Publications

Di, X, Qin, J, Sun, Y & Su, QP 2023, 'Visualize the Distribution and Dynamics of Mitochondrial DNA (mtDNA) Nucleoids with Multiple Labeling Strategies' in Methods in Molecular Biology, Springer US, pp. 79-88.
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Matthews, N, Ly, S, West, D & Gentile, C 2023, '3D Bioprinting for Cardiovascular Applications' in Muñoz, JLP, Martínez, LSDB, Ochoa, GP & Sesma, JZ (eds), 3D Printing and Bioprinting for Pharmaceutical and Medical Applications, CRC Press, Boca Raton, pp. 169-190.
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Cardiovascular disease remains one of the major causes of death globally, and a heart transplant is the gold standard treatment for end-stage heart failure patients. However, a successful transplantation is dependent on organ donor’s limited availability and poses several clinical and economical risk factors for the patient, their families and more broadly the whole health system. 3D bioprinting technologies combined with tissue engineering and regenerative medicine have shown promising results in better recapitulating the natural microenvironment of the human body and in providing a future alternative for organ transplants. In this approach, the precise deposition of cellular material in permissive biomaterials suitable for tissue-specific cells has demonstrated advancements for cardiac tissue transplantation. In particular, the use of patient-derived stem cells for 3D bioprinting provides a personalised treatment specific for each patient, which also prevents the risk of rejection and may lead to faster recovery following the surgical procedure. This book chapter presents the current state of 3D bioprinting technologies applied for personalised cardiac patches. First, an overview of human cardiac anatomy and the impact of myocardial infarction are then followed by a comparison of 3D bioprinting methods, commonly used biomaterials, and the characteristics of cells and cellular spheroids. This is followed by a closer look at animal studies using 3D bioprinted cardiac patches to date and highlights major challenges for the translation of this approach to the clinic. Finally, considerations around biological and design requirements to develop personalised cardiac patches are introduced for future potential directions in cardiovascular 3D bioprinting.

Rad, HS, Shiravand, Y, Radfar, P, Ladwa, R, Warkiani, ME, O’Byrne, K & Kulasinghe, A 2023, 'Spatial Transcriptomic Approaches for Understanding the Tumor Microenvironment (TME)' in Interdisciplinary Cancer Research, Springer Nature Switzerland, pp. 49-77.
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Radfar, P, Es, HA, Kulasinghe, A, Thiery, JP & Warkiani, ME 2023, 'Circulating Tumour Cell Isolation and Molecular Profiling; Potential Therapeutic Intervention' in Circulating Tumor Cells, Springer International Publishing, pp. 359-385.
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Comprehensive tumour characterisation is indispensable for patients to receive targeted therapy. The use of liquid biopsy, particularly circulating tumour cells (CTC), has shown great promise in the treatment and management of cancer patients. An in-depth understanding of CTCs at the cellular and molecular level can provide clues as to the mechanisms of cancer dissemination and the pathways responsible for conferring intrinsic and acquired resistance to therapeutic agents. Herein, we discuss the current methods of CTC isolation and analysis at the single-cell resolution for therapeutic applications in the management of cancer.

Ahmadi, S, Ebrahimi Warkiani, M, Rabiee, M, Iravani, S & Rabiee, N 2023, 'Carbon-based nanomaterials against SARS-CoV-2: Therapeutic and diagnostic applications', OpenNano, vol. 10, pp. 100121-100121.
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Alajlouni, DA, Bliuc, D, Tran, TS, Blank, RD & Center, JR 2023, 'Muscle strength and physical performance contribute to and improve fracture risk prediction in older people: A narrative review', Bone, vol. 172, pp. 116755-116755.
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Alarkawi, D, Tran, T, Chen, W, March, LM, Blyth, FM, Blank, RD, Bliuc, D & Center, JR 2023, 'Denosumab and Mortality in a Real-World Setting: A Comparative Study', Journal of Bone and Mineral Research, vol. 38, no. 12, pp. 1757-1770.
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ABSTRACT Denosumab (Dmab) is increasingly prescribed worldwide. Unlike bisphosphonates (BPs), its effect on mortality has yet to be well explored. This study examined the association between Dmab and all-cause mortality compared with no treatment in subjects with a fracture and BPs in subjects without a fracture. The study population was from the Sax Institute's 45 and Up Study (n = 267,357), a prospective population-based cohort with questionnaire data linked to hospital admissions (Admitted Patients Data Collection [APDC] data were linked by the Centre for Health Record Linkage), medication records (Pharmaceutical Benefits Scheme [PBS] provided by Services Australia), and stored securely (secure data access was provided through the Sax Institute's Secure Unified Research Environment [SURE]). The new-user cohort design with propensity-score (PS) matching was implemented. In the fracture cohort, Dmab and oral BP users were matched 1:2 to no treatment (Dmab: 617 women, 154 men; oral BPs: 615 women, 266 men). In the no-fracture cohort, Dmab users were matched 1:1 with oral BPs and zoledronic acid (Zol) users (Dmab:oral BPs: 479 men, 1534 women; Dmab:Zol: 280 men, 625 women). Mortality risk was measured using sex-specific pairwise multivariable Cox models. In the fracture cohort, compared with no treatment, Dmab was associated with 48% lower mortality in women (hazard ratio [HR] = 0.52, 95% confidence interval [CI] 0.36–0.72) but not in men. Oral BPs were associated with 44% lower mortality in both sexes (women HR = 0.56, 95% CI 0.42–0.77; men HR = 0.56, 95% CI 0.40–0.78). In the no-fracture cohort, compared with BPs, Dmab was associated with 1.5- to 2.5-fold higher mortality than oral BPs (women HR = 1.49, 95% CI 1.13–1.98; men HR = 2.74; 95% CI 1.82–4.11) but similar mortality to Zol. Dmab in women and oral BPs were associated with lower post-fracture mortality than no treatment. However, Dmab users had gen...

Bahrami, H, Sichetti, F, Puppo, E, Vettori, L, Liu Chung Ming, C, Perry, S, Gentile, C & Pietroni, N 2023, 'Physically-based simulation of elastic-plastic fusion of 3D bioprinted spheroids', Biofabrication, vol. 15, no. 4, pp. 045021-045021.
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Abstract Spheroids are microtissues containing cells organized in a spherical shape whose diameter is usually less than a millimetre. Depending on the properties of the environment they are placed in, some nearby spheroids spontaneously fuse and generate a tissue. Given their potential to mimic features typical of body parts and their ability to assemble by fusing in permissive hydrogels, they have been used as building blocks to 3D bioprint human tissue parts. Parameters controlling the shape and size of a bioprinted tissue using fusing spheroid cultures include cell composition, hydrogel properties, and their relative initial position. Hence, simulating, anticipating, and then controlling the spheroid fusion process is essential to control the shape and size of the bioprinted tissue. This study presents the first physically-based framework to simulate the fusion process of bioprinted spheroids. The simulation is based on elastic-plastic solid and fluid continuum mechanics models. Both models use the ‘smoothed particle hydrodynamics’ method, which is based on discretizing the continuous medium into a finite number of particles and solving the differential equations related to the physical properties (e.g. Navier–Stokes equation) using a smoothing kernel function. To further investigate the effects of such parameters on spheroid shape and geometry, we performed sensitivity and morphological analysis to validate our simulations with in-vitro spheroids. Through our in-silico simulations by changing the aforementioned parameters, we show that the proposed models appropriately simulate the range of the elastic-plastic behaviours of in-vitro fusing spheroids to generate tissues of desired shapes and sizes. Altogether, this study presented a physically-based simulation that can provide a framework for monitoring and controlling the ...

Bliuc, D, Tran, T, Chen, W, Alarkawi, D, Alajlouni, DA, Blyth, F, March, L, Blank, RD & Center, JR 2023, 'Antiresorptive Medication Use Is not Associated With Acute Cardiovascular Risk: An Observational Study', The Journal of Clinical Endocrinology & Metabolism, vol. 108, no. 5, pp. e110-e119.
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AbstractContextBisphosphonates have been reported to be cardioprotective in some, but not all, studies. It is unknown whether denosumab (Dmab) use protects against cardiovascular events (CVEs).ObjectiveTo determine whether oral bisphosphonate (oBP) or Dmab use is associated with CVEs in persons with incident fracture.MethodsParticipants with an incident minimal trauma fracture from the Sax Institute’s 45 and Up Study, a population-based cohort from NSW, Australia, were followed between 2005/2009 and 2017. Questionnaire data were linked to hospital admissions (Admitted Patients Data Collection [APDC]) by the Centre for Health Record Linkage). Medicare Benefit Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) data sets were provided by Services Australia. Data was stored in a secure computing environment (Secure Unified Research Environment). Fractures, CVEs, and comorbidities were identified from the APDC and oBP and Dmab medication from the PBS. oBP and Dmab users were matched to never users (NoRx) by propensity scores. The main outcome measures were association between oBP and Dmab with CVE (acute myocardial infarction, unstable angina, cerebrovascular accident, and transient ischemic attack) and were determined using a stratified Cox's proportional hazards model.ResultsThere were 880 pairs of oBP and NoRx (616 women) and 770 pairs of Dmab and NoRx (615 women) followed for ∼4.3 years. CVE risk was similar for oBP and NoRx Hazard Ratios (HR) women, 0.88 [95% CI 0.65-1.18]; men, 1.07 [95% CI 0.72-1.57]). Similar findings were obtained for Dmab (Hazard Ratios (HR) women, 1.08 [95% CI 0.78-1.50]; men, 1.55 [95% CI 0.96-2.48]).Conclusion...

Ceballos‐González, CF, Bolívar‐Monsalve, EJ, Quevedo‐Moreno, DA, Chávez‐Madero, C, Velásquez‐Marín, S, Lam‐Aguilar, LL, Solís‐Pérez, ÓE, Cantoral‐Sánchez, A, Neher, M, Yzar‐García, E, Zhang, YS, Gentile, C, Boccaccini, AR, Alvarez, MM & Trujillo‐de Santiago, G 2023, 'Plug‐and‐Play Multimaterial Chaotic Printing/Bioprinting to Produce Radial and Axial Micropatterns in Hydrogel Filaments', Advanced Materials Technologies, vol. 8, no. 17.
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AbstractNature abounds with micro‐architected materials containing layered multi‐material patterns that often transition within the very same monolithic piece. Fabricating these complex materials using current technologies is challenging. Multimaterial chaotic printing is presented—an extrusive printing method based on the use of chaotic advection—that can fabricate microstructured hydrogels with well‐defined multimaterial and multilayered micropatterns. Printheads containing internal Kenics static mixing (KSM) elements and top‐ and lateral‐positioned inlets are used to produce a wide repertoire of multilayered hydrogel filaments. In this plug‐and‐play system, the radial and axial micropatterns can be designed ad hoc by defining the printhead configuration (i.e., the number of KSM elements and inlets, and the inlet positions) and the flow program (i.e., activation/deactivation of the ink‐flow through each inlet). Computational fluid dynamics simulations closely predict the microstructure obtained by a given printhead configuration. The application of this platform is illustrated for easy fabrication of fibers with radial microgradients, bacterial ecosystems, structured emulsions, micro‐channeled hydrogel filaments, a pre‐vascularized tumor niche model, and skeletal muscle‐like tissues with axial and radial transitions of bioactive glass compartments. It is envisioned that multimaterial chaotic printing will be a valuable addition to the toolbox of additive manufacturing for the rational fabrication of advanced materials.

