cawthon, PM, Orwoll, ES, Nguyen, TV, Lane, NE, Cummings, SR, Kado, DM, Lapidus, JA, Diem, SJ & Ensrud, KE 2017, 'Comparison of fracture risk assessment tools in older men without prior hip or spine fracture: the MrOS study', Archives of Osteoporosis, vol. 12, no. 1, pp. 1-11.
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© 2017, International Osteoporosis Foundation and National Osteoporosis Foundation. Abstract: Summary: Femoral neck bone mineral density (BMD), age plus femoral neck BMD T score, and three externally generated fracture risk tools had similar accuracy to identify older men who developed osteoporotic fractures. Risk tools with femoral neck BMD performed better than those without BMD. The externally developed risk tools were poorly calibrated. Introduction: We compared the performance of fracture risk assessment tools in older men, accounting for competing risks including mortality. Methods: A comparative ROC curve analysis assessed the ability of the QFracture, FRAX® and Garvan fracture risk tools, and femoral neck bone mineral density (BMD) T score with or without age to identify incident fracture in community-dwelling men aged 65 years or older (N = 4994) without hip or clinical vertebral fracture or antifracture treatment at baseline. Results: Among risk tools calculated with BMD, the discriminative ability to identify men with incident hip fracture was similar for FRAX (AUC 0.77, 95% CI 0.73, 0.81), the Garvan tool (AUC 0.78, 95% CI 0.74, 0.82), age plus femoral neck BMD T score (AUC 0.79, 95% CI 0.75, 0.83), and femoral neck BMD T score alone (AUC 0.76, 95% CI 0.72, 0.81). Among risk tools calculated without BMD, the discriminative ability to identify hip fracture was similar for QFracture (AUC 0.69, 95% CI 0.66, 0.73), FRAX (AUC 0.70, 95% CI 0.66, 0.73), and the Garvan tool (AUC 0.71, 95% CI 0.67, 0.74). Correlated ROC curve analyses revealed better diagnostic accuracy for risk scores calculated with BMD compared with QFracture (P < 0.0001). Calibration was good for the internally generated BMD T score predictor with or without age and poor for the externally developed risk tools. Conclusion: In untreated older men without fragility fractures at baseline, an age plus femoral neck BMD T score classifier identified men with incident hip fracture as ac...

Gourlay, ML, Ritter, VS, Fine, JP, Overman, RA, Schousboe, JT, Cawthon, PM, Orwoll, ES, Nguyen, TV, Lane, NE, Cummings, SR, Kado, DM, Lapidus, JA, Diem, SJ & Ensrud, KE 2017, 'Correction to: Comparison of fracture risk assessment tools in older men without prior hip or spine fracture: the MrOS study', Archives of Osteoporosis, vol. 12, no. 1, pp. 99-99.
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Owing to an oversight by the authors, the acknowledgments were incomplete.

Guan, R, Zhang, L, Su, QP, Mickolajczyk, KJ, Chen, G-Y, Hancock, WO, Sun, Y, Zhao, Y & Chen, Z 2017, 'Crystal structure of Zen4 in the apo state reveals a missing conformation of kinesin', Nature Communications, vol. 8, no. 1.
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AbstractKinesins hydrolyse ATP to transport intracellular cargoes along microtubules. Kinesin neck linker (NL) functions as the central mechano-chemical coupling element by changing its conformation through the ATPase cycle. Here we report the crystal structure of kinesin-6 Zen4 in a nucleotide-free, apo state, with the NL initial segment (NIS) adopting a backward-docked conformation and the preceding α6 helix partially melted. Single-molecule fluorescence resonance energy transfer (smFRET) analyses indicate the NIS of kinesin-1 undergoes similar conformational changes under tension in the two-head bound (2HB) state, whereas it is largely disordered without tension. The backward-docked structure of NIS is essential for motility of the motor. Our findings reveal a key missing conformation of kinesins, which provides the structural basis of the stable 2HB state and offers a tension-based rationale for an optimal NL length to ensure processivity of the motor.

Ha, DT, Dang, TQ, Tran, NV, Pham, TNT, Nguyen, ND & Nguyen, TV 2017, 'Correction: Corrigendum: Development and validation of a prognostic model for predicting 30-day mortality risk in medical patients in emergency department (ED)', Scientific Reports, vol. 7, no. 1, pp. 1-2.
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Scientific Reports 7: Article number: 46474; published online: 12 April 2017; updated: 22 December 2017. This Article contains errors in Figure 3 where the authors calculated the probability of survival instead of the probability of mortality. The correct Figure 3 appears below as Figure 1.

Ha, DT, Dang, TQ, Tran, NV, Pham, TNT, Nguyen, ND & Nguyen, TV 2017, 'Development and validation of a prognostic model for predicting 30-day mortality risk in medical patients in emergency department (ED)', Scientific Reports, vol. 7, no. 1.
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AbstractThe primary aim of this prospective study is to develop and validate a new prognostic model for predicting the risk of mortality in Emergency Department (ED) patients. The study involved 1765 patients in the development cohort and 1728 in the validation cohort. The main outcome was mortality up to 30 days after admission. Potential risk factors included clinical characteristics, vital signs, and routine haematological and biochemistry tests. The Bayesian Model Averaging method within the Cox’s regression model was used to identify independent risk factors for mortality. In the development cohort, the incidence of 30-day mortality was 9.8%, and the following factors were associated with a greater risk of mortality: male gender, increased respiratory rate and serum urea, decreased peripheral oxygen saturation and serum albumin, lower Glasgow Coma Score, and admission to intensive care unit. The area under the receiver operating characteristic curve for the model with the listed factors was 0.871 (95% CI, 0.844–0.898) in the development cohort and 0.783 (95% CI, 0.743–0.823) in the validation cohort. Calibration analysis found a close agreement between predicted and observed mortality risk. We conclude that the risk of mortality among ED patients could be accurately predicted by using common clinical signs and biochemical tests.

Hao, H, Su, Q, Zhao, S & Sun, Y 2017, 'Golgi Microtubules are Hyper-Acetylated and Participate in Fast Cargo Trafficking', Biophysical Journal, vol. 112, no. 3, pp. 238a-238a.
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Ho-Le, TP, Center, JR, Eisman, JA, Nguyen, HT & Nguyen, TV 2017, 'Prediction of Bone Mineral Density and Fragility Fracture by Genetic Profiling', Journal of Bone and Mineral Research, vol. 32, no. 2, pp. 285-293.
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ABSTRACT   Although the susceptibility to fracture is partly determined by genetic factors, the contribution of newly discovered genetic variants to fracture prediction is still unclear. This study sought to define the predictive value of a genetic profiling for fracture prediction. Sixty-two bone mineral density (BMD)-associated single-nucleotide polymorphisms (SNPs) were genotyped in 557 men and 902 women who had participated in the Dubbo Osteoporosis Epidemiology Study. The incidence of fragility fracture was ascertained from X-ray reports between 1990 and 2015. Femoral neck BMD was measured by dual-energy X-ray absorptiometry. A weighted polygenic risk score (genetic risk score [GRS]) was created as a function of the number of risk alleles and their BMD-associated regression coefficients for each SNP. The association between GRS and fracture risk was assessed by the Cox proportional hazards model. Individuals with greater GRS had lower femoral neck BMD (p &lt; 0.01), but the variation in GRS accounted for less than 2% of total variance in BMD. Each unit increase in GRS was associated with a hazard ratio of 1.20 (95% CI, 1.04 to 1.38) for fracture, and this association was independent of age, prior fracture, fall, and in a subset of 33 SNPs, independent of femoral neck BMD. The significant association between GRS and fracture was observed for the vertebral and wrist fractures, but not for hip fracture. The area under the receiver-operating characteristic (ROC) curve (AUC) for the model with GRS and clinical risk factors was 0.71 (95% CI, 0.68 to 0.74). With GRS, the correct reclassification of fracture versus nonfracture ranged from 12% for hip fracture to 23% for wrist fracture. A genetic profiling of BMD- associated genetic variants could improve the accuracy of fracture prediction over and above that of clinical risk factors ...

Ho-Pham, LT & Nguyen, TV 2017, 'The Vietnam Osteoporosis Study: Rationale and design', Osteoporosis and Sarcopenia, vol. 3, no. 2, pp. 90-97.
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Objectives:Osteoporosis and fracture impose a significant health care burden on the contemporary populations in developing countries. The Vietnam Osteoporosis Study (VOS) sought to assess the burden of osteoporosis and its comorbidities in men and women. Methods:The study was designed as a population-based family investigation in which families were randomly recruited from Ho Chi Minh City, Vietnam. Individuals were assessed for bone health, including bone mineral density (BMD) and body composition and trabecular and cortical bone properties by pQCT (peripheral quantitative computed tomography). Fasting blood samples were obtained for the analysis of plasma glucose, glycosylated hemoglobin, and bone turnover markers. Genomic DNA extraction from whole blood samples for further genetic and genomic analyses. Results:We have recruited more than 4157 individuals from 817 families. The average age of participants was 51, with approximately 45% of the individuals aged 50 years and older. Approximately 3% of participants were obese (body mass index ≥ 30 kg/m2), and 21% were overweight. Notably, 11% of participants aged 40 years and older were diabetic. Among those aged 50 years and older, approximately 14% of women and 5% of men had osteoporosis (i.e., femoral neck BMD T-scores ≤ -2.5). There were modest correlations between volumetric BMD and areal BMD. Conclusions:VOS is a major bone research project in Vietnam aimed at comprehensively documenting the burden osteoporosis, its co-occurrence of chronic diseases, and their underlying etiologies. The Study will make important contributions to the literature of bone health worldwide.

Ho-Pham, LT, Lai, TQ, Nguyen, UDT, Bui, QV & Nguyen, TV 2017, 'Delineating the Relationship Between Leptin, Fat Mass, and Bone Mineral Density: A Mediation Analysis', Calcified Tissue International, vol. 100, no. 1, pp. 13-19.
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© 2016, Springer Science+Business Media New York. To test the hypothesis that the relationship between fat mass (FM) and bone mineral density (BMD) is mediated by leptin. The study involved 611 individuals aged 20–89 years who were randomly sampled from Ho Chi Minh City (Vietnam). BMD at the femoral neck (FN), lumbar spine (LS), and whole body (WB) was measured by DXA. Lean mass and FM were derived from the WB DXA scan. Leptin was measured by ELISA (DRG Diagnostics, Germany). The regression method was used to partition the variance of leptin and FM on BMD. The mediated effect of leptin was analyzed by the mediation analysis model. In the multiple linear regression, leptin, FM, and age collectively accounted for ~34 % variation in FNBMD in men and women. However, only 0.5 % of this explained variance was due to leptin. Of the total effect of FM on FNBMD, the mediated effect of leptin accounted for 6.1 % (P = 0.38) in men and 7.1 % (P = 0.99) in women. The same trend was observed for LS and WBBMD. These data suggest that greater FM is associated with greater BMD, but the association is not mediated by leptin, and that leptin has a non-significant influence on bone mass.