Ceballos‐González, CF, Bolívar‐Monsalve, EJ, Quevedo‐Moreno, DA, Chávez‐Madero, C, Velásquez‐Marín, S, Lam‐Aguilar, LL, Solís‐Pérez, ÓE, Cantoral‐Sánchez, A, Neher, M, Yzar‐García, E, Zhang, YS, Gentile, C, Boccaccini, AR, Alvarez, MM & Trujillo‐de Santiago, G 2023, 'Plug‐and‐Play Multimaterial Chaotic Printing/Bioprinting to Produce Radial and Axial Micropatterns in Hydrogel Filaments (Adv. Mater. Technol. 17/2023)', Advanced Materials Technologies, vol. 8, no. 17.
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Challis, VJ, Xu, X, Halfpenny, A, Cramer, AD, Saunders, M, Roberts, AP & Sercombe, TB 2023, 'Understanding the effect of microstructural texture on the anisotropic elastic properties of selective laser melted Ti-24Nb-4Zr-8Sn', Acta Materialia, vol. 254, pp. 119021-119021.
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Chen, R, Pye, JS, Li, J, Little, CB & Li, JJ 2023, 'Multiphasic scaffolds for the repair of osteochondral defects: Outcomes of preclinical studies', Bioactive Materials, vol. 27, pp. 505-545.
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Choi, WWY, Sánchez, C, Li, JJ, Dinarvand, M, Adomat, H, Ghaffari, M, Khoja, L, Vafaee, F, Joshua, AM, Chi, KN, Guns, EST & Hosseini-Beheshti, E 2023, 'Extracellular vesicles from biological fluids as potential markers in castration resistant prostate cancer', Journal of Cancer Research and Clinical Oncology, vol. 149, no. 8, pp. 4701-4717.
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Abstract Purpose Extracellular vesicles (EV) secreted from cancer cells are present in various biological fluids, carrying distinctly different cellular components compared to normal cells, and have great potential to be used as markers for disease initiation, progression, and response to treatment. This under-utilised tool provides insights into a better understanding of prostate cancer. Methods EV from serum and urine of healthy men and castration-resistant prostate cancer (CRPC) patients were isolated and characterised by transmission electron microscopy, particle size analysis, and western blot. Proteomic and cholesterol liquid chromatography-mass spectrometry (LC–MS) analyses were conducted. Results There was a successful enrichment of small EV/exosomes isolated from serum and urine. EV derived from biological fluids of CRPC patients had significant differences in composition when compared with those from healthy controls. Analysis of matched serum and urine samples from six prostate cancer patients revealed specific EV proteins common in both types of biological fluid for each patient. Conclusion Some of the EV proteins identified from our analyses have potential to be used as CRPC markers. These markers may depict a pattern in cancer progression through non-invasive sample collection.

Ci, Q, Wang, Y, Wu, B, Coy, E, Li, JJ, Jiang, D, Zhang, P & Wang, G 2023, 'Fe‐Doped Carbon Dots as NIR‐II Fluorescence Probe for In Vivo Gastric Imaging and pH Detection', Advanced Science, vol. 10, no. 7, pp. e2206271-2206271.
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AbstractCarbon dots (CDs) with excellent cytocompatibility, tunable optical properties, and simple synthesis routes are highly desirable for use in optical bioimaging. However, the majority of existing CDs are triggered by ultraviolet/blue light, presenting emissions in the visible/first near‐infrared (NIR‐I) regions, which do not allow deep tissue penetration. Emerging research into CDs with NIR‐II emission in the red region has generated limited designs with poor quantum yield, restricting their in vivo imaging applications due to low penetration depth. Developing novel CDs with NIR‐II emissions and high quantum yield has significant and far‐reaching applications in bioimaging and photodynamic therapy. Here, it is developed for the first time Fe‐doped CDs (Fe‐CDs) exhibiting the excellent linear relationship between 900–1200 nm fluorescence‐emission and pH values, and high quantum yield (QY‐1.27%), which can be used as effective probes for in vivo NIR‐II bioimaging. These findings demonstrate reliable imaging accuracy in tissue as deep as 4 mm, reflecting real‐time pH changes comparable to a standard pH electrode. As an important example application, the Fe‐CDs probe can non‐invasively monitor in vivo gastric pH changes during the digestion process in mice, illustrating its potential applications in aiding imaging‐guided diagnosis of gastric diseases or therapeutic delivery.

Crowther, CA, Ashwood, P, Middleton, PF, McPhee, A, Tran, T, Harding, JE, Alsweiler, J, Baker, E, Eaglen, D, Groom, K, Hauch, H, Mackay, L, Pacella, MJ, Preest, A, Taylor, J, Williamson, K, Tottman, A, Austin, N, Darlow, BA, Dixon, B, Ellis, N, Graham, P, Gullam, J, Leishman, D, Van Dyk, MM, Broadbent, R, Dawson, P, Devenish, C, Douglas, J, McCaffrey, F, Carey, R, Marshall, P, Morris, S, Nguyen, T, Gaerty, K, Grupp, O, Boddice, G, Green, A, Mahomed, K, Turner, L, Baldwin, M, Dennis, A, Fisher, E, Gee, K, Gee, M, Strong, D, Asadi, S, Burakevych, N, Griffth, R, Kendaragama, A, Ksionda, O, Kurkchi, K, Paine, C, Philipsen, S, Rogers, J, Samuel, D, Shah, R, Slabkevich, N, Stewart, H, Vasilenko, A, Beckman, M, Bolton, E, Chaplin, J, Cooper, C, Fox, J, Gray, P, Hawley, G, Hickey, J, Hoey, J, Hurrion, E, Jardine, L, Kan, J, Lynn, L, McHale, T, Poad, D, Poulsen, L, Warhurst, K, Bice, C, Davis, N, Duff, J, Jones, A, Kelly, EA, Magrath, E, Malcolm, D, O'Connor, K-A, Opie, G, Turner, A-M, Walker, S, Williamson, A, Woods, H, Hou, D, Kippen, M, Schroder, J, Thesing, AJ, Wadsworth, S, Camadoo, L, Dyer, C, Jones, S, Kothari, A, Markovic, V, Owens, J, Shallcross, M, Butterley, K, Davis, C, De Paoli, A, Dodson, S, Holmes, M, Kenchapla, H, Matzolic, T, McGregor, A, Patel, S, Simic, S, Andrijic, V, Biggs, V, Brandrick, S, Goldstein, S, Lainchbury, A, Lui, K, Lyons, S, Shand, A, Sutton, L, Barnes, L, Bowen, J, Harvey, L, Jacobs, C, Milligan, J, Morris, J, Nippita, T, Sau-Harvey, R, Sparks, A, Wegener, A, Burnett, A, Callanan, K, Cheong, J, De Luca, C, Doyle, L, du Plessis, J, Duff, J, Hutchinson, E, Kane, SC, Kelly, E, Kornman, L, Maxwell, D, McDonald, M, Poth, M, Arcus, JC, Cruickshank, M, Devoy, B, Fanning, MJ, Henriksen, K, Morse, F, Schiller, A, Tomlinson, PA, Davis, G, Dosen, A, Roberts, L, Rowe, C, Creen, J, Gee, K, Hurley, T, Pallett, L, Smitheram, C, Thompson, A, Weaver, E, Lynch, L-A, Pszczola, R, Said, J, Shekleton, J, Craine, K, Fergus, J, Ford, J, Harris, A, Kummer, M, Thurnell, C, Boniface, C, Davis, A, Dickinson, C, Ireland, S, Lawrence, A, Mandell, K, Menon, S, Watson, D, Bennett, M, Elder, R, Hayne, P, Massov, L, Miller, H, Sandler, ME, Schenk, V, Wilkes, N, Sibanda, T, Davis, W, Dill, N, Espinoza, N, Kunjunju, A, Wright, I, Anderson, C, Ball, V, Bhatia, V, Burford-Rice, R, Gagliardi, D, Gooding, ML, Han, S, Headley, B, Holst, C, Keir, A, Khong, TY, Kochar, A & et al. 2023, 'Prenatal Intravenous Magnesium at 30-34 Weeks’ Gestation and Neurodevelopmental Outcomes in Offspring', JAMA, vol. 330, no. 7, pp. 603-603.
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ImportanceIntravenous magnesium sulfate administered to pregnant individuals before birth at less than 30 weeks’ gestation reduces the risk of death and cerebral palsy in their children. The effects at later gestational ages are unclear.ObjectiveTo determine whether administration of magnesium sulfate at 30 to 34 weeks’ gestation reduces death or cerebral palsy at 2 years.Design, Setting, and ParticipantsThis randomized clinical trial enrolled pregnant individuals expected to deliver at 30 to 34 weeks’ gestation and was conducted at 24 Australian and New Zealand hospitals between January 2012 and April 2018.InterventionIntravenous magnesium sulfate (4 g) was compared with placebo.Main Outcomes and MeasuresThe primary outcome was death (stillbirth, death of a live-born infant before hospital discharge, or death after hospital discharge before 2 years’ corrected age) or cerebral palsy (loss of motor function and abnormalities of muscle tone and power assessed by a pediatrician) at 2 years’ corrected age. There were 36 secondary outcomes that assessed the health of the pregnant individual, infant, and child.ResultsOf the 1433 pregnant individuals enrolled (mean age, 30.6 [SD, 6.6] years; 46 [3.2%] self-identified as Aboriginal or Torres Strait Islander, 237 [16.5%] as Asian, 82 [5.7%] as Māori, 61 [4.3%] as Pacific, and 966 [67.4%] as White) and their 1679 infants, 1365 (81%) offspring (691 in the magnesium group and 674 in the placebo group) were included in the primary outcome analysis. Death or cerebral palsy at 2 years’ corrected age was not significantly different between the magnesium and placebo gr...

Crowther, CA, Samuel, D, McCowan, LME, Edlin, R, Tran, T & McKinlay, CJ 2023, 'Lower Versus Higher Glycemic Criteria for Diagnosis of Gestational Diabetes', Obstetrical & Gynecological Survey, vol. 78, no. 2, pp. 85-87.
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ABSTRACT Gestational diabetes mellitus (GDM) in pregnancy is a global health problem. Maternal risks associated with this condition include higher rates of induced labor, cesarean delivery, and preeclampsia. Fetal exposure to GDM can increase the risk of large for gestational age (LGA), as well as operative birth, shoulder dystocia, and birth injuries. To reduce these risks, GDM is managed with nutritional therapy, blood glucose monitoring, and pharmacologic treatment. However, the criteria to diagnose GDM in pregnant individuals vary globally. Although the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommends using a lower glycemic threshold to diagnose maternal hyperglycemia, its adoption has been mixed. The aim of this study was to evaluate whether lower glycemic criteria to diagnosis GDM would improve perinatal and maternal outcomes. This was a randomized trial conducted in 2 health boards in New Zealand between April 2015 and August 2020. Included were women with singleton pregnancies who had a 75-g oral glucose tolerance test (OGTT) at 24 to 32 weeks of gestation. Excluded were those with diabetes mellitus or a history of GDM. The women were randomly assigned to be evaluated for GDM using lower glycemic criteria for diagnosis or higher criteria in a 1:1 ratio. The lower criteria were defined as a fasting plasma glucose level ≥5.1 mmol/L, a 1-hour level ≥10.1 mmol/L, or a 2-hour level ≥8.5 mmol/L. The higher criterion was a fasting plasma glucose level ≥5.5 mmol/L or a 2-hour level ≥9 mmol/L. The primary outcome was LGA. A total of 4050 women and their infants were randomized and included in the analysis—2019 in the lower criteria group and 2013 in the higher criteria group. There were 8.8% LGA infants born in the lower criteria group and 8.9% in the higher criteria group (unadjusted relative risk, 0.99; 95% confidence int...

Cui, Y, Miao, MZ, Wang, M, Su, QP, Qiu, K, Arbeeva, L, Chubinskaya, S, Diekman, BO & Loeser, RF 2023, 'Yes-associated protein nuclear translocation promotes anabolic activity in human articular chondrocytes', Osteoarthritis and Cartilage, vol. 31, no. 8, pp. 1078-1090.
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OBJECTIVE: Yes-associated protein (YAP) has been widely studied as a mechanotransducer in many cell types, but its function in cartilage is controversial. The aim of this study was to identify the effect of YAP phosphorylation and nuclear translocation on the chondrocyte response to stimuli relevant to osteoarthritis (OA). DESIGN: Cultured normal human articular chondrocytes from 81 donors were treated with increased osmolarity media as an in vitro model of mechanical stimulation, fibronectin fragments (FN-f) or IL-1β as catabolic stimuli, and IGF-1 as an anabolic stimulus. YAP function was assessed with gene knockdown and inhibition by verteporfin. Nuclear translocation of YAP and its transcriptional co-activator TAZ and site-specific YAP phosphorylation were determined by immunoblotting. Immunohistochemistry and immunofluorescence to detect YAP were performed on normal and OA human cartilage with different degrees of damage. RESULTS: Chondrocyte YAP/TAZ nuclear translocation increased under physiological osmolarity (400 mOsm) and IGF-1 stimulation, which was associated with YAP phosphorylation at Ser128. In contrast, catabolic stimulation decreased the levels of nuclear YAP/TAZ through YAP phosphorylation at Ser127. Following YAP inhibition, anabolic gene expression and transcriptional activity decreased. Additionally, YAP knockdown reduced proteoglycan staining and levels of type II collagen. Total YAP immunostaining was greater in OA cartilage, but YAP was sequestered in the cytosol in cartilage areas with more severe damage. CONCLUSIONS: YAP chondrocyte nuclear translocation is regulated by differential phosphorylation in response to anabolic and catabolic stimuli. Decreased nuclear YAP in OA chondrocytes may contribute to reduced anabolic activity and promotion of further cartilage loss.

Ding, L, Oh, S, Shrestha, J, Lam, A, Wang, Y, Radfar, P & Warkiani, ME 2023, 'Scaling up stem cell production: harnessing the potential of microfluidic devices', Biotechnology Advances, vol. 69, pp. 108271-108271.
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Dong, S, Mei, F, Li, JJ & Xing, D 2023, 'Global Cluster Analysis and Network Visualization in Prosthetic Joint Infection: A Scientometric Mapping', Orthopaedic Surgery, vol. 15, no. 4, pp. 1165-1178.
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ObjectiveProsthetic joint infection (PJI) is the main reason of failure of total joint arthroplasty (TJA). This study aimed to investigate the global trends and network visualization in research of PJI.MethodsPublications in PJI search during 1980–2022 were extracted from the Science Citation Index‐Expanded of Web of Science Core Collection database (WoSCC). The source data was investigated and analyzed by bibliometric methodology. For network visualization, VOS viewer and R software was used to perform bibliographic coupling, co‐citation, co‐authorship and co‐occurrence analysis and to predict the publication trends in PJI research.ResultsThere were 7288 articles included. The number of publications and relative research interests increased gradually per year globally. The USA made the highest contributions in the world and with the highest H‐index and the most citations. Journal of Arthroplasty published the highest number of articles in this area. The Mayo Clinic, Thomas Jefferson University (Rothman Institute), Hospital Special Surgery and the Rush University were the most contributive institutions by network visualization. Included studies were divided into four clusters: bacterial pathogenic mechanism and antibacterial drugs study, TJA complications, risk factors and epidemiology of PJI, diagnosis of PJI, and revision surgical management. More articles in PJI could be published over the next few years.ConclusionThe number of publications about PJI will be increasing dramatically based on the global trends and network visualization. The USA made the highest contributions in PJI. Diagnosis and revision management may be the next hot spots in this field.

Du, S, Shen, Y, Zheng, Y, Cheng, Y, Xu, X, Chen, D & Xia, D 2023, 'Systematic in vitro and in vivo study on biodegradable binary Zn-0.2 at% Rare Earth alloys (Zn-RE: Sc, Y, La–Nd, Sm–Lu)', Bioactive Materials, vol. 24, pp. 507-523.
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Entezari, A, Liu, N-C, Zhang, Z, Fang, J, Wu, C, Wan, B, Swain, M & Li, Q 2023, 'Nondeterministic multiobjective optimization of 3D printed ceramic tissue scaffolds', Journal of the Mechanical Behavior of Biomedical Materials, vol. 138, pp. 105580-105580.
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Farhart, P, Beakley, D, Diwan, A, Duffield, R, Rodriguez, EP, Chamoli, U & Watsford, M 2023, 'Intrinsic variables associated with low back pain and lumbar spine injury in fast bowlers in cricket: a systematic review', BMC Sports Science, Medicine and Rehabilitation, vol. 15, no. 1, p. 114.
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Abstract Background Lumbar spine injuries in fast bowlers account for the greatest missed playing time in cricket. A range of extrinsic and intrinsic variables are hypothesised to be associated with low back pain and lumbar spine injury in fast bowlers, and an improved understanding of intrinsic variables is necessary as these may alter load tolerance and injury risk associated with fast bowling. This review critically evaluated studies reporting intrinsic variables associated with low back pain and lumbar spine injury in fast bowlers and identified areas for future investigation. Methods OVID Medline, EMBASE, SPORTDiscus, CINAHL, Web of Science and SCOPUS databases were last searched on 3 June 2022 to identify studies investigating intrinsic variables associated with low back pain and lumbar spine injury in cricket fast bowlers. Terms relevant to cricket fast bowling, and intrinsic variables associated with lumbar spine injury and low back pain in fast bowlers were searched. 1,503 abstracts were screened, and 118 full‐text articles were appraised to determine whether they met inclusion criteria. Two authors independently screened search results and assessed risk of bias using a modified version of the Quality in Prognostic Studies tool. Results Twenty-five studies met the inclusion criteria. Overall, no included studies demonstrated a low risk of bias, two studies were identified as moderate risk, and twenty-three studies were identified as high risk. Conflicting results were reported amongst studies investigating associations of fast bowling kinematics and kinetics, trunk and lumbar anatomical features, anthropometric traits, age, and ne...

Gadde, S, Kleynhans, A, Holien, JK, Bhadbhade, M, Nguyen, PLD, Mittra, R, Yu, TT, Carter, DR, Parker, MW, Marshall, GM, Cheung, BB & Kumar, N 2023, 'Pyrimido[1,2-a]benzimidazoles as inhibitors of oncoproteins ubiquitin specific protease 5 and MYCN in the childhood cancer neuroblastoma', Bioorganic Chemistry, vol. 136, pp. 106462-106462.
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Ganguly, D, Schmidt, MO, Coleman, M, Ngo, T-VC, Sorrelle, N, Dominguez, ATA, Murimwa, GZ, Toombs, JE, Lewis, C, Fang, YV, Valdes-Mora, F, Gallego-Ortega, D, Wellstein, A & Brekken, RA 2023, 'Pleiotrophin drives a prometastatic immune niche in breast cancer', Journal of Experimental Medicine, vol. 220, no. 5.
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Metastatic cancer cells adapt to thrive in secondary organs. To investigate metastatic adaptation, we performed transcriptomic analysis of metastatic and non-metastatic murine breast cancer cells. We found that pleiotrophin (PTN), a neurotrophic cytokine, is a metastasis-associated factor that is expressed highly by aggressive breast cancers. Moreover, elevated PTN in plasma correlated significantly with metastasis and reduced survival of breast cancer patients. Mechanistically, we find that PTN activates NF-κB in cancer cells leading to altered cytokine production, subsequent neutrophil recruitment, and an immune suppressive microenvironment. Consequently, inhibition of PTN, pharmacologically or genetically, reduces the accumulation of tumor-associated neutrophils and reverts local immune suppression, resulting in increased T cell activation and attenuated metastasis. Furthermore, inhibition of PTN significantly enhanced the efficacy of immune checkpoint blockade and chemotherapy in reducing metastatic burden in mice. These findings establish PTN as a previously unrecognized driver of a prometastatic immune niche and thus represents a promising therapeutic target for the treatment of metastatic breast cancer.

Ghorbanpour, SM, Richards, C, Pienaar, D, Sesperez, K, Aboulkheyr Es., H, Nikolic, VN, Karadzov Orlic, N, Mikovic, Z, Stefanovic, M, Cakic, Z, Alqudah, A, Cole, L, Gorrie, C, McGrath, K, Kavurma, MM, Ebrahimi Warkiani, M & McClements, L 2023, 'A placenta-on-a-chip model to determine the regulation of FKBPL and galectin-3 in preeclampsia', Cellular and Molecular Life Sciences, vol. 80, no. 2.
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AbstractPreeclampsia is a pregnancy-specific cardiovascular disorder, involving significant maternal endothelial dysfunction. Although inappropriate placentation due to aberrant angiogenesis, inflammation and shallow trophoblast invasion are the root causes of preeclampsia, pathogenic mechanisms are poorly understood, particularly in early pregnancy. Here, we first confirm the abnormal expression of important vascular and inflammatory proteins, FK506-binding protein-like (FKBPL) and galectin-3 (Gal-3), in human plasma and placental tissues from women with preeclampsia and normotensive controls. We then employ a three-dimensional microfluidic placental model incorporating human umbilical vein endothelial cells (HUVECs) and a first trimester trophoblast cell line (ACH-3P) to investigate FKBPL and Gal-3 signaling in inflammatory conditions. In human samples, both circulating (n = 17 controls; n = 30 preeclampsia) and placental (n ≥ 6) FKBPL and Gal-3 levels were increased in preeclampsia compared to controls (plasma: FKBPL, p < 0.0001; Gal-3, p < 0.01; placenta: FKBPL, p < 0.05; Gal-3, p < 0.01), indicative of vascular dysfunction in preeclampsia. In our placenta-on-a-chip model, we show that endothelial cells are critical for trophoblast-mediated migration and that trophoblasts effectively remodel endothelial vascular networks. Inflammatory cytokine tumour necrosis factor-α (10 ng/mL) modulates both FKBPL and Gal-3 signaling in conjunction with trophoblast migration and impairs vascular network formation (p < 0.005). Our placenta-on-a-chip recapitulates aspects of inappropriate placental development and vascular dysfunction in preeclampsia.

Goss, DM, Vasilescu, SA, Sacks, G, Gardner, DK & Warkiani, ME 2023, 'Microfluidics facilitating the use of small extracellular vesicles in innovative approaches to male infertility', Nature Reviews Urology, vol. 20, no. 2, pp. 66-95.
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Sperm are transcriptionally and translationally quiescent and, therefore, rely on the seminal plasma microenvironment for function, survival and fertilization of the oocyte in the oviduct. The male reproductive system influences sperm function via the binding and fusion of secreted epididymal (epididymosomes) and prostatic (prostasomes) small extracellular vesicles (S-EVs) that facilitate the transfer of proteins, lipids and nucleic acids to sperm. Seminal plasma S-EVs have important roles in sperm maturation, immune and oxidative stress protection, capacitation, fertilization and endometrial implantation and receptivity. Supplementing asthenozoospermic samples with normospermic-derived S-EVs can improve sperm motility and S-EV microRNAs can be used to predict non-obstructive azoospermia. Thus, S-EV influence on sperm physiology might have both therapeutic and diagnostic potential; however, the isolation of pure populations of S-EVs from bodily fluids with current conventional methods presents a substantial hurdle. Many conventional techniques lack accuracy, effectiveness, and practicality; yet microfluidic technology has the potential to simplify and improve S-EV isolation and detection.