Ho-Pham, LT, Nguyen, UDT, Tran, TX & Nguyen, TV 2017, 'Discordance in the diagnosis of diabetes: Comparison between HbA1c and fasting plasma glucose', PLOS ONE, vol. 12, no. 8, pp. e0182192-e0182192.
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© 2017 Ho-Pham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objective HbA1c has been introduced as a complementary diagnostic test for diabetes, but its impact on disease prevalence is unknown. This study evaluated the concordance between HbA1c and fasting plasma glucose (FPG) in the diagnosis of diabetes in the general population. Materials and methods The study was designed as a population based investigation, with participants being sampled from the Ho Chi Minh City, Vietnam. Blood samples were collected after overnight fasting and analyzed within 4 hours after collection. HbA1c was measured with high pressure liquid chromatography (Arkray Adams, Japan). FPG was measured by the hexokinase method (Advia Autoanalyzer; Bayer Diagnostics, Germany). Diabetes was defined as HbA1c 6.5% or FPG 7.0 mmol/L. Prediabetes was classified as HbA1c between 5.7% and 6.4%. Results The study included 3523 individuals (2356 women) aged 30 years and above. Based on the HbA1c test, the prevalence of diabetes and prediabetes was 9.7% (95%CI, 8.7–10.7%; n = 342) and 34.6% (33.0–36.2; n = 1219), respectively. Based on the FPG test, the prevalence of diabetes and prediabetes was 6.3% (95%CI, 5.5–7.2%; n = 223) and 12.1% (11.1–13.2; n = 427). Among the 427 individuals identified by FPG as 'pre-diabetes', 28.6% were classified as diabetes by HbA1c test. The weighted kappa statistic of concordance between HbA1c and FPG was 0.55, with most of the discordance being in the prediabetes group. Conclusion These data indicate that there is a significant discordance in the diagnosis of diabetes between FPG and HbA1c measurements, and the discordance could have significant impact on clinical practice. FPG appears to underestimate the burden of undiagnosed diabetes.

Jiang, L, Gentile, C, Lauto, A, Cui, C, Song, Y, Romeo, T, Silva, SM, Tang, O, Sharma, P, Figtree, G, Gooding, JJ & Mawad, D 2017, 'Versatile Fabrication Approach of Conductive Hydrogels via Copolymerization with Vinyl Monomers', ACS Applied Materials & Interfaces, vol. 9, no. 50, pp. 44124-44133.
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Functionalized poly(ethylene dioxythiophene) (f-PEDOT) was copolymerized with two vinyl monomers of different hydrophilicity, acrylic acid and hydroxyethyl methacrylate, to produce electroconductive hydrogels with a range of physical and electronic properties. These hydrogels not only possessed tailored physical properties, such as swelling ratios and mechanical properties, but also displayed electroactivity dependent on the chemical composition of the network. Raman spectroscopy indicated that the functional PEDOT in the hydrogels is in an oxidized form, most likely accounting for the good electrochemical response of the hydrogels observed in physiological buffer. In vitro cell studies showed that cardiac cells respond differently when seeded on hydrogel substrates with different compositions. This study presents a facile approach for the fabrication of electroconductive hydrogels with a range of properties, paving the way for scaffolds that can meet the requirements of different electroresponsive tissues.

Kautzka, Z, Clement, S, Goldys, EM & Deng, W 2017, 'Light-triggered liposomal cargo delivery platform incorporating photosensitizers and gold nanoparticles for enhanced singlet oxygen generation and increased cytotoxicity', International Journal of Nanomedicine, vol. Volume 12, pp. 969-977.
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Keam, SP, Sobala, A, ten Have, S & Hutvagner, G 2017, 'tRNA-Derived RNA Fragments Associate with Human Multisynthetase Complex (MSC) and Modulate Ribosomal Protein Translation', Journal of Proteome Research, vol. 16, no. 2, pp. 413-420.
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© 2016 American Chemical Society. The functionality of small RNAs from abundant species of 'housekeeping' noncoding RNAs (e.g., rRNA, tRNA, snRNA, snoRNA, etc.) remains a highly studied topic. The current state of research on short RNAs derived from transfer RNA (tRNA), called tRNA-derived fragments (tRFs), has been restricted largely to expression studies and limited functional studies. 5′ tRFs are known translational inhibitors in mammalian cells, yet little is known about their functionality. Here we report on the first experimental evidence of the tRF protein interactome, identifying the mammalian multisynthetase complex as the primary interactor of the 5′ tRF Gln19. We also present proteome-wide SILAC evidence that 5′ tRFs increase ribosomal and poly(A)-binding protein translation.

Kulasinghe, A, Perry, C, Kenny, L, Warkiani, ME, Nelson, C & Punyadeera, C 2017, 'PD-L1 expressing circulating tumour cells in head and neck cancers', BMC Cancer, vol. 17, no. 1, pp. 1-6.
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© 2017 The Author(s). Background: Blockade of the PD-1/PD-L1 immune checkpoint pathway is emerging as a promising immunotherapeutic approach for the management and treatment of head and neck cancer patients who do not respond to 1st/2nd line therapy. However, as checkpoint inhibitors are cost intensive, identifying patients who would most likely benefit from anti PD-L1 therapy is required. Developing a non-invasive technique would be of major benefit to the patient and to the health care system. Case presentation: We report the case of a 56 year old man affected by a supraglottic squamous cell carcinoma (SCC). A CT scan showed a 20 mm right jugulodigastric node and suspicious lung lesions. The lung lesion was biopsied and confirmed to be consistent with SCC. The patient was offered palliative chemotherapy. At the time of presentation, a blood sample was taken for circulating tumour cell (CTC) analysis. The dissemination of cancer was confirmed by the detection of CTCs in the peripheral blood of the patient, measured by the CellSearch System (Janssen Diagnostics). Using marker-independent, low-shear spiral microfluidic technology combined with immunocytochemistry, CTC clusters were found in this patient at the same time point, expressing PD-L1. Conclusion: This report highlights the potential use of CTCs to identify patients which might respond to anti PD-L1 therapy.

Kulasinghe, A, Tran, THP, Blick, T, O’Byrne, K, Thompson, EW, Warkiani, ME, Nelson, C, Kenny, L & Punyadeera, C 2017, 'Enrichment of circulating head and neck tumour cells using spiral microfluidic technology', Scientific Reports, vol. 7, no. 1, pp. 1-10.
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AbstractWhilst locoregional control of head and neck cancers (HNCs) has improved over the last four decades, long-term survival has remained largely unchanged. A possible reason for this is that the rate of distant metastasis has not changed. Such disseminated disease is reflected in measurable levels of cancer cells in the blood of HNC patients, referred to as circulating tumour cells (CTCs). Numerous marker-independent techniques have been developed for CTC isolation and detection. Recently, microfluidics-based platforms have come to the fore to avoid molecular bias. In this pilot, proof of concept study, we evaluated the use of the spiral microfluidic chip for CTC enrichment and subsequent detection in HNC patients. CTCs were detected in 13/24 (54%) HNC patients, representing both early to late stages of disease. Importantly, in 7/13 CTC-positive patients, CTC clusters were observed. This is the first study to use spiral microfluidics technology for CTC enrichment in HNC.

Kwon, T, Prentice, H, Oliveira, JD, Madziva, N, Warkiani, ME, Hamel, J-FP & Han, J 2017, 'Microfluidic Cell Retention Device for Perfusion of Mammalian Suspension Culture', Scientific Reports, vol. 7, no. 1, pp. 1-11.
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AbstractContinuous production of biologics, a growing trend in the biopharmaceutical industry, requires a reliable and efficient cell retention device that also maintains cell viability. Current filtration methods, such as tangential flow filtration using hollow-fiber membranes, suffer from membrane fouling, leading to significant reliability and productivity issues such as low cell viability, product retention, and an increased contamination risk associated with filter replacement. We introduce a novel cell retention device based on inertial sorting for perfusion culture of suspended mammalian cells. The device was characterized in terms of cell retention capacity, biocompatibility, scalability, and long-term reliability. This technology was demonstrated using a high concentration (>20 million cells/mL) perfusion culture of an IgG1-producing Chinese hamster ovary (CHO) cell line for 18–25 days. The device demonstrated reliable and clog-free cell retention, high IgG1 recovery (>99%) and cell viability (>97%). Lab-scale perfusion cultures (350 mL) were used to demonstrate the technology, which can be scaled-out with parallel devices to enable larger scale operation. The new cell retention device is thus ideal for rapid perfusion process development in a biomanufacturing workflow.

Lal, S, Hall, RM & Tipper, JL 2017, 'Concentration and size distribution data of silicon nitride nanoparticles measured using nanoparticle tracking analysis', Data in Brief, vol. 15, pp. 821-823.
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© 2017 This article refers to the paper “A novel method for isolation and recovery of ceramic nanoparticles and metal wear debris from serum lubricants at ultra-low wear rates” (Lal et al., 2016) [1] and describes the concentration and size distribution data of silicon nitride nanoparticles measured using nanoparticle tracking analysis (NTA). A NanoSight LM10 instrument was used to capture the video data of silicon nitride nanoparticles moving under Brownian motion in the water. The video data was then analyzed using the NanoSight NTA software. This article also describes a methodology for calculating the percentage recovery of a nanoparticle isolation process.

Law, AMK, Lim, E, Ormandy, CJ & Gallego-Ortega, D 2017, 'The innate and adaptive infiltrating immune systems as targets for breast cancer immunotherapy', Endocrine-Related Cancer, vol. 24, no. 4, pp. R123-R144.
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A cancer cell-centric view has long dominated the field of cancer biology. Research efforts have focussed on aberrant cancer cell signalling pathways and on changes to cancer cell DNA. Mounting evidence demonstrates that many cancer-associated cell types within the tumour stroma co-evolve and support tumour growth and development, greatly modifying cancer cell behaviour, facilitating invasion and metastasis and controlling dormancy and sensitivity to drug therapy. Thus, these stromal cells represent potential targets for cancer therapy. Among these cell types, immune cells have emerged as a promising target for therapy. The adaptive and the innate immune system play an important role in normal mammary development and breast cancer. The number of infiltrating adaptive immune system cells with tumour-rejecting capacity, primarily, T lymphocytes, is lower in breast cancer compared with other cancer types, but infiltration occurs in a large proportion of cases. There is strong evidence demonstrating the importance of the immunosuppressive role of the innate immune system during breast cancer progression. A consideration of components of both the innate and the adaptive immune system is essential for the design and development of immunotherapies in breast cancer. In this review, we focus on the importance of immunosuppressive myeloid-derived suppressor cells (MDSCs) as potential targets for breast cancer therapy.

Law, AMK, Lim, E, Ormandy, CJ & Gallego-Ortega, D 2017, 'The innate and adaptive infiltrating immune systems as targets for breast cancer immunotherapy', Endocrine-Related Cancer, vol. 24, no. 7, pp. X1-X1.
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Law, AMK, Yin, JXM, Castillo, L, Young, AIJ, Piggin, C, Rogers, S, Caldon, CE, Burgess, A, Millar, EKA, O’Toole, SA, Gallego-Ortega, D, Ormandy, CJ & Oakes, SR 2017, 'Andy’s Algorithms: new automated digital image analysis pipelines for FIJI', Scientific Reports, vol. 7, no. 1.
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AbstractQuantification of cellular antigens and their interactions via antibody-based detection methods are widely used in scientific research. Accurate high-throughput quantitation of these assays using general image analysis software can be time consuming and challenging, particularly when attempted by users with limited image processing and analysis knowledge. To overcome this, we have designed Andy’s Algorithms, a series of automated image analysis pipelines for FIJI, that permits rapid, accurate and reproducible batch-processing of 3,3′-diaminobenzidine (DAB) immunohistochemistry, proximity ligation assays (PLAs) and other common assays. Andy’s Algorithms incorporates a step-by-step tutorial and optimization pipeline to make batch image analysis simple for the untrained user and adaptable across laboratories. Andy’s algorithms provide a simpler, faster, standardized work flow compared to existing programs, while offering equivalent performance and additional features, in a free to use open-source application of FIJI. Andy’s Algorithms are available at GitHub, publicly accessed at https://github.com/andlaw1841/Andy-s-Algorithm.