Haghighitalab, A, Dominici, M, Matin, MM, Shekari, F, Ebrahimi Warkiani, M, Lim, R, Ahmadiankia, N, Mirahmadi, M, Bahrami, AR & Bidkhori, HR 2023, 'Extracellular vesicles and their cells of origin: Open issues in autoimmune diseases', Frontiers in Immunology, vol. 14, p. 1090416.
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The conventional therapeutic approaches to treat autoimmune diseases through suppressing the immune system, such as steroidal and non-steroidal anti-inflammatory drugs, are not adequately practical. Moreover, these regimens are associated with considerable complications. Designing tolerogenic therapeutic strategies based on stem cells, immune cells, and their extracellular vesicles (EVs) seems to open a promising path to managing autoimmune diseases’ vast burden. Mesenchymal stem/stromal cells (MSCs), dendritic cells, and regulatory T cells (Tregs) are the main cell types applied to restore a tolerogenic immune status; MSCs play a more beneficial role due to their amenable properties and extensive cross-talks with different immune cells. With existing concerns about the employment of cells, new cell-free therapeutic paradigms, such as EV-based therapies, are gaining attention in this field. Additionally, EVs’ unique properties have made them to be known as smart immunomodulators and are considered as a potential substitute for cell therapy. This review provides an overview of the advantages and disadvantages of cell-based and EV-based methods for treating autoimmune diseases. The study also presents an outlook on the future of EVs to be implemented in clinics for autoimmune patients.

Hazeri, AH, Abouei Mehrizi, A, Mohseni, SS, Ebrahimi Warkiani, M & Razavi Bazaz, S 2023, 'A Novel Strategy for Square-Wave Micromixers: A Survey of RBC Lysis for Further Biological Analysis', Industrial & Engineering Chemistry Research, vol. 62, no. 40, pp. 16215-16224.
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He, J, Li, H, Mai, J, Ke, Y, Zhai, C, Li, JJ, Jiang, L, Shen, G & Ding, X 2023, 'Profiling extracellular vesicle surface proteins with 10 µL peripheral plasma within 4 h', Journal of Extracellular Vesicles, vol. 12, no. 9.
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AbstractExtracellular vesicle (EV) surface proteins, expressed by primary tumours, are important biomarkers for early cancer diagnosis. However, the detection of these EV proteins is complicated by their low abundance and interference from non‐EV components in clinical samples. Herein, we present a MEmbrane‐Specific Separation and two‐step Cascade AmpLificatioN (MESS2CAN) strategy for direct detection of EV surface proteins within 4 h. MESS2CAN utilises novel lipid probes (long chains linked by PEG2K with biotin at one end, and DSPE at the other end) and streptavidin‐coated magnetic beads, permitting a 49.6% EV recovery rate within 1 h. A dual amplification strategy with a primer exchange reaction (PER) cascaded by the Cas12a system then allows sensitive detection of the target protein at 10 EV particles per microliter. Using 4 cell lines and 90 clinical test samples, we demonstrate MESS2CAN for analysing HER2, EpCAM and EGFR expression on EVs derived from cells and patient plasma. MESS2CAN reports the desired specificity and sensitivity of EGFR (AUC = 0.98) and of HER2 (AUC = 1) for discriminating between HER2‐positive breast cancer, triple‐negative breast cancer and healthy donors. MESS2CAN is a pioneering method for highly sensitive in vitro EV diagnostics, applicable to clinical samples with trace amounts of EVs.

Hofer, OJ, Alsweiler, J, Tran, T & Crowther, CA 2023, 'Glycemic control in gestational diabetes and impact on biomarkers in women and infants', Pediatric Research, vol. 94, no. 2, pp. 466-476.
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Abstract Background Gestational diabetes mellitus (GDM) is linked to the dysregulation of inflammatory markers in women with GDM compared to women without. It is unclear whether the intensity of glycemic control influences these biomarkers. We aimed to assess whether different glycemic targets for women with GDM and compliance influence maternal and infant biomarkers. Methods Maternity hospitals caring for women with GDM were randomized in the TARGET Trial to tight or less tight glycemic targets. Maternal blood was collected at study entry, 36 weeks’ gestation, and 6 months postpartum, and cord plasma after birth. We assessed compliance to targets and concentrations of maternal serum and infant biomarkers. Results Eighty-two women and infants were included in the study. Concentrations of maternal and infant biomarkers did not differ between women assigned to tighter and less tight glycemic targets; however, concentrations were altered in maternal serum leptin and CRP and infant cord C-peptide, leptin, and IGF in women who complied with tighter targets. Conclusions Use of tighter glycemic targets in women with GDM does not change the concentrations of maternal and infant biomarkers compared to less tight targets. However, when compliance is achieved to tighter targets, maternal and infant biomarkers are altered. Impact The use of ti...

Holmes, NP, Roohani, I, Entezari, A, Guagliardo, P, Mirkhalaf, M, Lu, Z, Chen, Y-S, Yang, L, Dunstan, CR, Zreiqat, H & Cairney, JM 2023, 'Discovering an unknown territory using atom probe tomography: Elemental exchange at the bioceramic scaffold/bone tissue interface', Acta Biomaterialia, vol. 162, pp. 199-210.
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Honda, T, Tran, T, Popplestone, S, Draper, CE, Yousafzai, AK, Romero, L & Fisher, J 2023, 'Parents’ mental health and the social-emotional development of their children aged between 24 and 59 months in low-and middle-income countries: A systematic review and meta-analyses', SSM - Mental Health, vol. 3, pp. 100197-100197.
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Ho-Pham, LT, Nguyen, HG, Nguyen-Pham, SQ, Hoang, DK, Tran, TS & Nguyen, TV 2023, 'Longitudinal changes in bone mineral density during perimenopausal transition: the Vietnam Osteoporosis Study', Osteoporosis International, vol. 34, no. 8, pp. 1381-1387.
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Huang, Y, Du, Z, Bao, G, Fang, G, Cappadona, M, McClements, L, Tuch, BE, Lu, H & Xu, X 2023, 'Smart Drug-Delivery System of Upconversion Nanoparticles Coated with Mesoporous Silica for Controlled Release', Pharmaceutics, vol. 15, no. 1, pp. 89-89.
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Drug-delivery vehicles have garnered immense interest in recent years due to unparalleled progress made in material science and nanomedicine. However, the development of stimuli-responsive devices with controllable drug-release systems (DRSs) is still in its nascent stage. In this paper, we designed a two-way controlled drug-release system that can be promoted and prolonged, using the external stimulation of near-infrared light (NIR) and protein coating. A hierarchical nanostructure was fabricated using upconversion nanoparticles (UCNPs)—mesoporous silica as the core-shell structure with protein lysozyme coating. The mesoporous silica shell provides abundant pores for the loading of drug molecules and a specific type of photosensitive molecules. The morphology and the physical properties of the nanostructures were thoroughly characterized. The results exhibited the uniform core-shell nanostructures of ~four UCNPs encapsulated in one mesoporous silica nanoparticle. The core-shell nanoparticles were in the spherical shape with an average size of 200 nm, average surface area of 446.54 m2/g, and pore size of 4.6 nm. Using doxorubicin (DOX), a chemotherapy agent as the drug model, we demonstrated that a novel DRS with capacity of smart modulation to promote or inhibit the drug release under NIR light and protein coating, respectively. Further, we demonstrated the therapeutic effect of the designed DRSs using breast cancer cells. The reported novel controlled DRS with dual functionality could have a promising potential for chemotherapy treatment of solid cancers.

Jia, Z, Xu, X, Zhu, D & Zheng, Y 2023, 'Design, printing, and engineering of regenerative biomaterials for personalized bone healthcare', Progress in Materials Science, vol. 134, pp. 101072-101072.
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Kapellos, TS, Baßler, K, Fujii, W, Nalkurthi, C, Schaar, AC, Bonaguro, L, Pecht, T, Galvao, I, Agrawal, S, Saglam, A, Dudkin, E, Frishberg, A, de Domenico, E, Horne, A, Donovan, C, Kim, RY, Gallego-Ortega, D, Gillett, TE, Ansari, M, Schulte-Schrepping, J, Offermann, N, Antignano, I, Sivri, B, Lu, W, Eapen, MS, van Uelft, M, Osei-Sarpong, C, van den Berge, M, Donker, HC, Groen, HJM, Sohal, SS, Klein, J, Schreiber, T, Feißt, A, Yildirim, AÖ, Schiller, HB, Nawijn, MC, Becker, M, Händler, K, Beyer, M, Capasso, M, Ulas, T, Hasenauer, J, Pizarro, C, Theis, FJ, Hansbro, PM, Skowasch, D & Schultze, JL 2023, 'Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease', Cell Reports, vol. 42, no. 6, pp. 112525-112525.
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Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill defined. Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small-airway inflammation, emphysema, and severe breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased in early-stage COPD, and changes in molecular and functional neutrophil states correlate with lung function decline. Assessing neutrophils and their bone marrow precursors in a murine cigarette smoke exposure model identified similar molecular changes in blood neutrophils and precursor populations that also occur in the blood and lung. Our study shows that systemic molecular alterations in neutrophils and their precursors are part of early-stage COPD, a finding to be further explored for potential therapeutic targets and biomarkers for early diagnosis and patient stratification.

Kaur, P, Bohidar, HB, Nisbet, DR, Pfeffer, FM, Rifai, A, Williams, R & Agrawal, R 2023, 'Waste to high-value products: The performance and potential of carboxymethylcellulose hydrogels via the circular economy', Cellulose, vol. 30, no. 5, pp. 2713-2730.
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Krishnan, S, DeMaere, MZ, Beck, D, Ostrowski, M, Seymour, JR & Darling, AE 2023, 'Rhometa: Population recombination rate estimation from metagenomic read datasets', PLOS Genetics, vol. 19, no. 3, pp. e1010683-e1010683.
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Prokaryotic evolution is influenced by the exchange of genetic information between species through a process referred to as recombination. The rate of recombination is a useful measure for the adaptive capacity of a prokaryotic population. We introduce Rhometa (https://github.com/sid-krish/Rhometa), a new software package to determine recombination rates from shotgun sequencing reads of metagenomes. It extends the composite likelihood approach for population recombination rate estimation and enables the analysis of modern short-read datasets. We evaluated Rhometa over a broad range of sequencing depths and complexities, using simulated and real experimental short-read data aligned to external reference genomes. Rhometa offers a comprehensive solution for determining population recombination rates from contemporary metagenomic read datasets. Rhometa extends the capabilities of conventional sequence-based composite likelihood population recombination rate estimators to include modern aligned metagenomic read datasets with diverse sequencing depths, thereby enabling the effective application of these techniques and their high accuracy rates to the field of metagenomics. Using simulated datasets, we show that our method performs well, with its accuracy improving with increasing numbers of genomes. Rhometa was validated on a real S. pneumoniae transformation experiment, where we show that it obtains plausible estimates of the rate of recombination. Finally, the program was also run on ocean surface water metagenomic datasets, through which we demonstrate that the program works on uncultured metagenomic datasets.

Laval, H, Holmes, A, Marcus, MA, Watts, B, Bonfante, G, Schmutz, M, Deniau, E, Szymanski, R, Lartigau‐Dagron, C, Xu, X, Cairney, JM, Hirakawa, K, Awai, F, Kubo, T, Wantz, G, Bousquet, A, Holmes, NP & Chambon, S 2023, 'Toward High Efficiency Water Processed Organic Photovoltaics: Controlling the Nanoparticle Morphology with Surface Energies', Advanced Energy Materials, vol. 13, no. 26.
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AbstractHere efficient organic photovoltaic devices fabricated from water‐based colloidal dispersions with donor:acceptor composite nanoparticles achieving up to 9.98% power conversion efficiency (PCE) are reported. This high efficiency for water processed organic solar cells is attributed to morphology control by surface energy matching between the donor and the acceptor materials. Indeed, due to a low interfacial energy between donor and the acceptor, no large phase separation occurs during the nanoparticle formation process as well as upon thermal annealing. Indeed, synchrotron‐based scanning transmission X‐ray microscopy reveals that the internal morphology of composite nanoparticles is intermixed as well as the active layer morphology after thermal treatment. The PCE of this system reaches 85% that of devices prepared from chlorinated solvent. The gap between water‐based inks and organic solvent‐based inks gets narrower, which is promising for the development of eco‐friendly processing and fabrication of organic photovoltaics.

Li, D, Wang, G, Li, J, Yan, L, Liu, H, Jiu, J, Li, X, Li, JJ & Wang, B 2023, 'Biomaterials for Tissue-Engineered Treatment of Tendinopathy in Animal Models: A Systematic Review', Tissue Engineering Part B: Reviews, vol. 29, no. 4, pp. 387-413.
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Li, X, Li, D, Li, J, Wang, G, Yan, L, Liu, H, Jiu, J, Li, JJ & Wang, B 2023, 'Preclinical Studies and Clinical Trials on Cell-Based Treatments for Meniscus Regeneration', Tissue Engineering Part B: Reviews, vol. 29, no. 6, pp. 634-670.
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Li, X, Yan, L, Li, D, Fan, Z, Liu, H, Wang, G, Jiu, J, Yang, Z, Li, JJ & Wang, B 2023, 'Failure modes after anterior cruciate ligament reconstruction: a systematic review and meta-analysis', International Orthopaedics, vol. 47, no. 3, pp. 719-734.
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PURPOSE: The reason for graft failure after anterior cruciate ligament reconstruction (ACLR) is multifactorial. Controversies remain regarding the predominant factor and incidence of failure aetiology in the literature. This review aimed to provide a meta-analysis of the literature to evaluate the relative proportion of various failure modes among patients with ACLR failure. METHODS: The PubMed, Embase, Cochrane Library, Web of Science, and EBSCO databases were searched for literature on ACLR failure or revision from 1975 to 2021. Data related to causes for ACLR surgical failure were extracted, and a random effects model was used to pool the results, which incorporates potential heterogeneity. Failure modes were compared between different populations, research methods, graft types, femoral portal techniques, and fixation methods by subgroup analysis or linear regression. Funnel plots were used to identify publication bias and small-study effects. RESULTS: A total of 39 studies were analyzed, including 33 cohort studies and six registry-based studies reporting 6578 failures. The results showed that among patients with ACLR failure or revision, traumatic reinjury was the most common failure mode with a rate of 40% (95% CI: 35-44%), followed by technical error (34%, 95% CI: 28-42%) and biological failure (11%, 95% CI: 7-15%). Femoral tunnel malposition was the most common cause of the technical error (29%, 95% CI: 18-41%), with more than two times higher occurrence than tibial tunnel malposition (11%, 95% CI: 6-16%). Traumatic reinjury was the most common factor for ACLR failure in European populations and in recent studies, while technical errors were more common in Asian populations, earlier studies, and surgery performed using the transtibial (TT) portal technique. Biological factors were more likely to result in ACLR failure in hamstring (HT) autografts compared to bone-patellar tendon-bone (BPTB) autografts. CONCLUSION: Trauma is the most important fa...

Lin, G, Khan, JU, Zhand, S, Liu, Y & Jin, D 2023, 'Modular DNAzymes-Hydrogel Membrane Carriers for Highly Sensitive Isothermal Cross-Cascade Detection of Pathogenic Bacteria Nucleic Acids', Analytical Chemistry, vol. 95, no. 35, pp. 13353-13360.
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The increasing prevalence of antimicrobial resistance has called for improved diagnostic testing of pathogenic bacteria. However, the development of rapid, cost-effective, and easy-to-use tests for bacterial infections remains a constant challenge. Here, we report a class of modular hydrogel membrane carriers incorporated with composite DNAzymes, which enable rapid and highly sensitive detection of pathogenic bacteria gene target analytes. We apply free radical polymerization to incorporate composite DNAzymes, consisting of an RNA substrate component and a DNAzyme component (e.g., 10-23 or 8-17 DNAzymes), into polyethylene glycol diacrylate polymer networks. Initiated by a nucleic acid target acting as an assembly facilitator, multicomponent DNAzymes are combined to cleave the RNA substrate component in the hydrogel carriers, which releases the DNAzyme component to cleave RNA reporter probes to generate fluorescence. We modulate the morphology, composition, and microporous structures of the DNAzyme carriers to achieve quantitative assay performance. We demonstrate a rapid and high-sensitivity detection of C. trachomatis gene target analytes as low as 50 fM in a short assay time of 25 min. The work represents a crucial step forward in the development of a generic, isothermal, and protein enzyme-free pathogenic bacteria testing platform technology.

Liu, H, Yan, X, Jiu, J, Li, JJ, Zhang, Y, Wang, G, Li, D, Yan, L, Du, Y, Zhao, B & Wang, B 2023, 'Self-assembly of gelatin microcarrier-based MSC microtissues for spinal cord injury repair', Chemical Engineering Journal, vol. 451, pp. 138806-138806.
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Current approaches for treating spinal cord injury (SCI) are mainly based on cell transplantation. Mesenchymal stem cells (MSCs) can help slow the progression of SCI due to their trophic function. However, SCI creates a complex microenvironment that reduces cell activity and hence cellular function, ultimately resulting in poor therapeutic outcomes. To help maintain function in transplanted cells, we produced functional tissue constructs by self-assembly of MSC microtissues comprising of porous gelatin microcarriers (GM) and MSCs. These microtissues maintained cellular activity without incurring an excessive amount of apoptosis and delayed senescence in vitro. The paracrine function of MSCs also improved within microtissues, shown by the increased secretion of nerve regeneration-related factors. Microtissues were transplanted in a rat model of complete spinal cord transection, and therapeutic effects were evaluated through behavioral measurements, imaging, histology, and western blot analysis. RNA-seq of spinal cord tissues using Gene Ontology analysis further revealed that the microtissues may have induced repair in SCI through mechanisms related to neurotrophin-3 (NT-3) regulation of response mediator protein 2 (CRMP2) phosphorylation, and inhibition of inflammatory response through interleukin-17 (IL-17), Chemokine C-X-C motif Ligand 1 (CXCL1) axis. The gelatin microcarrier-based MSC microtissues we developed may be effective in providing a new treatment strategy for SCI.

Lotfi, M, Morshedi Rad, D, Mashhadi, SS, Ashouri, A, Mojarrad, M, Mozaffari-Jovin, S, Farrokhi, S, Hashemi, M, Lotfi, M, Ebrahimi Warkiani, M & Abbaszadegan, MR 2023, 'Recent Advances in CRISPR/Cas9 Delivery Approaches for Therapeutic Gene Editing of Stem Cells', Stem Cell Reviews and Reports, vol. 19, no. 8, pp. 2576-2596.
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Abstract Rapid advancement in genome editing technologies has provided new promises for treating neoplasia, cardiovascular, neurodegenerative, and monogenic disorders. Recently, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has emerged as a powerful gene editing tool offering advantages, including high editing efficiency and low cost over the conventional approaches. Human pluripotent stem cells (hPSCs), with their great proliferation and differentiation potential into different cell types, have been exploited in stem cell-based therapy. The potential of hPSCs and the capabilities of CRISPR/Cas9 genome editing has been paradigm-shifting in medical genetics for over two decades. Since hPSCs are categorized as hard-to-transfect cells, there is a critical demand to develop an appropriate and effective approach for CRISPR/Cas9 delivery into these cells. This review focuses on various strategies for CRISPR/Cas9 delivery in stem cells. Graphical Abstract

Mei, F, Li, JJ, Li, J, Dong, S, Li, Z & Xing, D 2023, 'Global Cluster Analysis and Network Visualization in Musculoskeletal Pain Management: A Scientometric Mapping', Orthopaedic Surgery, vol. 15, no. 1, pp. 301-314.
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ObjectiveMusculoskeletal pain is the most prominent clinical manifestation of more than 150 musculoskeletal disease conditions, and its effective long‐term management poses a great challenge to healthcare systems globally. For this, it is important to understand current research progress on musculoskeletal pain management. The purpose of the present study is to provide a comprehensive insight into the current state of research and global trends in musculoskeletal pain management.MethodsPublications on musculoskeletal pain management from 1972 to 2021 were retrieved from the Science Citation Index‐Expanded (SCIE) database. Included articles were any article type related to aspects of musculoskeletal pain management, including etiology, mechanisms, epidemiology, treatment, outcomes, side effects, and patient compliance. Publication data were analyzed using bibliometric methods. The software VOSviewer was employed to perform bibliographic coupling, co‐authorship, co‐citation, and co‐occurrence analysis, and to visualize publication tendencies in musculoskeletal pain management.ResultsA total of 5475 articles were included in this study. The number of global publications on musculoskeletal pain management has escalated annually. Based on the number of publications and citations from the published literature, as well as the H‐index, the United States led global contributions in this area. The institutions making the highest contributions were the League of European Research Universities (LERU), the University of Sydney, and Harvard University. The journal BMC Musculoskeletal Disorders published the highest number of articles in this area. The published studies fall under six groups: “Prevention and rehabilitation,” “Etiology and diagnosis,...

Mei, F, Li, JJ, Lin, J, Zhou, D & Xing, D 2023, 'Constrained Condylar Prostheses for the Treatment of Charcot Arthropathy: A Case Report and Literature Review', Orthopaedic Surgery, vol. 15, no. 5, pp. 1423-1430.
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BackgroundNeuroarthropathy of the knee or Charcot knee, leading to chronic joint destruction, is a rare disease that is difficult to diagnose. The treatment of this condition is difficult and controversial.Case PresentationA 74‐year‐old Asian woman has had bilateral knee pain for 22 years and deformity for 10 years, which has been aggravating for 2 months. Physical examination showed bilateral knee varus deformity greater than 15°, and −20 to 90° range of motion. X‐ray revealed bilateral varus deformity with massive free body hyperplasia. Combined with medical history as syringomyelia, the patient was diagnosed with bilateral Charcot knees and bilateral joint replacements were performed using Legacy Constrained Condylar Knee prostheses (LCCK; Zimmer, USA). The patient reported satisfactory treatment outcomes, pain relief, and improved range of motion in both knees, without postoperative complications or prosthesis loosening at 2 year after operation.ConclusionsTotal knee arthroplasty (TKA) may be considered a viable option for treating the Charcot knee. The use of constrained condylar prostheses can produce satisfactory results. Attention should be given to survival risks, complications, and other potential determining factors associated with TKA when devising a treatment strategy for the Charcot knee.