Li, JJ, Roohani-Esfahani, S-I, Kim, K, Kaplan, DL & Zreiqat, H 2017, 'Silk coating on a bioactive ceramic scaffold for bone regeneration: effective enhancement of mechanical and in vitro osteogenic properties towards load-bearing applications', Journal of Tissue Engineering and Regenerative Medicine, vol. 11, no. 6, pp. 1741-1753.
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Bioactive ceramic scaffolds represent competitive choices for clinical bone reconstruction, but their widespread use is restricted by inherent brittleness and weak mechanical performance under load. This study reports the development of strong and tough bioactive scaffolds suitable for use in load-bearing bone reconstruction. A strong and bioactive ceramic scaffold (strontium-hardystonite-gahnite) is combined with single and multiple coating layers of silk fibroin to enhance its toughness, producing composite scaffolds which match the mechanical properties of cancellous bone and show enhanced capacity to promote in vitro osteogenesis. Also reported for the first time is a comparison of the coating effects obtained when a polymeric material is coated on ceramic scaffolds with differing microstructures, namely the strontium-hardystonite-gahnite scaffold with high-density struts as opposed to a conventional ceramic scaffold, such as biphasic calcium phosphate, with low-density struts. The results show that silk coating on a unique ceramic scaffold can lead to simple and effective enhancement of its mechanical and biological properties to suit a wider range of applications in clinical bone reconstruction, and also establish the influence of ceramic microstructure on the effectiveness of silk coating as a method of reinforcement when applied to different types of ceramic bone graft substitutes. Copyright © 2015 John Wiley & Sons, Ltd.

Liu, K, Beck, D, Thoms, JAI, Liu, L, Zhao, W, Pimanda, JE & Zhou, X 2017, 'Annotating function to differentially expressed LincRNAs in myelodysplastic syndrome using a network-based method', Bioinformatics, vol. 33, no. 17, pp. 2622-2630.
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Abstract Motivation Long non-coding RNAs (lncRNAs) have been implicated in the regulation of diverse biological functions. The number of newly identified lncRNAs has increased dramatically in recent years but their expression and function have not yet been described from most diseases. To elucidate lncRNA function in human disease, we have developed a novel network based method (NLCFA) integrating correlations between lncRNA, protein coding genes and noncoding miRNAs. We have also integrated target gene associations and protein-protein interactions and designed our model to provide information on the combined influence of mRNAs, lncRNAs and miRNAs on cellular signal transduction networks. Results We have generated lncRNA expression profiles from the CD34+ haematopoietic stem and progenitor cells (HSPCs) from patients with Myelodysplastic syndromes (MDS) and healthy donors. We report, for the first time, aberrantly expressed lncRNAs in MDS and further prioritize biologically relevant lncRNAs using the NLCFA. Taken together, our data suggests that aberrant levels of specific lncRNAs are intimately involved in network modules that control multiple cancer-associated signalling pathways and cellular processes. Importantly, our method can be applied to prioritize aberrantly expressed lncRNAs for functional validation in other diseases and biological contexts. Availability and implementation The method is implemented in R language and Matlab. Supplementary information ...

Ma, C, Xu, X, Wang, F, Zhou, Z, Liu, D, Zhao, J, Guan, M, Lang, CI & Jin, D 2017, 'Optimal Sensitizer Concentration in Single Upconversion Nanocrystals', Nano Letters, vol. 17, no. 5, pp. 2858-2864.
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© 2017 American Chemical Society. Each single upconversion nanocrystal (UCNC) usually contains thousands of photon sensitizers and hundreds of photon activators to up-convert near-infrared photons into visible and ultraviolet emissions. Though in principle further increasing the sensitizers’ concentration will enhance the absorption efficiency to produce brighter nanocrystals, typically 20% of Yb3+ ions has been used to avoid the so-called “concentration quenching” effect. Here we report that the concentration quenching effect does not limit the sensitizer concentration and NaYbF4 is the most bright host matrix. Surface quenching and the large size of NaYbF4 nanocrystals are the only factors limiting this optimal concentration. Therefore, we further designed sandwich nanostructures of NaYbF4 between a small template core to allow an epitaxial growth of the size-tunable NaYbF4 shell enclosed by an inert shell to minimize surface quenching. As a result, the suspension containing 25.2 nm sandwich structure UCNCs is 1.85 times brighter than the homogeneously doped ones, and the brightness of each single 25.2 nm heterogeneous UCNC is enhanced by nearly 3 times compared to the NaYF4: 20% Yb3+, 4% Tm3+ UCNCs in similar sizes. Particularly, the blue emission intensities of the UCNCs with the sandwich structure in the size of 13.6 and 25.2 nm are 1.36 times and 3.78 times higher than that of the monolithic UCNCs in the similar sizes. Maximizing the sensitizer concentration will accelerate the development of brighter and smaller UCNCs as more efficient biomolecule probes or photon energy converters.

Mills, N, Lu, W, Li, JJ & Al Muderis, M 2017, 'Osseointegration as Treatment for a Knee Disarticulation Because of a Congenital Femoral Deficiency', JBJS Case Connector, vol. 7, no. 4, pp. e76-e76.
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Case: A 25-year-old woman underwent osseointegration surgery as treatment for an amputation that had been performed because of congenital femoral deficiency. The undersized custom-designed implant for the congenitally hypoplastic femur subsequently loosened, causing substantial pain and loss of function. The patient underwent revision surgery with a larger standard-sized osseointegration implant, and experienced no additional complications. Conclusion: This case demonstrates the possibility of stimulating a hypertrophic response in underdeveloped bone, which allows the subsequent insertion of a larger implant with greater stability. Similar procedures can be considered for the treatment of patients who had amputations because of congenital deficiencies, in order to produce improved outcomes and reduce the risk of additional complications.

Nguyen, TV 2017, 'Air pollution: a largely neglected risk factor for osteoporosis', The Lancet Planetary Health, vol. 1, no. 8, pp. e311-e312.
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Nguyen, TV 2017, 'Individualized Assessment of Fracture Risk: Contribution of “Osteogenomic Profile”', Journal of Clinical Densitometry, vol. 20, no. 3, pp. 353-359.
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Over the past decade, several genetic variants or genes for osteoporosis have been identified through genome-wide association studies and candidate gene association studies. These genetic variants are common in the general population but have modest effect sizes, with odds ratio ranging from 1.1 to 1.5. Thus, the utility of any single variant is limited. However, theoretical and empirical studies have suggested that a profiling of multiple variants that are associated with bone phenotypes (i.e., "osteogenomic profile") can improve the accuracy of fracture prediction and classification beyond that obtained by conventional clinical risk factors. These results support the view that an osteogenomic profile, when integrated into existing models, can help clinicians and patients alike to better assess the risk fracture for an individual, and raise the possibility of personalized osteoporosis care.

Nguyen, TV & Eisman, JA 2017, 'Fracture Risk Assessment: From Population to Individual', Journal of Clinical Densitometry, vol. 20, no. 3, pp. 368-378.
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© 2017 The International Society for Clinical Densitometry Fracture caused by osteoporosis remains a major public health burden on contemporary populations because fracture is associated with a substantial increase in the risk of mortality. Early identification of high-risk individuals for prevention is a priority in osteoporosis research. Over the past decade, few risk prediction models, including the Garvan Fracture Risk Calculator (Garvan) and FRAX®, have been developed to provide absolute (individualized) risk of fracture. Recent validation studies suggested that the area under the receiver operating characteristic curve in fracture discrimination ranged from 0.61 to 0.83 for FRAX® and from 0.63 to 0.88 for Garvan, with hip fractures having a better discrimination than fragility fractures as a group. Although the prognostic performance of Garvan and FRAX® for fracture prediction is not perfect and there is room for further improvement, these predictive models can aid patients and doctors communicate about fracture risk in the medium term and to make rational decisions. However, the application of these predictive models in making decisions for an individual should take into account the individual's perception of the importance of fracture relative to other diseases.

Nguyen, TV, Ho-Le, TP & Le, UV 2017, 'International collaboration in scientific research in Vietnam: an analysis of patterns and impact', Scientometrics, vol. 110, no. 2, pp. 1035-1051.
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No, Y, Li, J & Zreiqat, H 2017, 'Doped Calcium Silicate Ceramics: A New Class of Candidates for Synthetic Bone Substitutes', Materials, vol. 10, no. 2, pp. 153-153.
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Doped calcium silicate ceramics (DCSCs) have recently gained immense interest as a new class of candidates for the treatment of bone defects. Although calcium phosphates and bioactive glasses have remained the mainstream of ceramic bone substitutes, their clinical use is limited by suboptimal mechanical properties. DCSCs are a class of calcium silicate ceramics which are developed through the ionic substitution of calcium ions, the incorporation of metal oxides into the base binary xCaO-ySiO₂ system, or a combination of both. Due to their unique compositions and ability to release bioactive ions, DCSCs exhibit enhanced mechanical and biological properties. Such characteristics offer significant advantages over existing ceramic bone substitutes, and underline the future potential of adopting DCSCs for clinical use in bone reconstruction to produce improved outcomes. This review will discuss the effects of different dopant elements and oxides on the characteristics of DCSCs for applications in bone repair, including mechanical properties, degradation and ion release characteristics, radiopacity, and biological activity (in vitro and in vivo). Recent advances in the development of DCSCs for broader clinical applications will also be discussed, including DCSC composites, coated DCSC scaffolds and DCSC-coated metal implants.

Nobis, M, Herrmann, D, Warren, SC, Kadir, S, Leung, W, Killen, M, Magenau, A, Stevenson, D, Lucas, MC, Reischmann, N, Vennin, C, Conway, JRW, Boulghourjian, A, Zaratzian, A, Law, AM, Gallego-Ortega, D, Ormandy, CJ, Walters, SN, Grey, ST, Bailey, J, Chtanova, T, Quinn, JMW, Baldock, PA, Croucher, PI, Schwarz, JP, Mrowinska, A, Zhang, L, Herzog, H, Masedunskas, A, Hardeman, EC, Gunning, PW, del Monte-Nieto, G, Harvey, RP, Samuel, MS, Pajic, M, McGhee, EJ, Johnsson, A-KE, Sansom, OJ, Welch, HCE, Morton, JP, Strathdee, D, Anderson, KI & Timpson, P 2017, 'A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts', Cell Reports, vol. 21, no. 1, pp. 274-288.
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Oakes, SR, Gallego-Ortega, D, Stanford, PM, Junankar, S, Au, WWY, Kikhtyak, Z, von Korff, A, Sergio, CM, Law, AMK, Castillo, LE, Allerdice, SL, Young, AIJ, Piggin, C, Whittle, B, Bertram, E, Naylor, MJ, Roden, DL, Donovan, J, Korennykh, A, Goodnow, CC, O’Bryan, MK & Ormandy, CJ 2017, 'A mutation in the viral sensor 2’-5’-oligoadenylate synthetase 2 causes failure of lactation', PLOS Genetics, vol. 13, no. 11, pp. e1007072-e1007072.
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Peng, H, Lan, C, Zheng, Y, Hutvagner, G, Tao, D & Li, J 2017, 'Cross disease analysis of co-functional microRNA pairs on a reconstructed network of disease-gene-microRNA tripartite', BMC Bioinformatics, vol. 18, no. 1, pp. 1-17.
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© 2017 The Author(s). Background: MicroRNAs always function cooperatively in their regulation of gene expression. Dysfunctions of these co-functional microRNAs can play significant roles in disease development. We are interested in those multi-disease associated co-functional microRNAs that regulate their common dysfunctional target genes cooperatively in the development of multiple diseases. The research is potentially useful for human disease studies at the transcriptional level and for the study of multi-purpose microRNA therapeutics. Methods and results: We designed a computational method to detect multi-disease associated co-functional microRNA pairs and conducted cross disease analysis on a reconstructed disease-gene-microRNA (DGR) tripartite network. The construction of the DGR tripartite network is by the integration of newly predicted disease-microRNA associations with those relationships of diseases, microRNAs and genes maintained by existing databases. The prediction method uses a set of reliable negative samples of disease-microRNA association and a pre-computed kernel matrix instead of kernel functions. From this reconstructed DGR tripartite network, multi-disease associated co-functional microRNA pairs are detected together with their common dysfunctional target genes and ranked by a novel scoring method. We also conducted proof-of-concept case studies on cancer-related co-functional microRNA pairs as well as on non-cancer disease-related microRNA pairs. Conclusions: With the prioritization of the co-functional microRNAs that relate to a series of diseases, we found that the co-function phenomenon is not unusual. We also confirmed that the regulation of the microRNAs for the development of cancers is more complex and have more unique properties than those of non-cancer diseases.