Miao, MZ, Su, QP, Cui, Y, Bahnson, EM, Li, G, Wang, M, Yang, Y, Collins, JA, Wu, D, Gu, Q, Chubinskaya, S, Diekman, BO, Yamada, KM & Loeser, RF 2023, 'Redox-active endosomes mediate α5β1 integrin signaling and promote chondrocyte matrix metalloproteinase production in osteoarthritis', Science Signaling, vol. 16, no. 809.
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Mechanical cues sensed by integrins induce cells to produce proteases to remodel the extracellular matrix. Excessive protease production occurs in many degenerative diseases, including osteoarthritis, in which articular cartilage degradation is associated with the genesis of matrix protein fragments that can activate integrins. We investigated the mechanisms by which integrin signals may promote protease production in response to matrix changes in osteoarthritis. Using a fragment of the matrix protein fibronectin (FN) to activate the α5β1 integrin in primary human chondrocytes, we found that endocytosis of the integrin and FN fragment complex drove the production of the matrix metalloproteinase MMP-13. Activation of α5β1 by the FN fragment, but not by intact FN, was accompanied by reactive oxygen species (ROS) production initially at the cell surface, then in early endosomes. These ROS-producing endosomes (called redoxosomes) contained the integrin-FN fragment complex, the ROS-producing enzyme NADPH oxidase 2 (NOX2), and SRC, a redox-regulated kinase that promotes MMP-13 production. In contrast, intact FN was endocytosed and trafficked to recycling endosomes without inducing ROS production. Articular cartilage from patients with osteoarthritis showed increased amounts of SRC and the NOX2 complex component p67 phox . Furthermore, we observed enhanced localization of SRC and p67 phox at early endosomes, suggesting that redoxosomes could transmit and sustain integrin signaling in response to matrix damage. This signaling mechanism not only amplifies the production of matrix-degrading proteases but also establishes a self-perpetuating cycle that contributes to the ongoing degradation of cartilage matrix in osteoarthritis.

Mirakhorli, F, Razavi Bazaz, S, Warkiani, ME & Ralph, PJ 2023, 'Ultra-high throughput microfluidic concentrator for harvesting of Tetraselmis sp. (Chlorodendrophyceae, Chlorophyta)', Algal Research, vol. 72, pp. 103145-103145.
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Mirzaeipoueinak, M, Mordechai, HS, Bangar, SS, Sharabi, M, Tipper, JL & Tavakoli, J 2023, 'Structure-function characterization of the transition zone in the intervertebral disc', Acta Biomaterialia, vol. 160, pp. 164-175.
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Moles, RJ, Perry, L, Naylor, JM, Center, J, Ebeling, P, Duque, G, Major, G, White, C, Yates, C, Jennings, M, Kotowicz, M, Tran, T, Bliuc, D, Si, L, Gibson, K, Basger, BJ, Bolton, P, Barnett, S, Hassett, G, Kelly, A, Bazarnik, B, Ezz, W, Luckie, K & Carter, SR 2023, 'Safer medicines To reduce falls and refractures for OsteoPorosis (#STOP): a study protocol for a randomised controlled trial of medical specialist-initiated pharmacist-led medication management reviews in primary care', BMJ Open, vol. 13, no. 8, pp. e072050-e072050.
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IntroductionMinimal trauma fractures (MTFs) often occur in older patients with osteoporosis and may be precipitated by falls risk-increasing drugs. One category of falls risk-increasing drugs of concern are those with sedative/anticholinergic properties. Collaborative medication management services such as Australia’s Home Medicine Review (HMR) can reduce patients’ intake of sedative/anticholinergics and improve continuity of care. This paper describes a protocol for an randomised controlled trial to determine the efficacy of an HMR service for patients who have sustained MTF.Method and analysisEligible participants are as follows: ≥65 years of age, using ≥5 medicines including at least one falls risk-increasing drug, who have sustained an MTF and under treatment in one of eight Osteoporosis Refracture Prevention clinics in Australia. Consenting participants will be randomised to control (standard care) or intervention groups. For the intervention group, medical specialists will refer to a pharmacist for HMR focused on reducing falls risk predominately through making recommendations to reduce falls risk medicines, and adherence to antiosteoporosis medicines. Twelve months from treatment allocation, comparisons between groups will be made. The main outcome measure is participants’ cumulative exposure to sedative and anticholinergics, using the Drug Burden Index. Secondary outcomes include medication adherence, emergency department visits, hospitalisations, falls and mortality. Economic evaluation will compare the intervention strategy with standard care.Ethics and disseminationApproval was obtained via the New South Wales Research Ethics and Governance Information System (approval number: 2021/ETH12003) with site-specific approvals granted through Human Research Ethics Committees for each...

Morshedi Rad, D, Hansen, WP, Zhand, S, Cranfield, C & Ebrahimi Warkiani, M 2023, 'A hybridized mechano-electroporation technique for efficient immune cell engineering', Journal of Advanced Research.
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Nazari, H, Shrestha, J, Naei, VY, Bazaz, SR, Sabbagh, M, Thiery, JP & Warkiani, ME 2023, 'Advances in TEER measurements of biological barriers in microphysiological systems', Biosensors and Bioelectronics, vol. 234, pp. 115355-115355.
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Newsom, ET, Sadeghpour, A, Entezari, A, Vinzons, JLU, Stanford, RE, Mirkhalaf, M, Chon, D, Dunstan, CR & Zreiqat, H 2023, 'Design and evaluation of 3D-printed Sr-HT-Gahnite bioceramic for FDA regulatory submission: A Good Laboratory Practice sheep study', Acta Biomaterialia, vol. 156, pp. 214-221.
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Nguyen, DT, Ho-Le, TP, Pham, L, Ho-Van, VP, Hoang, TD, Tran, TS, Frost, S & Nguyen, TV 2023, 'BONEcheck: A digital tool for personalized bone health assessment', Osteoporosis and Sarcopenia, vol. 9, no. 3, pp. 79-87.
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Ortega, JS, Corrales-Orovio, R, Ralph, P, Egaña, JT & Gentile, C 2023, 'Photosynthetic microorganisms for the oxygenation of advanced 3D bioprinted tissues', Acta Biomaterialia, vol. 165, pp. 180-196.
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3D bioprinting technology has emerged as a tool that promises to revolutionize the biomedical field, including tissue engineering and regeneration. Despite major technological advancements, several challenges remain to be solved before 3D bioprinted tissues could be fully translated from the bench to the bedside. As oxygen plays a key role in aerobic metabolism, which allows energy production in the mitochondria; as a consequence, the lack of tissue oxygenation is one of the main limitations of current bioprinted tissues and organs. In order to improve tissue oxygenation, recent approaches have been established for a broad range of clinical applications, with some already applied using 3D bioprinting technologies. Among them, the incorporation of photosynthetic microorganisms, such as microalgae and cyanobacteria, is a promising approach that has been recently explored to generate chimerical plant-animal tissues where, upon light exposure, oxygen can be produced and released in a localized and controlled manner. This review will briefly summarize the state-of-the-art approaches to improve tissue oxygenation, as well as studies describing the use of photosynthetic microorganisms in 3D bioprinting technologies. STATEMENT OF SIGNIFICANCE: 3D bioprinting technology has emerged as a tool for the generation of viable and functional tissues for direct in vitro and in vivo applications, including disease modeling, drug discovery and regenerative medicine. Despite the latest advancements in this field, suboptimal oxygen delivery to cells before, during and after the bioprinting process limits their viability within 3D bioprinted tissues. This review article first highlights state-of-the-art approaches used to improve oxygen delivery in bioengineered tissues to overcome this challenge. Then, it focuses on the emerging roles played by photosynthetic organisms as novel biomaterials for bioink generation. Finally, it provides considerations around current challenges...

Owen, B, Kechagidis, K, Bazaz, SR, Enjalbert, R, Essmann, E, Mallorie, C, Mirghaderi, F, Schaaf, C, Thota, K, Vernekar, R, Zhou, Q, Warkiani, ME, Stark, H & Krüger, T 2023, 'Lattice-Boltzmann modelling for inertial particle microfluidics applications - a tutorial review', Advances in Physics: X, vol. 8, no. 1.
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Pourhamzeh, M, Asadian, S, Mirzaei, H, Minaei, A, Shahriari, E, Shpichka, A, Es, HA, Timashev, P, Hassan, M & Vosough, M 2023, 'Novel antigens for targeted radioimmunotherapy in hepatocellular carcinoma', Molecular and Cellular Biochemistry, vol. 478, no. 1, pp. 23-37.
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Rabiee, N, Dokmeci, MR, Zarrabi, A, Makvandi, P, Saeb, MR, Karimi-Maleh, H, Jafarzadeh, S, Karaman, C, Yamauchi, Y, Warkiani, ME, Bencherif, SA, Mehta, G, Eguchi, M, Kaushik, A, Shahbazi, M-A, Paiva-Santos, AC, Ryl, J, Lima, EC, Hamblin, MR, Varma, RS, Huh, Y, Vilian, ATE, Gupta, PK, Lakhera, SK, Kesari, KK, Liu, Y-T, Tahriri, M, Rama Raju, GS, Adeli, M, Mohammadi, A, Wang, J, Ansari, MZ, Aminabhavi, T, Savoji, H, Sethi, G, Bączek, T, Kot-Wasik, A, Penoff, ME, Nafchi, AM, Kucinska-Lipka, J, Zargar, M, Asadnia, M, Aref, AR, Safarkhani, M, Ashrafizadeh, M, Umapathi, R, Ghasemi, A & Radisic, M 2023, 'Green Biomaterials : fundamental principles', Green Biomaterials, vol. 1, no. 1, pp. 1-4.
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Radfar, P, Ding, L, de la Fuente, LR, Aboulkheyr, H, Gallego-Ortega, D & Warkiani, ME 2023, 'Rapid metabolomic screening of cancer cells via high-throughput static droplet microfluidics', Biosensors and Bioelectronics, vol. 223, pp. 114966-114966.
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Effective isolation and in-depth analysis of Circulating Tumour Cells (CTCs) are greatly needed in diagnosis, prognosis and monitoring of the therapeutic response of cancer patients but have not been completely fulfilled by conventional approaches. The rarity of CTCs and the lack of reliable biomarkers to distinguish them from peripheral blood cells have remained outstanding challenges for their clinical implementation. Herein, we developed a high throughput Static Droplet Microfluidic (SDM) device with 38,400 chambers, capable of isolating and classifying the number of metabolically active CTCs in peripheral blood at single-cell resolution. Owing to the miniaturisation and compartmentalisation capability of our device, we first demonstrated the ability to precisely measure the lactate production of different types of cancer cells inside 125 pL droplets at single-cell resolution. Furthermore, we compared the metabolomic activity of leukocytes from healthy donors to cancer cells and showed the ability to differentiate them. To further prove the clinical relevance, we spiked cancer cell lines in human healthy blood and showed the possibility to detect the cancer cells from leukocytes. Lastly, we tested the workflow on 8 preclinical mammary mouse models including syngeneic 67NR (non-metastatic) and 4T1.2 (metastatic) models with Triple-Negative Breast Cancer (TNBC) as well as transgenic mouses (12-week-old MMTV-PyMT). The results have shown the ability to precisely distinguish metabolically active CTCs from the blood using the proposed SDM device. The workflow is simple and robust which can eliminate the need for specialised equipment and expertise required for single-cell analysis of CTCs and facilitate on-site metabolic screening of cancer cells.