Pham, HM, Nguyen, SC, Ho-Le, TP, Center, JR, Eisman, JA & Nguyen, TV 2017, 'Association of Muscle Weakness With Post-Fracture Mortality in Older Men and Women: A 25-Year Prospective Study', Journal of Bone and Mineral Research, vol. 32, no. 4, pp. 698-707.
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ABSTRACT   Osteoporotic fracture increases the risk of premature mortality. Muscle weakness is associated with both increased fracture risk and low bone mineral density (BMD). However, the role of muscle strength in post-fracture mortality is not well understood. This study examines the change of muscle strength measured at quadriceps (QS) before and after fracture and defines the relationship between muscle strength and post-fracture mortality. The study involved 889 women and 295 men (who were participating in the Dubbo Osteoporosis Study) who had at least one low-trauma fracture (ascertained from X-ray reports) after the age of 50 years. Median follow-up time was 11 years (range 1 to 24). To determine the change in muscle strength before and after a fracture, we selected a subset of 344 women and 99 men who had had at least two muscle strength measurements before the fracture event and a subset of 407 women and 105 men who had had at least two measurements after the fracture. During the follow-up period, 366 (41.2%) women and 150 (50.9%) men died. The annual rate of decrease in height-adjusted muscle strength before fracture was 0.27 kg/m (1.85%) in women and 0.40 kg/m (1.79%) in men. Strength loss after fracture was not significantly different from that before fracture. In women, after adjusting for baseline age and BMD, each SD (5 kg/m) lower height-adjusted pre- and post-fracture quadriceps strength was associated with a 27% (hazard ratio [HR] = 1.27; 95% confidence interval [CI] 1.07, 1.50) and 18% (HR = 1.18; 95% CI 1.01, 1.38) increase in post-fracture mortality risk, respectively. Similarly, in men, each SD (5 kg/m) lower height-adjusted pre- and post-fracture QS was associated with increased mortality before fracture (HR = 1.33; 95% CI 1.09, 1.63) and after fracture (HR = 1.43; 95% CI 1.16, 1.78). Muscle weakness accounted f...

Polonchuk, L, Chabria, M, Badi, L, Hoflack, J-C, Figtree, G, Davies, MJ & Gentile, C 2017, 'Cardiac spheroids as promising in vitro models to study the human heart microenvironment', Scientific Reports, vol. 7, no. 1, pp. 1-12.
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AbstractThree-dimensional in vitro cell systems are a promising alternative to animals to study cardiac biology and disease. We have generated three-dimensional in vitro models of the human heart (“cardiac spheroids”, CSs) by co-culturing human primary or iPSC-derived cardiomyocytes, endothelial cells and fibroblasts at ratios approximating those present in vivo. The cellular organisation, extracellular matrix and microvascular network mimic human heart tissue. These spheroids have been employed to investigate the dose-limiting cardiotoxicity of the common anti-cancer drug doxorubicin. Viability/cytotoxicity assays indicate dose-dependent cytotoxic effects, which are inhibited by the nitric oxide synthase (NOS) inhibitor L-NIO, and genetic inhibition of endothelial NOS, implicating peroxynitrous acid as a key damaging agent. These data indicate that CSs mimic important features of human heart morphology, biochemistry and pharmacology in vitro, offering a promising alternative to animals and standard cell cultures with regard to mechanistic insights and prediction of toxic effects in human heart tissue.

Popp, J, Matthews, D, Martinez-Coll, A, Mayerhöfer, T & Wilson, BC 2017, 'Challenges in translation: models to promote translation', Journal of Biomedical Optics, vol. 23, no. 02, pp. 1-1.
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We first discuss the main obstacles for clinical translation of biophotonics technologies, in particular, the different valleys of death, after which we present different examples of ways to bridge these gaps, remove the obstacles, and promote clinical translation.

Rafeie, M, Welleweerd, M, Hassanzadeh-Barforoushi, A, Asadnia, M, Olthuis, W & Ebrahimi Warkiani, M 2017, 'An easily fabricated three-dimensional threaded lemniscate-shaped micromixer for a wide range of flow rates', Biomicrofluidics, vol. 11, no. 1, pp. 014108-014108.
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Mixing fluid samples or reactants is a paramount function in the fields of micro total analysis system (μTAS) and microchemical processing. However, rapid and efficient fluid mixing is difficult to achieve inside microchannels because of the difficulty of diffusive mass transfer in the laminar regime of the typical microfluidic flows. It has been well recorded that the mixing efficiency can be boosted by migrating from two-dimensional (2D) to three-dimensional (3D) geometries. Although several 3D chaotic mixers have been designed, most of them offer a high mixing efficiency only in a very limited range of Reynolds numbers (Re). In this work, we developed a 3D fine-threaded lemniscate-shaped micromixer whose maximum numerical and empirical efficiency is around 97% and 93%, respectively, and maintains its high performance (i.e., &gt;90%) over a wide range of 1 &lt; Re &lt; 1000 which meets the requirements of both the μTAS and microchemical process applications. The 3D micromixer was designed based on two distinct mixing strategies, namely, the inducing of chaotic advection by the presence of Dean flow and diffusive mixing through thread-like grooves around the curved body of the mixers. First, a set of numerical simulations was performed to study the physics of the flow and to determine the essential geometrical parameters of the mixers. Second, a simple and cost-effective method was exploited to fabricate the convoluted structure of the micromixers through the removal of a 3D-printed wax structure from a block of cured polydimethylsiloxane. Finally, the fabricated mixers with different threads were tested using a fluorescent microscope demonstrating a good agreement with the results of the numerical simulation. We envisage that the strategy used in this work would expand the scope of the micromixer technology by broadening the range of efficient working flow rate and providing an easy way to the fabrication of 3D convoluted microstru...

Ramalingam, N, Warkiani, ME & Gong, TH-Q 2017, 'Acetylated bovine serum albumin differentially inhibits polymerase chain reaction in microdevices', Biomicrofluidics, vol. 11, no. 3, pp. 034110-034110.
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Bovine serum albumin (BSA) is widely used as an additive in polymerase chain reaction (PCR)-based microfluidic devices to passivate reactors and alleviate nucleic-acid amplification. BSA is available commercially in two types: either acetylated or non-acetylated. A survey of literature indicates that both types of BSA are used in PCR-based microfluidic devices. Our study results reveal that the use of acetylated BSA in PCR micro-devices leads to differential inhibition of PCR, compared to non-acetylated BSA. This result is noticed for the first time, and the differential inhibition generally goes un-noticed, as compared to complete PCR inhibition.

Rangel, L, Lospitao, E, Ruiz-Sáenz, A, Alonso, MA & Correas, I 2017, 'Alternative polyadenylation in a family of paralogousEPB41genes generates protein 4.1 diversity', RNA Biology, vol. 14, no. 2, pp. 236-244.
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Razmjou, A, Asadnia, M, Ghaebi, O, Yang, H-C, Ebrahimi Warkiani, M, Hou, J & Chen, V 2017, 'Preparation of Iridescent 2D Photonic Crystals by Using a Mussel-Inspired Spatial Patterning of ZIF-8 with Potential Applications in Optical Switch and Chemical Sensor', ACS Applied Materials & Interfaces, vol. 9, no. 43, pp. 38076-38080.
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© 2017 American Chemical Society. In this work, spatial patterning of a thin, dense, zeolitic imidazolate framework (ZIF-8) pattern was generated using photolithography and nanoscale (60 nm) dopamine coating. A bioinspired, unique, reversible, two-color iridescent pattern can be easily obtained for potential applications in sensing and photonics.

Salarnia, F 2017, 'Mutations in Hepatitis-B X-Gene Region: Chronic Hepatitis-B versus Cirrhosis', JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH, vol. 11, no. 3, pp. OC31-OC34.
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INTRODUCTION: Specific mutations in Hepatitis-B Virus (HBV) genome would proceed the development of chronic hepatitis B to more serious consequences like cirrhosis and end-stage liver disease. AIM: This study was designed to detect deletion and insertion mutational patterns in the X-gene region in a population of chronic HBV and related cirrhosis patients. MATERIALS AND METHODS: Sixty eight chronic HBV patients and 34 HBV-related cirrhotics were recruited from the eligible cases (N=50) referred to the academic hospitals of Gorgan city, Northeast of Iran, between Jan 2011 to Dec 2013. The HBx region was amplified by semi-nested PCR using serum samples and analyzed by sequencing. RESULTS: Our findings showed deletions and insertions in the C-terminal of HBx of the cirrhotic group and 8 bp found in two chronic HBV cases (2.9%). We detected 15 types of deletions in cirrhotic cases such as 1762-1768, 1763-1770, 1769-1773 and T1771/A1775. CONCLUSION: We found that the frequencies of deletion and insertion mutations in C-terminal of X-gene were more seen in cirrhotic patients comparing to chronic HBV cases in our area of study.

Sarkheil, H, Rahbari, S, Rad, MH & Tavakoli, J 2017, 'Development of a three-step hierarchical screening matrix to optimize inherently safety design index and inherently safety design cost (A case study in Acetic acid production process)', JOURNAL OF HEALTH AND SAFETY AT WORK, vol. 7, no. 3, pp. 245-254.

Schwarzer, A, Emmrich, S, Schmidt, F, Beck, D, Ng, M, Reimer, C, Adams, FF, Grasedieck, S, Witte, D, Käbler, S, Wong, JWH, Shah, A, Huang, Y, Jammal, R, Maroz, A, Jongen-Lavrencic, M, Schambach, A, Kuchenbauer, F, Pimanda, JE, Reinhardt, D, Heckl, D & Klusmann, J-H 2017, 'The non-coding RNA landscape of human hematopoiesis and leukemia', Nature Communications, vol. 8, no. 1, pp. 1-17.
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AbstractNon-coding RNAs have emerged as crucial regulators of gene expression and cell fate decisions. However, their expression patterns and regulatory functions during normal and malignant human hematopoiesis are incompletely understood. Here we present a comprehensive resource defining the non-coding RNA landscape of the human hematopoietic system. Based on highly specific non-coding RNA expression portraits per blood cell population, we identify unique fingerprint non-coding RNAs—such as LINC00173 in granulocytes—and assign these to critical regulatory circuits involved in blood homeostasis. Following the incorporation of acute myeloid leukemia samples into the landscape, we further uncover prognostically relevant non-coding RNA stem cell signatures shared between acute myeloid leukemia blasts and healthy hematopoietic stem cells. Our findings highlight the importance of the non-coding transcriptome in the formation and maintenance of the human blood hierarchy.

Sengupta, D, Kottapalli, AGP, Chen, SH, Miao, JM, Kwok, CY, Triantafyllou, MS, Warkiani, ME & Asadnia, M 2017, 'Characterization of single polyvinylidene fluoride (PVDF) nanofiber for flow sensing applications', AIP Advances, vol. 7, no. 10, pp. 105205-105205.
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The use of Polyvinylidene Fluoride (PVDF) based piezoelectric nanofibers for sensing and actuation has been reported widely in the past. However, in most cases, PVDF piezoelectric nanofiber mats have been used for sensing applications. This work fundamentally characterizes a single electrospun PVDF nanofiber and demonstrates its application as a sensing element for nanoelectromechanical sensors (NEMS). PVDF nanofiber mats were spun by far field electrospinning (FFES) process and complete material characterization was conducted by means of scanning electron microscope (SEM) imaging, Raman Spectroscopy and FTIR spectroscopy. An optimized recipe was developed for spinning a single suspended nanofiber on a specially designed MEMS substrate which allows the nano-mechanical and electrical characterization of a single PVDF nanofiber. Electrical characterization is conducted using a single suspended nanofiber to determine the piezoelectric coefficient (d33) of the nanofiber to be -58.77 pm/V. Also the mechanical characterization conducted using a nanoindenter revealed a Young’s Modulus and hardness of 2.2 GPa and 0.1 GPa respectively. Finally, an application that utilizes the single PVDF nanofiber as a sensing element to form a NEMS flow sensor is demonstrated. The single nanofiber flow sensor is tested in presence of various oscillatory flow conditions.

Shakeel Syed, M, Rafeie, M, Henderson, R, Vandamme, D, Asadnia, M & Ebrahimi Warkiani, M 2017, 'A 3D-printed mini-hydrocyclone for high throughput particle separation: application to primary harvesting of microalgae', Lab on a Chip, vol. 17, no. 14, pp. 2459-2469.
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3D-printed hydrocyclones are low-cost microdevices which be part of a library of standardized active and passive microfluidic components, suitable for particle–liquid separation.

Shirani, E, Razmjou, A, Tavassoli, H, Landarani-Isfahani, A, Rezaei, S, Abbasi Kajani, A, Asadnia, M, Hou, J & Ebrahimi Warkiani, M 2017, 'Strategically Designing a Pumpless Microfluidic Device on an “Inert” Polypropylene Substrate with Potential Application in Biosensing and Diagnostics', Langmuir, vol. 33, no. 22, pp. 5565-5576.
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© 2017 American Chemical Society. This study is an attempt to make a step forward to implement the very immature concept of pumpless transportation of liquid into a real miniaturized device or lab-on-chip (LOC) on a plastic substrate. 'Inert' plastic materials such as polypropylene (PP) are used in a variety of biomedical applications but their surface engineering is very challenging. Here, it was demonstrated that with a facile innovative wettability patterning route using fluorosilanized UV-independent TiO2 nanoparticle coating it is possible to create wedge-shaped open microfluidic tracks on inert solid surfaces for low-cost biomedical devices (lab-on-plastic). For the future miniaturization and integration of the tracks into a device, a variety of characterization techniques were used to not only systematically study the surface patterning chemistry and topography but also to have a clear knowledge of its biological interactions and performance. The effect of such surface architecture on the biological performance was studied in terms of static/dynamic protein (bovine serum albumin) adsorption, bacterial (Staphylococcus aureus and Staphylococcus epidermidis) adhesion, cell viability (using HeLa and MCF-7 cancer cell lines as well as noncancerous human fibroblast cells), and cell patterning (Murine embryonic fibroblasts). Strategies are discussed for incorporating such a confined track into a diagnostic device in which its sensing portion is based on protein, microorganism, or cells. Finally, for the proof-of-principle of biosensing application, the well-known high-affinity molecular couple of BSA-antiBSA as a biological model was employed.

Su, QP, Du, W, Ji, Q, Xue, B, Jiang, D, Zhu, Y, Ren, H, Zhang, C, Lou, J, Yu, L & Sun, Y 2017, 'Correction: Corrigendum: Vesicle Size Regulates Nanotube Formation in the Cell', Scientific Reports, vol. 7, no. 1, p. 40108.
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Scientific Reports 6: Article number: 24002; published online: 07 April 2016; updated: 09 February 2017 He Ren and Chuanmao Zhang were omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, as well as the Supplementary Information that now accompanies the Article.

T. Chorsi, H, Zhu, Y & Zhang, JXJ 2017, 'Patterned Plasmonic Surfaces—Theory, Fabrication, and Applications in Biosensing', Journal of Microelectromechanical Systems, vol. 26, no. 4, pp. 718-739.
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Low-profile patterned plasmonic surfaces are synergized with a broad class of silicon microstructures to greatly enhance near-field nanoscale imaging, sensing, and energy harvesting coupled with far-field free-space detection. This concept has a clear impact on several key areas of interest for the MEMS community, including but not limited to ultra-compact microsystems for sensitive detection of small number of target molecules, and 'surface' devices for optical data storage, micro-imaging and displaying. In this paper, we review the current state-of-the-art in plasmonic theory as well as derive design guidance for plasmonic integration with microsystems, fabrication techniques, and selected applications in biosensing, including refractive-index based label-free biosensing, plasmonic integrated lab-on-chip systems, plasmonic near-field scanning optical microscopy and plasmonics on-chip systems for cellular imaging. This paradigm enables low-profile conformal surfaces on microdevices, rather than bulk material or coatings, which provide clear advantages for physical, chemical and biological-related sensing, imaging, and light harvesting, in addition to easier realization, enhanced flexibility, and tunability.

Tavakoli, J 2017, 'Physico-mechanical, morphological and biomedical properties of a novel natural wound dressing material', Journal of the Mechanical Behavior of Biomedical Materials, vol. 65, pp. 373-382.
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Wound healing as a complex biological process greatly affects the quality of patients׳ lives. The high initial cost of wound treatment using advanced wound dressing is a major concern that warrants more attention. Because of the similarities between body macromolecules and polysaccharides and proteoglycans, gelatin and starch were used extensively as wound dressings; however their solubility in aqueous environment is known as a major drawback. Crosslinking, as a common method for enhancing mechanical properties, has its own limitation as some chemical cross-likers reduce biocompatibility. In this research, a simple and economical method for the fabrication of a novel wound dressing foam based on natural polymers of starch and gelatin with borax as the crosslinking agent is introduced. To evaluate the utility of the foams for wound dressing application, morphology, swelling behaviour and kinetics of swelling, vapour permeability, dimension stability, their mechanical properties and cytotoxicity as well as their ability to control release properties were examined as a function of crosslinking density. It was found that however, all borax-induced-samples show acceptable biocompatibility, incorporation of 30% borax solution optimises their mechanical properties.

Tavakoli, J 2017, 'Region–media coupling in characterization and modelling of the disc annulus single lamella swelling', Medical & Biological Engineering & Computing, vol. 55, no. 8, pp. 1483-1492.
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The annulus fibrosus (AF) swelling property, which is correlated with its rheological and viscoelastic properties, plays a significant role in disc nutrition and mechanical loading justification during daily activities as well as designing scaffolds for tissue engineering applications. The objective of this study was twofold: firstly to characterize the AF single lamella swelling kinetics in different regions and solutions at the temperature range of 35-40 °C and secondly to use the swelling results as a baseline to model (independent to swelling media and anatomic region) the AF single lamella swelling. It was found that the AF single lamella swelling kinetics (equilibrium swelling ratio and swelling rate) depends on anatomic region and swelling media; however, its trend for different swelling media (ionic and molecular solution) is similar and the majority of hydration occurs during first 20% of equilibrium swelling time (about 20 min). Change in swelling rate constant in circumferential direction depends on the solution type. It decreases from anterior to lateral regions for water, PBS and glucose solution and remains constant-or its change is negligible-from lateral to posterolateral regions. The effect of temperature (in the range of 35-40 °C) on swelling kinetics was seen to be negligible. It was also understood that it is possible to present a model (independent to swelling media type) to predict the swelling kinetics of posterior and posterolateral AF single lamella, as these locations are less sensitive to the swelling media.

Tavakoli, J 2017, 'Tissue Engineering of the Intervertebral Disc’s Annulus Fibrosus: A Scaffold-Based Review Study', Tissue Engineering and Regenerative Medicine, vol. 14, no. 2, pp. 81-91.
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Tissue engineering as a high technology solution for treating disc's problem has been the focus of some researches recently; however, the upcoming successful results in this area depends on understanding the complexities of biology and engineering interface. Whereas the major responsibility of the nucleus pulposus is to provide a sustainable hydrated environment within the disc, the function of the annulus fibrosus (AF) is more mechanical, facilitating joint mobility and preventing radial bulging by confining of the central part, which makes the AF reconstruction important. Although the body of knowledge regarding the AF tissue engineering has grown rapidly, the opportunities to improve current understanding of how artificial scaffolds are able to mimic the AF concentric structure-including inter-lamellar matrix and cross-bridges-addressed unresolved research questions. The aim of this literature review was to collect and discuss, from the international scientific literature, information about tissue engineering of the AF based on scaffold fabrication and material properties, useful for developing new strategies in disc tissue engineering. The key parameter of this research was understanding if role of cross-bridges and inter-lamellar matrix has been considered on tissue engineering of the AF.

Tavakoli, J & Costi, JJ 2017, 'Development of a rapid matrix digestion technique for ultrastructural analysis of elastic fibers in the intervertebral disc', Journal of the Mechanical Behavior of Biomedical Materials, vol. 71, pp. 175-183.
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Collagen and elastic fibers are two major fibrous constituents of the annulus fibrosus (AF) in the disc that contribute to its mechanical and viscoelastic properties. It was thought that elastic fibers play no substantial role in the function and properties of the disc as these fibers were irregularly distributed. Studies that have revealed highly organized elastic fibers with different regional orientation and distribution, while being strongly crosslinked with matrix, suggesting their contribution to disc structure-function properties. These studies that were performed by light microscopic analysis of histologically prepared samples, have not been able to reveal the fine-scale architectural details of the elastic fiber network. Since elastic fibers are intermingled with other fibrous components of the disc and mostly obscured by the extracellular matrix, it is difficult to demonstrate their ultra-structural organization using scanning electron microscopy (SEM). Therefore the aim of this study was to develop a rapid matrix digestion technique for ultrastructural analysis of the disc elastic fibers. This study provides a new method for fundamental visualization of elastic fibers and their architecture in the disc. Through the ultra-structural analysis, the relationship between structure and function, as well as the role of elastic fibers on AF mechanical properties can be studied. This method may be used to develop a three-dimensional map of elastic fibers distribution within the disc, which would provide valuable information for designing tissue engineered scaffolds for AF repair and replacement.

Tavakoli, J & Tang, Y 2017, 'Honey/PVA hybrid wound dressings with controlled release of antibiotics: Structural, physico-mechanical and in-vitro biomedical studies', Materials Science and Engineering: C, vol. 77, pp. 318-325.
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Hydrogel/honey hybrids manifest an attractive design with an exclusive therapeutic property that promotes wound healing process. The greater the concentration of honey within the formulation, the better the biomedical properties that will be achieved. However, an increase in the percentage of honey can negatively affect the physico-chemical and mechanical properties of hybrid hydrogels. The need exists, therefore, to prepare wound dressings that contain high honey density with optimal biomedical, mechanical and physicochemical properties. In this study, a simple method for the preparation of a highly concentrated honey/PVA hybrid hydrogel with borax as the crosslinking agent is reported. Comprehensive evaluations of the morphology, swelling kinetics, permeability, bio-adhesion, mechanical characteristics, cytotoxicity, antibacterial property, cell proliferation ability and their controlling release properties were conducted as a function of crosslinking density. All the borax-induced hydrogels showed acceptable biocompatibility, and the incorporation of 1% borax in the hydrogel formulation produced optimal behaviours for wound addressing applications.