Radfar, P, Ding, L, Es, HA & Warkiani, ME 2023, 'A Microfluidic Approach for Enrichment and Single-Cell Characterization of Circulating Tumor Cells from Peripheral Blood', pp. 141-150.
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Ramakrishna, VAS, Chamoli, U, Larosa, AG, Mukhopadhyay, SC, Gangadhara Prusty, B & Diwan, AD 2023, 'A biomechanical comparison of posterior fixation approaches in lumbar fusion using computed tomography based lumbosacral spine modelling', Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, vol. 237, no. 2, pp. 243-253.
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Extreme lateral interbody fusion (XLIF) may be performed with a standalone interbody cage, or with the addition of unilateral or bilateral pedicle screws; however, decisions regarding supplemental fixation are predominantly based on clinical indicators. This study examines the impact of posterior supplemental fixation on facet micromotions, cage loads and load-patterns at adjacent levels in a L4-L5 XLIF at early and late fusion stages. CT data from an asymptomatic subject were segmented into anatomical regions and digitally stitched into a surface mesh of the lumbosacral spine (L1-S1). The interbody cage and posterior instrumentation (unilateral and bilateral) were inserted at L4-L5. The volumetric mesh was imported into finite element software for pre-processing, running nonlinear static solves and post-processing. Loads and micromotions at the index-level facets reduced commensurately with the extent of posterior fixation accompanying the XLIF, while load-pattern changes observed at adjacent facets may be anatomically dependent. In flexion at partial fusion, compressive stress on the cage reduced by 54% and 72% in unilateral and bilateral models respectively; in extension the reductions were 58% and 75% compared to standalone XLIF. A similar pattern was observed at full fusion. Unilateral fixation provided similar stability compared to bilateral, however there was a reduction in cage stress-risers with the bilateral instrumentation. No changes were found at adjacent discs. Posterior supplemental fixation alters biomechanics at the index and adjacent levels in a manner that warrants consideration alongside clinical information. Unilateral instrumentation is a more efficient option where the stability requirements and subsidence risk are not excessive.

Ramakrishna, VAS, Chamoli, U, Mukhopadhyay, SC, Diwan, AD & Prusty, BG 2023, 'Measuring compressive loads on a ‘smart’ lumbar interbody fusion cage: Proof of concept', Journal of Biomechanics, vol. 147, pp. 111440-111440.
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Razavi Bazaz, S, Zhand, S, Salomon, R, Beheshti, EH, Jin, D & Warkiani, ME 2023, 'ImmunoInertial microfluidics: A novel strategy for isolation of small EV subpopulations', Applied Materials Today, vol. 30, pp. 101730-101730.
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Cancer-specific small extracellular vesicles (sEVs), known as exosomes, have shown a great promise to serve as novel biomarkers for cancer diagnosis and prognosis in liquid biopsies. However, the high heterogeneity of sEVs posed great technical challenges to acquiring their molecular information. A simple and reproducible method for isolating subpopulations of sEVs can significantly enhance the detection and stratification of these circulating biomarkers and their function. This study used the synergic effects of the immunoaffinity-based approach and inertial microfluidics (ImmunoInertial microfluidics) to isolate specific subpopulations of sEVs. At first, the cancer cell-derived sEVs were captured on microbeads of varying sizes which were functionalized with specific capture antibodies such as epithelial cell adhesion molecule (EpCAM), epidermal growth factor receptor (EGFR), and the programmed death-ligand 1 (PD-L1), facilitating the selective capture of sEVs. The sEVs-bearing microbeads were subsequently introduced to a series of inertial microfluidic channels, called iZExoSub (inertial zigzag microfluidics for exosome subpopulation separation), for size-based bead separation. Results revealed more than 90% efficiency in sEVs subpopulation separation, further proved via flow cytometry analysis data. Our approach is capable of selective isolation and quantitative detection of important biomarkers from sEVs subpopulations with high sensitivity and low cost and has the capacity to process samples of varying volumes, ranging from µL up to mL continuously. This system can outperform FACS machines in terms of sample throughput by orders of magnitudes. In addition, this study emphasized the necessity of using a consistent sEV marker (as capture and detector) across different samples for accurate assessment of subpopulations.

Rennie, C, Huang, Y, Siwakoti, P, Du, Z, Padula, M, Bao, G, Tuch, BE, Xu, X & McClements, L 2023, 'In vitroevaluation of a hybrid drug-delivery nanosystem for fibrosis prevention in cell therapy for Type 1 diabetes', Nanomedicine, vol. 18, no. 1, pp. 53-66.
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Background: Implantation of insulin-secreting cells has been trialed as a treatment for Type 1 diabetes mellitus; however, the host immunogenic response limits their effectiveness. Methodology: The authors developed a core-shell nanostructure of upconversion nanoparticle-mesoporous silica for controlled local delivery of an immunomodulatory agent, MCC950, using near-infrared light and validated it in in vitro models of fibrosis. Results: The individual components of the nanosystem did not affect the proliferation of insulin-secreting cells, unlike fibroblast proliferation (p < 0.01). The nanosystem is effective at releasing MCC950 and preventing fibroblast differentiation (p < 0.01), inflammation (IL-6 expression; p < 0.05) and monocyte adhesion (p < 0.01). Conclusion: This MCC950-loaded nanomedicine system could be used in the future together with insulin-secreting cell implants to increase their longevity as a curative treatment for Type 1 diabetes mellitus.

Roche, CD, Lin, H, Huang, Y, de Bock, CE, Beck, D, Xue, M & Gentile, C 2023, '3D bioprinted alginate-gelatin hydrogel patches containing cardiac spheroids recover heart function in a mouse model of myocardial infarction', Bioprinting, vol. 30, pp. e00263-e00263.
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Roohani, I, Entezari, A & Zreiqat, H 2023, 'Liquid crystal display technique (LCD) for high resolution 3D printing of triply periodic minimal surface lattices bioceramics', Additive Manufacturing, vol. 74, pp. 103720-103720.
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Sadeghirad, H, Bahrami, T, Layeghi, SM, Yousefi, H, Rezaei, M, Hosseini‐Fard, SR, Radfar, P, Warkiani, ME, O'Byrne, K & Kulasinghe, A 2023, 'Immunotherapeutic targets in non‐small cell lung cancer', Immunology, vol. 168, no. 2, pp. 256-272.
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AbstractNon‐small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and has a 5‐year survival rate of ~20%. Immunotherapies have shown promising results leading to durable responses, however, they are only effective for a subset of patients. To determine the best therapeutic approach, a thorough and in‐depth profiling of the tumour microenvironment (TME) is required. The TME is a complex network of cell types that form an interconnected network, promoting tumour cell initiation, growth and dissemination. The stroma, immune cells and endothelial cells that comprise the TME generate a plethora of cytotoxic or cytoprotective signalling pathways. In this review, we discuss immunotherapeutic targets in NSCLC tumours and how the TME may influence patients' response to immunotherapy.

Salis, Z, Gallego, B, Nguyen, TV & Sainsbury, A 2023, 'Association of Decrease in Body Mass Index With Reduced Incidence and Progression of the Structural Defects of Knee Osteoarthritis: A Prospective Multi‐Cohort Study', Arthritis & Rheumatology, vol. 75, no. 4, pp. 533-543.
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ObjectiveTo define the association between change in body mass index (BMI) and the incidence and progression of the structural defects of knee osteoarthritis as assessed by radiography.MethodsRadiographic analyses of knees at baseline and at 4–5 years of follow‐up were obtained from the following 3 independent cohort studies: the Osteoarthritis Initiative (OAI) study, the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study. Logistic regression analyses using generalized estimating equations, with clustering of both knees within individuals, were used to investigate the association between change in BMI from baseline to 4–5 years of follow‐up and the incidence and progression of knee osteoarthritis.ResultsA total of 9,683 knees (from 5,774 participants) in an “incidence cohort” and 6,075 knees (from 3,988 participants) in a “progression cohort” were investigated. Change in BMI was positively associated with both the incidence and progression of the structural defects of knee osteoarthritis. The adjusted odds ratio (OR) for osteoarthritis incidence was 1.05 (95% confidence interval [95% CI] 1.02–1.09), and the adjusted OR for osteoarthritis progression was 1.05 (95% CI 1.01–1.09). Change in BMI was also positively associated with degeneration (i.e., narrowing) of the joint space and with degeneration of the femoral and tibial surfaces (as indicated by osteophytes) on the medial but not on the lateral side of the knee.ConclusionA decrease in BMI was independently associated with lower odds of incidence and progression of the structural defects of knee osteoarthritis and could be a component in preventing the onset or worsening of knee osteoarthritis.

Seneviratne, JA, Carter, DR, Mittra, R, Gifford, A, Kim, PY, Luo, J, Mayoh, C, Salib, A, Rahmanto, AS, Murray, J, Cheng, NC, Nagy, Z, Wang, Q, Kleynhans, A, Tan, O, Sutton, SK, Xue, C, Chung, SA, Zhang, Y, Sun, C, Zhang, L, Haber, M, Norris, MD, Fletcher, JI, Liu, T, Dilda, PJ, Hogg, PJ, Cheung, BB & Marshall, GM 2023, 'Inhibition of mitochondrial translocase SLC25A5 and histone deacetylation is an effective combination therapy in neuroblastoma', International Journal of Cancer, vol. 152, no. 7, pp. 1399-1413.
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AbstractThe mitochondrion is a gatekeeper of apoptotic processes, and mediates drug resistance to several chemotherapy agents used to treat cancer. Neuroblastoma is a common solid cancer in young children with poor clinical outcomes following conventional chemotherapy. We sought druggable mitochondrial protein targets in neuroblastoma cells. Among mitochondria‐associated gene targets, we found that high expression of the mitochondrial adenine nucleotide translocase 2 (SLC25A5/ANT2), was a strong predictor of poor neuroblastoma patient prognosis and contributed to a more malignant phenotype in pre‐clinical models. Inhibiting this transporter with PENAO reduced cell viability in a panel of neuroblastoma cell lines in a TP53‐status‐dependant manner. We identified the histone deacetylase inhibitor, suberanilohydroxamic acid (SAHA), as the most effective drug in clinical use against mutant TP53 neuroblastoma cells. SAHA and PENAO synergistically reduced cell viability, and induced apoptosis, in neuroblastoma cells independent of TP53‐status. The SAHA and PENAO drug combination significantly delayed tumour progression in pre‐clinical neuroblastoma mouse models, suggesting that these clinically advanced inhibitors may be effective in treating the disease.

Shahriari Felordi, M, Alikhani, M, Farzaneh, Z, Alipour Choshali, M, Ebrahimi, M, Aboulkheyr Es, H, Piryaei, A, Najimi, M & Vosough, M 2023, '(‐)‐Epigallocatechin‐3‐gallate induced apoptosis by dissociation of c‐FLIP/Ku70 complex in gastric cancer cells', Journal of Cellular and Molecular Medicine, vol. 27, no. 17, pp. 2572-2582.
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AbstractAnti‐cancer properties of (‐)‐epigallocatechin‐3‐gallate (EGCG) are mediated via apoptosis induction, as well as inhibition of cell proliferation and histone deacetylase. Accumulation of stabilized cellular FLICE‐inhibitory protein (c‐FLIP)/Ku70 complex in the cytoplasm inhibits apoptosis through interruption of extrinsic apoptosis pathway. In this study, we evaluated the anti‐cancer role of EGCG in gastric cancer (GC) cells through dissociation of c‐FLIP/Ku70 complex. MKN‐45 cells were treated with EGCG or its antagonist MG149 for 24 h. Apoptosis was evaluated by flow cytometry and quantitative RT‐PCR. Protein expression of c‐FLIP and Ku70 was analysed using western blot and immunofluorescence. Dissociation of c‐FLIP/Ku70 complex as well as Ku70 translocation were studied by sub‐cellular fractionation and co‐immunoprecipitation. EGCG induced apoptosis in MKN‐45 cells with substantial up‐regulation of P53 and P21, down‐regulation of c‐Myc and Cyclin D1 as well as cell cycle arrest in S and G2/M check points. Moreover, EGCG treatment suppressed the expression of c‐FLIP and Ku70, decreased their interaction while increasing the Ku70 nuclear content. By dissociating the c‐FLIP/Ku70 complex, EGCG could be an alternative component to the conventional HDAC inhibitors in order to induce apoptosis in GC cells. Thus, its combination with other cancer therapy protocols could result in a better therapeutic outcome.