Tavakoli, J & Tang, Y 2017, 'Hydrogel Based Sensors for Biomedical Applications: An Updated Review', Polymers, vol. 9, no. 12, pp. 364-364.
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Biosensors that detect and convert biological reactions to a measurable signal have gained much attention in recent years. Between 1950 and 2017, more than 150,000 papers have been published addressing the applications of biosensors in different industries, but to the best of our knowledge and through careful screening, critical reviews that describe hydrogel based biosensors for biomedical applications are rare. This review discusses the biomedical application of hydrogel based biosensors, based on a search performed through Web of Science Core, PubMed (NLM), and Science Direct online databases for the years 2000⁻2017. In this review, we consider bioreceptors to be immobilized on hydrogel based biosensors, their advantages and disadvantages, and immobilization techniques. We identify the hydrogels that are most favored for this type of biosensor, as well as the predominant transduction strategies. We explain biomedical applications of hydrogel based biosensors including cell metabolite and pathogen detection, tissue engineering, wound healing, and cancer monitoring, and strategies for small biomolecules such as glucose, lactate, urea, and cholesterol detection are identified.

Tavakoli, J, Elliott, DM & Costi, JJ 2017, 'The ultra-structural organization of the elastic network in the intra- and inter-lamellar matrix of the intervertebral disc', Acta Biomaterialia, vol. 58, pp. 269-277.
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The inter-lamellar matrix (ILM)-located between adjacent lamellae of the annulus fibrosus-consists of a complex structure of elastic fibers, while elastic fibers of the intra-lamellar region are aligned predominantly parallel to the collagen fibers. The organization of elastic fibers under low magnification, in both inter- and intra-lamellar regions, was studied by light microscopic analysis of histologically prepared samples; however, little is known about their ultrastructure. An ultrastructural visualization of elastic fibers in the inter-lamellar matrix is crucial for describing their contribution to structural integrity, as well as mechanical properties of the annulus fibrosus. The aims of this study were twofold: first, to present an ultrastructural analysis of the elastic fiber network in the ILM and intra-lamellar region, including cross section (CS) and in-plane (IP) lamellae, of the AF using Scanning Electron Microscopy (SEM) and second, to -compare the elastic fiber orientation between the ILM and intra-lamellar region. Four samples (lumbar sheep discs) from adjacent sections (30μm thickness) of anterior annulus were partially digested by a developed NaOH-sonication method for visualization of elastic fibers by SEM. Elastic fiber orientation and distribution were quantified relative to the tangential to circumferential reference axis. Visualization of the ILM under high magnification revealed a dense network of elastic fibers that has not been previously described. Within the ILM, elastic fibers form a complex network, consisting of different size and shape fibers, which differed to those located in the intra-lamellar region. For both regions, the majority of fibers were oriented near 0° with respect to tangential to circumferential (TCD) direction and two minor symmetrical orientations of approximately±45°. Statistically, the orientation of elastic fibers between the ILM and intra-lamellar region was not different (p=0.171). The present stud...

Thach, T, Bliuc, D, Hanh, P, van Geel, T, Adachi, JD, Berger, C, van den Bergh, J, Eisman, JA, Geusens, P, Goltzman, D, Hanley, DA, Josse, RG, Kaiser, SM, Kovacs, CS, Langsetmo, L, Prior, JC, Nguyen, TV & Center, JR 2017, 'Transition to re-fracture and mortality in the elderly: An individualized risk assessment tool for fracture and its outcomes from two large population-based prospective cohort studies.', JOURNAL OF BONE AND MINERAL RESEARCH, vol. 32, pp. S19-S19.

Ting, SRS, Min, EH, Lau, BKF & Hutvagner, G 2017, 'Acetyl‐α‐d‐mannopyranose‐based cationic polymer via RAFT polymerization for lectin and nucleic acid bindings', Journal of Applied Polymer Science, vol. 134, no. 24, pp. 1-11.
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ABSTRACTFunctional cationic polymers carrying mannose moieties were synthesized in a facile manner by employing RAFT polymerization. Initially, a protected carbohydrate based monomer, [2‐(2,3,4,6‐tetra‐O‐acetyl‐α‐d‐mannopyranosyloxy)ethyl methacrylate (AcManEMA)], was prepared by the O‐glycosylation of 2‐hydroxyethyl methacrylate (HEMA). Subsequently, a macroRAFT agent of poly[2‐(dimethyl)amino ethyl methacrylate] (PDMAEMA) was generated, and a further chain extension polymerization with AcManEMA was carried out in dioxane to form a acetylated mannose cationic diblock copolymer, PDMAEMA‐b‐PAcManEMA. It was attained in high yields and displayed low dispersity (Ð). Acetylated mannose moieties on the polymer were deprotected with sodium methoxide and the amines from the DMAEMA block were protonated to yield a cationic diblock glycopolymer, PDMAEMA‐b‐PManEMA. The cationic property of polymers were characterized by mixing with a negatively charged siRNA duplex and a pDNA, and aggregates of 102 and 233 nm were obtained, respectively. Agarose gel shift assay revealed that the polymers were able to retain the nucleic acids as large polymer complexes. Lectin binding assay proved that the mannose residue on the polymers were only able to bind specifically with ConA. PNA lectin was employed as a control and did not show specific binding. The cationic glycopolymer could be advantageous in targeted nucleic acids delivery in specific cells. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44947.

Tran, GM, Ho-Le, TP, Ha, DT, Tran-Nguyen, CH, Nguyen, TSM, Pham, TTN, Nguyen, TA, Nguyen, DA, Hoang, HQ, Tran, NV & Nguyen, TV 2017, 'Patterns of antimicrobial resistance in intensive care unit patients: a study in Vietnam', BMC Infectious Diseases, vol. 17, no. 1, pp. 1-7.
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© The Author(s). 2017. Background: Antimicrobial resistance has emerged as a major concern in developing countries. The present study sought to define the pattern of antimicrobial resistance in ICU patients with ventilator-associated pneumonia. Methods: Between November 2014 and September 2015, we enrolled 220 patients (average age ~ 71 yr) who were admitted to ICU in a major tertiary hospital in Ho Chi Minh City, Vietnam. Data concerning demographic characteristics and clinical history were collected from each patient. The Bauer-Kirby disk diffusion method was used to detect the antimicrobial susceptibility. Results: Antimicrobial resistance was commonly found in ceftriaxone (88%), ceftazidime (80%), ciprofloxacin (77%), cefepime (75%), levofloxacin (72%). Overall, the rate of antimicrobial resistance to any drug was 93% (n = 153/164), with the majority (87%) being resistant to at least 2 drugs. The three commonly isolated microorganisms were Acinetobacter (n = 75), Klebsiella (n = 39), and Pseudomonas aeruginosa (n = 29). Acinetobacter baumannii were virtually resistant to ceftazidime, ceftriaxone, piperacilin, imipenem, meropenem, ertapenem, ciprofloxacin and levofloxacin. High rates ( > 70%) of ceftriaxone and ceftazidime-resistant Klebsiella were also observed. Conclusion: These data indicated that critically ill patients on ventilator in Vietnam were at disturbingly high risk of antimicrobial resistance. The data also imply that these Acinetobacter, Klebsiella, and Pseudomonas aeruginosa and multidrug resistance pose serious therapeutic problems in ICU patients. A concerted and systematic effort is required to rapidly identify high risk patients and to reduce the burden of antimicrobial resistance in developing countries.

Tran, T, Bliuc, D, van Geel, T, Adachi, JD, Berger, C, van den Bergh, J, Eisman, JA, Geusens, P, Goltzman, D, Hanley, DA, Josse, RG, Kaiser, SM, Kovacs, CS, Langsetmo, L, Prior, JC, Nguyen, TV & Center, JR 2017, 'Population-Wide Impact of Non-Hip Non-Vertebral Fractures on Mortality', Journal of Bone and Mineral Research, vol. 32, no. 9, pp. 1802-1810.
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ABSTRACT   Data on long-term consequences of non-hip non-vertebral (NHNV) fractures, accounting for approximately two-thirds of all fragility fractures, are scanty. Our study aimed to quantify the population-wide impact of NHNV fractures on mortality. The national population-based prospective cohort study (Canadian Multicentre Osteoporosis Study) included 5526 community dwelling women and 2163 men aged 50 years or older followed from July 1995 to September 2013. Population impact number was used to quantify the average number of people for whom one death would be attributable to fracture and case impact number to quantify the number of deaths out of which one would be attributable to a fracture. There were 1370 fragility fractures followed by 296 deaths in women (mortality rate: 3.49; 95% CI, 3.11 to 3.91), and 302 fractures with 92 deaths in men (5.05; 95% CI, 4.12 to 6.20). NHNV fractures accounted for three-quarters of fractures. In women, the population-wide impact of NHNV fractures on mortality was greater than that of hip and vertebral fractures because of the greater number of NHNV fractures. Out of 800 women, one death was estimated to be attributable to a NHNV fracture, compared with one death in 2000 women attributable to hip or vertebral fracture. Similarly, out of 15 deaths in women, one was estimated to be attributable to a NHNV fracture, compared with one in over 40 deaths for hip or vertebral fracture. The impact of forearm fractures (ie, one death in 2400 women and one out of 42 deaths in women attributable to forearm fracture) was similar to that of hip, vertebral, or rib fractures. Similar, albeit not significant, results were noted for men. The study highlights the important contribution of NHNV fractures on mortality because many NHNV fracture types, except for the most distal fractures, have serious adverse consequ...

Valdés-Mora, F, Gould, CM, Colino-Sanguino, Y, Qu, W, Song, JZ, Taylor, KM, Buske, FA, Statham, AL, Nair, SS, Armstrong, NJ, Kench, JG, Lee, KML, Horvath, LG, Qiu, M, Ilinykh, A, Yeo-Teh, NS, Gallego-Ortega, D, Stirzaker, C & Clark, SJ 2017, 'Acetylated histone variant H2A.Z is involved in the activation of neo-enhancers in prostate cancer', Nature Communications, vol. 8, no. 1.
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AbstractAcetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers. H2A.Zac nucleosome occupancy is rapidly remodeled to flank the AR sites to initiate the formation of nucleosome-free regions and the production of AR-enhancer RNAs upon androgen treatment. Remarkably higher levels of global H2A.Zac correlate with poorer prognosis. Altogether these data demonstrate the novel contribution of H2A.Zac in activation of newly formed enhancers in prostate cancer.

Valdés-Mora, F, Locke, WJ, Bandrés, E, Gallego-Ortega, D, Cejas, P, García-Cabezas, MA, Colino-Sanguino, Y, Feliú, J, del Pulgar, TG & Lacal, JC 2017, 'Clinical relevance of the transcriptional signature regulated by CDC42 in colorectal cancer', Oncotarget, vol. 8, no. 16, pp. 26755-26770.
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Vennin, C, Chin, VT, Warren, SC, Lucas, MC, Herrmann, D, Magenau, A, Melenec, P, Walters, SN, del Monte-Nieto, G, Conway, JRW, Nobis, M, Allam, AH, McCloy, RA, Currey, N, Pinese, M, Boulghourjian, A, Zaratzian, A, Adam, AAS, Heu, C, Nagrial, AM, Chou, A, Steinmann, A, Drury, A, Froio, D, Giry-Laterriere, M, Harris, NLE, Phan, T, Jain, R, Weninger, W, McGhee, EJ, Whan, R, Johns, AL, Samra, JS, Chantrill, L, Gill, AJ, Kohonen-Corish, M, Harvey, RP, Biankin, AV, Evans, TRJ, Anderson, KI, Grey, ST, Ormandy, CJ, Gallego-Ortega, D, Wang, Y, Samuel, MS, Sansom, OJ, Burgess, A, Cox, TR, Morton, JP, Pajic, M & Timpson, P 2017, 'Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis', Science Translational Medicine, vol. 9, no. 384.
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Fine-tuned manipulation of tumor tension and vasculature enhances response to chemotherapy and impairs metastatic spread in pancreatic cancer.

Viglione, LL, Chamoli, U & Diwan, AD 2017, 'Is Stand-Alone Anterior Lumbar Interbody Fusion a Safe and Efficacious Treatment for Isthmic Spondylolisthesis of L5-S1?', Global Spine Journal, vol. 7, no. 6, pp. 587-595.
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Study Design:A systematic review.Objective:The objective of this study was to determine the safety and efficacy of stand-alone anterior lumbar interbody fusion (sa-ALIF) for the treatment of symptomatic isthmic spondylolisthesis of L5-S1 by assessing the level of available clinical and radiographic evidence.Methods:A systematic review utilizing Medline, Embase, and Scopus online databases was undertaken. Clinical, radiographic, and adverse outcome data were extracted for the relevant isthmic spondylolisthesis cases with the intention of undertaking a meta-analysis.Results:The database search between January 1980 and December 2015 yielded 23 articles that concerned sa-ALIF for isthmic spondylolisthesis of L5-S1. Only in 9 of the 23 articles data could be extracted specific to sa-ALIF for isthmic spondylolisthesis of L5-S1. There was considerable inconsistency in the standards for reporting outcomes of the surgery due to which meta-analysis could not be undertaken, and hence each article was reviewed.Conclusions:There was insufficient evidence to support the safety and efficacy of sa-ALIF for the treatment of isthmic spondylolisthesis of L5-S1. Although sa-ALIF is widely documented in the literature, there was insufficient evidence to support its use in treating this specific pathology. The unique pathological and anatomical situation that isthmic spondylolisthesis of L5-S1 presents must be recognized and its treatment with sa-ALIF should be well thought out.

Wang, L, Ren, L, Mitchell, D, Casillas-Garcia, G, Ren, W, Ma, C, Xu, XX, Wen, S, Wang, F, Zhou, J, Xu, X, Hao, W, Dou, SX & Du, Y 2017, 'Enhanced energy transfer in heterogeneous nanocrystals for near infrared upconversion photocurrent generation', Nanoscale, vol. 9, no. 47, pp. 18661-18667.
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A heterogeneous NaYF₄:Yb,Tm@ZnO nanoparticle with an epitaxial interface is prepared, and it possesses an enhanced upconversion emission intensity and an excellent photocurrent response.

Wang, L, Yang, Q, Chen, Y, Chai, Y, Li, JJ, Du, L, Tan, R, Yang, S, Tu, M & Yu, B 2017, 'A reformative shear precipitation procedure for the fabrication of vancomycin-loaded poly(lactide-co-glycolide) microspheres', Journal of Biomaterials Applications, vol. 31, no. 7, pp. 995-1009.
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This study reports the encapsulation of vancomycin, as a model hydrophilic drug, into poly(lactide-co-glycolide) microspheres using a novel reformative shear precipitation procedure. In contrast to the external aqueous phase used in the conventional microencapsulation technique based on emulsion solvent evaporation/extraction, the reformative shear precipitation procedure explored in this study uses a shear medium composed of glycerol as the viscous medium and ethanol as polymer antisolvent, which is relatively immiscible with the hydrophilic drug. This limits drug diffusion and leads to rapid microsphere solidification, which allows a large proportion of the hydrophilic drug to be encapsulated within the microspheres. The influence of various processing parameters, including polymer concentration, volume ratio of ethanol to glycerol in the shear medium, volume of aqueous drug solution, initial drug loading, and injecting rate of the drug–polymer emulsion, on the encapsulation efficiency and characteristics of resulting microspheres were investigated. The morphology and release characteristics, as well as mechanical, in vitro and in vivo behaviour of vancomycin-loaded poly(lactide-co-glycolide) microspheres prepared using the novel procedure were also investigated. The results demonstrated that the reformative shear precipitation procedure could achieve the loading of hydrophilic drugs into poly(lactide-co-glycolide) microspheres with high encapsulation efficiency, and the success of the procedure was largely influenced by the volume ratio of ethanol to glycerol in the shear medium. Vancomycin-loaded poly(lactide-co-glycolide) microspheres prepared using this procedure demonstrated favourable mechanical characteristics, antibacterial activity, and in vivo degradation behaviour which suggested their suitability for use as a sustained delivery system.

Xu, X, Clarke, C, Ma, C, Casillas, G, Das, M, Guan, M, Liu, D, Wang, L, Tadich, A, Du, Y, Ton-That, C & Jin, D 2017, 'Depth-profiling of Yb³⁺ sensitizer ions in NaYF₄ upconversion nanoparticles', Nanoscale, vol. 9, no. 23, pp. 7719-7726.
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© 2017 The Royal Society of Chemistry. Enhancing the efficiency of upconversion nanoparticles (UCNPs) and therefore their brightness is the critical goal for this emerging material to meet growing demands in many potential applications including sensing, imaging, solar energy conversion and photonics. The distribution of the photon sensitizer and activator ions that form a network of energy transfer systems within each single UCNP is vital for understanding and optimizing their optical properties. Here we employ synchrotron-based X-ray Photoelectron Spectroscopy (XPS) to characterize the depth distribution of Yb3+ sensitizer ions in host NaYF4 nanoparticles and systematically correlate the structure with the optical properties for a range of UCNPs with different sizes and doping concentrations. We find a radial gradient distribution of Yb3+ from the core to the surface of the NaYF4 nanoparticles, regardless of their size or the sensitizer's concentration. Energy dispersive X-ray Spectroscopy (EDX) was also used to further confirm the distribution of the sensitizer ions in the host matrix. These results have profound implications for the upconversion optical property variations.

Zhand, S, Bazuori, M, Tabarraei, A & Moradi, A 2017, 'Molecular Epidemiology of Hepatitis C Virus Genotypes in Patients with Thalassemia Major in Golestan Province, Iran', Journal of Clinical and Basic Research, vol. 1, no. 1, pp. 1-10.
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Introduction: In Iran, hepatitis C virus (HCV) is the most prevalent cause of chronic hepatitis and cirrhosis in patients with hemophilia, thalassemia, and renal failure. Recent studies suggest that patients infected with different HCV genotypes have different clinical profiles, severity of liver disease and response to therapy. Several molecular methods targeting different HCV genomic regions have been introduced for genotyping. Direct sequencing of amplified PCR products is the gold standard method, followed by phylogenetic analysis of clinical material. The aim of this study was to determine genotypes of HCV-infected patients with thalassemia in Golestan Province, Iran. Materials and Methods: This cross-sectional study included 217 patients (mean age: 21.82 ± 16 years, 50.7% male) with thalassemia major. Enzyme-linked immunosorbent assay (ELISA) was used for detection of HCV antibodies. Positive HCV-Ab samples were confirmed by reverse transcription polymerase chain reaction (RT-PCR) and sequencing. HCV genotypes were determined by aligning nucleotide sequences of patients with the standard nucleotide sequences obtained from GenBank (accession number: AB520610). Results: Of 217 patients with thalassemia major, 14 (6.45%) were found as anti-HCV-positive in the ELISA test. Among them, two patients (14.28%) had positive RT-PCR results. In addition, all patients were infected with HCV genotype 1a. Conclusions: Genotype 1a is the predominant HCV genotype in patients with thalassemia major in the Golestan province, Iran.

Zhand, S, Hoseini, SM, Tabarraei, A, Saeedi, M & Moradi, A 2017, 'Study of the transcript and protein expression of poliovirus receptor (CD155 protein) on colorectal cancer cell line', Journal of Isfahan Medical School, vol. 35, no. 427, pp. 453-462.
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Background: Poliovirus receptor (CD155 protein or PVR) expressed on many types of cells and exerts diverse functions. Several studies have demonstrated that changes in CD155 expression in cancer cell lines affect metastasis, proliferation, and migration. The purpose of the present study was to investigate the transcript and protein expression of CD155 in human colon adenocarcinoma cell lines in comparison to normal fetal human colon (FHC) cells. Methods: The CD155 expression levels in a human adenocarcinoma cell line and normal colon cell line were evaluated using the quantitative real-time polymerase chain reaction (PCR) and flow cytometry. All statistical analyses were performed using SPSS software at the statistical significance level of P < 0.050. Findings: Real-time polymerase chain reaction indicated that CD155 significantly overexpressed in human adenocarcinoma cell line significantly more than normal fetal cells (P < 0.001). Flow cytometry showed that protein was strongly expressed in cancer cell line and SW480 cell line showed the highest CD155 protein expression level of 98.0%, whereas this protein expression was 1.3% in human normal colon cell line (P < 0.001). Conclusion: Collectively, these data indicate that CD155 expression is frequently elevated in cancer cell line. The preferential expression of CD155 on cancer cell line rather than on normal cell line suggests that CD155 could be targeted for future poliovirus virotherapy.

Zhand, S, Tabarraei, A, Nazari, A & Moradi, A 2017, 'Cytotoxic T lymphocytes and CD4 epitope mutations in the pre-core/core region of hepatitis B virus in chronic hepatitis B carriers in Northeast Iran', Indian Journal of Gastroenterology, vol. 36, no. 4, pp. 253-257.
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BACKGROUNDS: Hepatitis B virus (HBV) is vulnerable to many various mutations. Those within epitopes recognized by sensitized T cells may influence the re-emergence of the virus. This study was designed to investigate the mutation in immune epitope regions of HBV pre-core/core among chronic HBV patients of Golestan province, Northeast Iran. METHODS: In 120 chronic HBV carriers, HBV DNA was extracted from blood plasma samples and PCR was done using specific primers. Direct sequencing and alignment of the pre-core/core region were applied using reference sequence from Gene Bank database (Accession Number AB033559). RESULTS: The study showed 27 inferred amino acid substitutions, 9 of which (33.3%) were in CD4 and 2 (7.4%) in cytotoxic T lymphocytes' (CTL) epitopes and 16 other mutations (59.2%) were observed in other regions. CONCLUSIONS: CTL escape mutations were not commonly observed in pre-core/core sequences of chronic HBV carriers in the locale of study. It can be concluded that most of the inferred amino acid substitutions occur in different immune epitopes other than CTL and CD4.

Alzahid, Y, Mostaghimi, P, Warkiani, ME, Armstrong, RT, Joekar-Niasar, V & Karadimitriou, N 1970, 'Alkaline Surfactant Polymer Flooding: What Happens at the Pore Scale?', Day 2 Tue, June 13, 2017, SPE Europec featured at 79th EAGE Conference and Exhibition, SPE, pp. 386-402.
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Abstract Alkaline-surfactant-polymer (ASP) flooding is a Chemical Enhanced Oil Recovery (CEOR) method whereby alkali, surfactant and polymer are injected as the same slug. It is one of the most promising world-wide focus of CEOR research and field trials, due to the unique synergy of the three chemical components. Polymers increase the viscosity of injected water, which improves macroscopic sweep efficiency by stabilizing the displacing front and counteracting heterogeneity effects. Surfactants, on the other hand, decrease the interfacial tension between the injected water and crude oil, which improves microscopic displacement efficiency by mobilizing trapped oil. Alkaline chemicals generate soap when reacting with crude oil, which reduces surfactant adsorption to grain surfaces. To fully understand the flow mechanisms in oil reservoirs and develop efficient recovery methods, it is essential to recognize the physics at the pore scale since this is the length scale at which capillary-trapped oil is mobilized. We developed an experimental micro-scale approach in which oil recovery is analyzed using microfluidics. The micromodels are fabricated based on: (1) a pore network generated via a Delaunay triangulation with an average pore size of 60 µm, (2) X-ray micro-Computed Tomography images of Bentheimer sandstone with resolution of 4.95 µm, and (3) a fractured network with a porosity of 10%. The networks are etched into silicon wafers and used to fabricate polydimethylsiloxane (PDMS) microfluidic devices. We compare not only oil recovery with ASP flooding between different porous networks but we also study displacement mechanisms and pore scale emulsion formation for ASP formulations that exhibit Winsor Type II+, II- and III behaviour. Our studies elucidate micro-scale oil recovery mechanisms for different ASP flooding scenarios. Our results provide direct visualization of the micro-scale phenomena occurring d...

Asadnia, M, Kottapalli, AGP, Warkiani, ME, Miao, JM & Triantafyllou, MS 1970, 'Engineering miniaturized hair cell sensors for auditory system', 2017 IEEE 30th International Conference on Micro Electro Mechanical Systems (MEMS), 2017 IEEE 30th International Conference on Micro Electro Mechanical Systems (MEMS), IEEE, Las Vegas, NV, pp. 1173-1176.
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© 2017 IEEE. Mechanosensory haircells are well-evolved biological sensors found in nature. In this paper, we present a novel artificial NEMS stereovilli sensor developed through novel fabrication techniques. The NEMS stereovilli sensor fabrication combines soft-polymer material synthesis methods and nanofiber generation techniques with conventional microfabrication methods to form novel flow sensors. The sensor fabrication mainly consists of three major steps which are 1) fabrication of artificial stereovilli of varying aspect ratios, 2) formation of nanofiber tip-links through electrospinning of PVDF material and 3) development of biomimetic HA-MA hydrogel cupula. These artificial sensors closely mimic stereovilli and achieve ultrahigh sensitivities through a biomimetic design. The sensors achieve a sensitivity and threshold detection limit of 300 mV/(m/s) and 8 μm/s, respectively.

Bliuc, D, Tran, T, van Geel, T, Adachi, J, Berger, C, van den Bergh, J, Eisman, JA, Geusens, P, Goltzman, D, Hanley, DA, Josse, RG, Kaiser, SM, Kovacs, CS, Langsetmo, L, Prior, JC, Nguyen, TV & Center, JR 1970, 'The Effect of Bisphosphonates on Mortality Risk Reduction is Partly Mediated Through a Reduction in the Rate of Bone Loss.', JOURNAL OF BONE AND MINERAL RESEARCH, Annual Meeting of the American-Society-for-Bone-and-Mineral-Research (ASBMR), WILEY, Denver, CO, pp. S23-S24.

Ghorbani, S, Razavi Bazaz, S, Ebrahimi Warkiani, M, Soleimani, M & Abouei Mehrizi, A 1970, 'Evaluation of Nanofiber PLA Scaffolds Using Dry-and Wet-Electro Spinning Methods', 2017 24th National and 2nd International Iranian Conference on Biomedical Engineering (ICBME), 2017 24th National and 2nd International Iranian Conference on Biomedical Engineering (ICBME), IEEE, Tehran, IRAN, pp. 89-94.
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© 2017 IEEE. Investigating the fabrication of a favorable scaffold is a continuing sconcern and an essential step within tissue engineering. An ideal scaffold should mimic the structure of extracellular matrix (ECM) which has considerable impacts on its function. To meet this demands, in this study, three-dimensional scaffolds by polylactic acid (PLA) polymer 10%, 13%, 15%, 17% and 20% (w/v) with a novel architecture produced by a wet-electrospinning process have been fabricated and compared with dry-electrospun scaffolds that have been developed for tissue engineering applications. In the wet-electrospinning method, an aqueous solution of sodium hydroxide (NaOH) (pH∼13) has been used as the coagulation bath instead of the aluminum collector which is used in the dry method. Comparing with usual nanofiber non-woven PLA fabric prepared by a conventional electrospinning method, wet-electrospun spongiform PLA nanofiber scaffolds have low apparent density and high porosity. The porosity of the scaffolds has been examined in this two methods and their mechanical properties as well as their morphology are investigated. All in all, it is shown that the novel nanofiber fabrication system would be amazingly useful for the structure control of the nanofiber fabric.

Hadgraft, RG, Francis, B, Lawson, J, Jarman, R, Stewart, C, Hsieh, I & Jenkins, G 1970, 'Curriculum transformation with students as partners', Proceedings of the 28th Annual Conference of the Australasian Association for Engineering Education (AAEE 2017), Annual Conference of the Australasian Association for Engineering, Australasian Association for Engineering Education, Manly, Australia, pp. 1-9.
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8732142. That was my student ID as an undergraduate (now one of the authors).It was a number, not a name. It distinguished students from professors and all other teachingstaff and, in a symbolic way, reminded us all of our firm place as students, as learners. Therewas a big power differential between students and teachers in the 1980s. What we learnedwas prescribed, transmitted and tested in implicit ways (no rubrics or marking criteria in thosedays) and rarely were our skills tested – just what we knew and could recall at a given time.Sometimes people say that teaching is an act. Indeed, sage on the stage suggests thisprecisely. But being a student is also an act. Students also assume roles and personas.If we want curriculum transformation, we seek to put a stop to acting – to engage studentsand staff in authentic learning.MIDAS is our curriculum transformation project in the Faculty of Engineering and InformationTechnology (FEIT) at UTS – More Innovative Design-Able Students. In MIDAS, we wantstudents and teachers to be their authentic selves in a true teaching and learningpartnership. MIDAS seeks mutual respect in people, not the fulfilment of roles.MIDAS doesn’t see students as numbers, but as partners, as people who can learn,contribute, inspire, teach and create … and it sees teachers as people who also learn,contribute, inspire, teach and create

Herrmann, D, Erami, Z, Warren, S, Nobis, M, Magenau, A, Lucas, M, Vennin, C, McGhee, EJ, Leung, W, Reischmann, N, Mrowinska, A, Schwarz, JP, Kadir, S, Karim, SA, Campbell, AD, Gallego-Ortega, D, Evans, J, Sansom, OJ, Morton, JP, Anderson, KI & Timpson, P 1970, 'Abstract PR07: A biosensor mouse to predict the dissociation and spread of pancreatic cancer', Cancer Research, Abstracts: AACR Special Conference: Engineering and Physical Sciences in Oncology; June 25-28, 2016; Boston, MA, American Association for Cancer Research (AACR), Boston, MA, pp. PR07-PR07.
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Abstract E-cadherin-mediated cell-cell junctions play a physical role in maintaining normal epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here, we have generated an E-cadherin-GFP(FRAP) biosensor mouse, which enables intravital photobleaching and quantification of E-cadherin mobility in live tissue, without affecting normal biology. We demonstrate using FRAP or FLIP, the broad applications of this mouse to examine E-cadherin regulation in multiple tissues including mammary, brain, liver and kidney, while specifically monitoring E-cadherin mobility during disease progression in the pancreas. We assess E-cadherin stability in native pancreatic tissue, upon genetic manipulation involving Kras and p53 or in response to anti-invasive drug treatment, and reveal new insights into the dynamic remodeling of E-cadherin during in situ cancer progression. Photobleaching in the E-cadherin-GFP(FRAP) mouse correlate directly with epithelial integrity and mechanical strength making the biosensor mouse a valuable tool to fundamentally expand our understanding of E-cadherin-mediated events in native micro-environments. This abstract is also being presented as Poster B23. Citation Format: David Herrmann, Zahra Erami, Sean Warren, Max Nobis, Astrid Magenau, Morghan Lucas, Claire Vennin, Ewan J. McGhee, Wilfred Leung, Nadine Reischmann, Agata Mrowinska, Juliane P. Schwarz, Shereen Kadir, Saadia A. Karim, Andrew D. Campbell, David Gallego-Ortega, Jeffry Evans, Owen J. Sansom, Jennifer P. Morton, Kurt I. Anderson, Paul Timpson. A biosensor mouse to predict the dissociation and spread of pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston,...

Ho-Le, TP, Center, JR, Eisman, JA, Nguyen, TV & Nguyen, HT 1970, 'Prediction of hip fracture in post-menopausal women using artificial neural network approach', 2017 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2017 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), IEEE, Jeju Island, Korea, pp. 4207-4210.
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Hip fracture is one of the most serious health problems among post-menopausal women with osteoporosis. It is very difficult to predict hip fracture, because it is affected by multiple risk factors. Existing statistical models for predicting hip fracture risk yield area under the receiver operating characteristic curve (AUC) ~0.7-0.85. In this study, we trained an artificial neural network (ANN) to predict hip fracture in one cohort, and validated its predictive performance in another cohort. The data for training and validation included age, bone mineral density (BMD), clinical factors, and lifestyle factors which had been obtained from a longitudinal study that involved 1167 women aged 60 years and above. The women had been followed up for up to 10 years, and during the period, the incidence of new hip fractures was ascertained. We applied feed-forward neural networks to learn from the data, and then used the learning for predicting hip fracture. Results of prediction showed that the accuracy of model I (which included only lumbar spine and femoral neck BMD) and model II (which included non-BMD factors) was 82% and 84%, respectively. When both BMD and non-BMD factors were combined (Model III), the accuracy increased to 87%. The AUC for model III was 0.94. These findings indicate that ANNs are able to predict hip fracture more accurately than any existing statistical models, and that ANNs can help stratify individuals for clinical management.

Pham, NH, Nguyen, TB, Le, HP, Pham, DT, Ho-Pham, LT, Duong, TD & Nguyen, TV 1970, 'Bisphosphonates for Osteoporosis Treatment: A Cost-Effectiveness Analysis in Vietnamese Woman', Value in Health, Elsevier BV, pp. A535-A535.
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Razavi Bazaz, S, Hazeri, A & Abouei Mchrizi, A 1970, 'Increasing Efficiency of Micromixing Within a Biomicrofluidic Device Using Acceleration, Deceleration Technique', 2017 24th National and 2nd International Iranian Conference on Biomedical Engineering (ICBME), 2017 24th National and 2nd International Iranian Conference on Biomedical Engineering (ICBME), IEEE.
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The main aim of this study is applying the concept of a mechanical phenomenon into a biomicrofluidic device, which is a micromixer, to increase its efficiency in terms of mixing index for biological applications. The main feature of this enhancement is that the total volume of fluid does not change during this process. The geometry of a square-wave micromixer as an accepted and custom micromixer of biomicrofluidic devices is manipulated by using a nozzle-diffuser channel shape instead of a straight one. By using this approach, the fluids are accelerated and decelerated simultaneously and result in additional chaotic advection to decrease diffusion path and increase mixing efficiency. The computational fluid dynamics (CFD) is used for simulation of this process in a three-dimensional framework. COMSOL Multiphysics, a commercial CFD package based on finite element method, is used to perform numerical simulations. The proposed device is simulated in Re number of 0.001 to 60 in order to better understanding the function of the device in a wide range of Re number. The results are then analyzed and illustrated that in Re number of 1, which is a critical Re number in most devices, the mixing index increased from 38.7 to 61.7 which is completely satisfactory and in Re number of 5, mixing index enhanced from 41.6 to 63.8. All in all, the proposed micromixer demonstrated a significant performance in a wide range of Re number and can be suitable as a preliminary stage and an important component in biomicrofluidic devices, especially the ones that mixing two reagents is a preliminary stage.

Schwarzer, A, Emmrich, S, Beck, D, Schmidt, F, Ng, M, Adams, FF, Witte, D, Kaebler, S, Wong, JWH, Shah, A, Jammal, R, Maroz, A, Reimer, C, Pimanda, JE, Reinhardt, D, Heckl, D & Klusmann, J-H 1970, 'Mapping the Lncrna-Landscape of Human Hematopoiesis and Leukemia Reveals Stem Cell Non-Coding Gene Expression Programs', ANNALS OF HEMATOLOGY, SPRINGER, pp. S51-S51.