Sharon, SE, Aharonov, A, Mordechai, HS, Tavakoli, J & Sharabi, M 2023, 'Collagen-Based Micro/Nano Fibrous Constructs: Step-By-Step Reverse Biomimetics of Structure and Mechanical Function', ACS Applied Polymer Materials, vol. 5, no. 4, pp. 2816-2829.
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Sheu, A, Blank, RD, Tran, T, Bliuc, D, Greenfield, JR, White, CP & Center, JR 2023, 'Associations of Type 2 Diabetes, Body Composition, and Insulin Resistance with Bone Parameters: The Dubbo Osteoporosis Epidemiology Study', JBMR Plus, vol. 7, no. 9.
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ABSTRACTType 2 diabetes (T2D) may be associated with increased risk of fractures, despite preserved bone mineral density (BMD). Obesity and insulin resistance (IR) may have separate effects on bone turnover and bone strength, which contribute to skeletal fragility. We characterized and assessed the relative associations of obesity, body composition, IR, and T2D on bone turnover markers (BTMs), BMD, and advanced hip analysis (AHA). In this cross‐sectional analysis of Dubbo Osteoporosis Epidemiology Study, 525 (61.3% women) participants were grouped according to T2D, IR (homeostasis model assessment insulin resistance [HOMA‐IR] </≥2.5), and BMI (</≥25 kg/m2): insulin‐sensitive lean (IS‐L), insulin‐sensitive overweight/obese (IS‐O), insulin‐resistant (IR), and T2D. BMD, AHA, and body composition, including visceral adipose tissue (VAT) (on dual‐energy x‐ray absorptiometry scan) and fasting BTMs, were assessed. Analyses performed using Bayesian model averaging and principal component analysis. T2D was associated with low BTMs (by 26%–30% [95% confidence interval [CI] 11%–46%] in women, 35% [95% CI 18%–48%] in men compared to IS‐L), which persisted after adjustment for VAT. BTMs were similar among IR/IS‐O/IS‐L. BMD was similar among T2D/IR/IS‐O; BMD was low only in IS‐L. All groups were similar after adjustment for BMI. Similarly, AHA components were lowest in IS‐L (attenuated following adjustment). On multivariate analysis, T2D was independently associated with BTMs. IR was also associated with C‐terminal telopeptide of type 1 collagen in men. Age and body size were the strongest independent contributors to BMD and AHA. VAT was inversely associated with section modulus, cross‐sectional area, cross‐sectional moment of inertia in women, and hip axis length in men. Low bone turnover is associated with T2D and IR (in men), while BMD and hip strength/geometry are predominantly associated with body size....

Sheu, A, O’Connell, RL, Jenkins, AJ, Tran, T, Drury, PL, Sullivan, DR, Li, L, Colman, P, O’Brien, R, Kesäniemi, YA, Center, JR, White, CP & Keech, AC 2023, 'Factors associated with fragility fractures in type 2 diabetes: An analysis of the randomised controlled Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study', Diabetes/Metabolism Research and Reviews, vol. 39, no. 5.
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AbstractAimsFracture risk is elevated in some type 2 diabetes patients. Bone fragility may be associated with more clinically severe type 2 diabetes, although prospective studies are lacking. It is unknown which diabetes‐related characteristics are independently associated with fracture risk. In this post‐hoc analysis of fracture data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial (ISRCTN#64783481), we hypothesised that diabetic microvascular complications are associated with bone fragility.Materials and MethodsThe FIELD trial randomly assigned 9795 type 2 diabetes participants (aged 50–75 years) to receive oral co‐micronised fenofibrate 200 mg (n = 4895) or placebo (n = 4900) daily for a median of 5 years. We used Cox proportional hazards models to identify baseline sex‐specific diabetes‐related parameters independently associated with incident fractures.ResultsOver 49,470 person‐years, 137/6138 men experienced 141 fractures and 143/3657 women experienced 145 fractures; incidence rates for the first fracture of 4∙4 (95% CI 3∙8–5∙2) and 7∙7 per 1000 person‐years (95% CI 6∙5–9∙1), respectively. Fenofibrate had no effect on fracture outcomes. In men, baseline macrovascular disease (HR 1∙52, 95% CI 1∙05–2∙21, p = 0∙03), insulin use (HR 1∙62, HR 1∙03–2∙55, p = 0∙03), and HDL‐cholesterol (HR 2∙20, 95% CI 1∙11–4∙36, p = 0∙02) were independently associated with fracture. In women, independent risk factors included baseline peripheral neuropathy (HR 2∙04, 95% CI 1∙16–3∙59, p = 0∙01) and insulin use (HR 1∙55, 95% CI 1∙02–2∙33, p = 0∙04).

Shokouhian, B, Negahdari, B, Heydari, Z, Totonchi, M, Aboulkheyr Es, H, Piryaei, A, Mostafavi, E & Vosough, M 2023, 'HNF4α is possibly the missing link between epithelial–mesenchymal transition and Warburg effect during hepatocarcinogenesis', Cancer Science, vol. 114, no. 4, pp. 1337-1352.
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AbstractHepatocellular carcinoma (HCC) is a heterogeneous, late‐diagnosed, and highly recurrent malignancy that often affects the whole body's metabolism. Finding certain theranostic molecules that can address current concerns simultaneously is one of the priorities in HCC management. In this study, performing protein–protein interaction network analysis proposed hepatocyte nuclear factor 4 alpha (HNF4α) as a hub protein, associating epithelial–mesenchymal transition (EMT) to reprogrammed cancer metabolism, formerly known as the Warburg effect. Both phenomena improved the compensation of cancerous cells in competitive conditions. Mounting evidence has demonstrated that HNF4α is commonly downregulated and serves as a tumor suppressor in the HCC. Enhancing the HNF4α mRNA translation through a specific synthetic antisense long non‐coding RNA, profoundly affects both EMT and onco‐metabolic modules in HCC cells. HNF4α overexpression decreased featured mesenchymal transcription factors and improved hepatocytic function, decelerated glycolysis, accelerated gluconeogenesis, and improved dysregulated cholesterol metabolism. Moreover, HNF4α overexpression inhibited the migration, invasion, and proliferation of HCC cells and decreased metastasis rate and tumor growth in xenografted nude mice. Our findings suggest a central regulatory role for HNF4α through its broad access to a wide variety of gene promoters involved in EMT and the Warburg effect in human hepatocytes. This essential impact indicates that HNF4α may be a potential target for HCC treatment.

Shrestha, J, Paudel, KR, Nazari, H, Dharwal, V, Bazaz, SR, Johansen, MD, Dua, K, Hansbro, PM & Warkiani, ME 2023, 'Advanced models for respiratory disease and drug studies', Medicinal Research Reviews, vol. 43, no. 5, pp. 1470-1503.
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AbstractThe global burden of respiratory diseases is enormous, with many millions of people suffering and dying prematurely every year. The global COVID‐19 pandemic witnessed recently, along with increased air pollution and wildfire events, increases the urgency of identifying the most effective therapeutic measures to combat these diseases even further. Despite increasing expenditure and extensive collaborative efforts to identify and develop the most effective and safe treatments, the failure rates of drugs evaluated in human clinical trials are high. To reverse these trends and minimize the cost of drug development, ineffective drug candidates must be eliminated as early as possible by employing new, efficient, and accurate preclinical screening approaches. Animal models have been the mainstay of pulmonary research as they recapitulate the complex physiological processes, Multiorgan interplay, disease phenotypes of disease, and the pharmacokinetic behavior of drugs. Recently, the use of advanced culture technologies such as organoids and lung‐on‐a‐chip models has gained increasing attention because of their potential to reproduce human diseased states and physiology, with clinically relevant responses to drugs and toxins. This review provides an overview of different animal models for studying respiratory diseases and evaluating drugs. We also highlight recent progress in cell culture technologies to advance integrated models and discuss current challenges and present future perspectives.

Siwakoti, P, Rennie, C, Huang, Y, Li, JJ, Tuch, BE, McClements, L & Xu, X 2023, 'Challenges with Cell-based Therapies for Type 1 Diabetes Mellitus', Stem Cell Reviews and Reports, vol. 19, no. 3, pp. 601-624.
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Type 1 diabetes (T1D) is a chronic, lifelong metabolic disease. It is characterised by the autoimmune-mediated loss of insulin-producing pancreatic β cells in the islets of Langerhans (β-islets), resulting in disrupted glucose homeostasis. Administration of exogenous insulin is the most common management method for T1D, but this requires lifelong reliance on insulin injections and invasive blood glucose monitoring. Replacement therapies with beta cells are being developed as an advanced curative treatment for T1D. Unfortunately, this approach is limited by the lack of donated pancreatic tissue, the difficulties in beta cell isolation and viability maintenance, the longevity of the transplanted cells in vivo, and consequently high costs. Emerging approaches to address these limitations are under intensive investigations, including the production of insulin-producing beta cells from various stem cells, and the development of bioengineered devices including nanotechnologies for improving islet transplantation efficacy without the need for recipients taking toxic anti-rejection drugs. These emerging approaches present promising prospects, while the challenges with the new techniques need to be tackled for ultimately clinical treatment of T1D. This review discussed the benefits and limitations of the cell-based therapies for beta cell replacement as potential curative treatment for T1D, and the applications of bioengineered devices including nanotechnology to overcome the challenges associated with beta cell transplantation.

Smith, MAA, Khot, MI, Taccola, S, Fry, NR, Muhonen, PL, Tipper, JL, Jayne, DG, Kay, RW & Harris, RA 2023, 'A digitally driven manufacturing process for high resolution patterning of cell formations', Biomedical Microdevices, vol. 25, no. 2.
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AbstractThis paper presents the engineering and validation of an enabling technology that facilitates new capabilities in in vitro cell models for high-throughput screening and tissue engineering applications. This is conducted through a computerized system that allows the design and deposition of high-fidelity microscale patterned coatings that selectively alter the chemical and topographical properties of cell culturing surfaces. Significantly, compared to alternative methods for microscale surface patterning, this is a digitally controlled and automated process thereby allowing scientists to rapidly create and explore an almost infinite range of cell culture patterns. This new capability is experimentally validated across six different cell lines demonstrating how the precise microscale deposition of these patterned coatings can influence spatiotemporal growth and movement of endothelial, fibroblast, neuronal and macrophage cells. To further demonstrate this platform, more complex patterns are then created and shown to guide the behavioral response of colorectal carcinoma cells. Graphical Abstract

Song, W, Ma, Z, Wang, X, Wang, Y, Wu, D, Wang, C, He, D, Kong, L, Yu, W, Li, JJ, Li, H & He, Y 2023, 'Macroporous Granular Hydrogels Functionalized with Aligned Architecture and Small Extracellular Vesicles Stimulate Osteoporotic Tendon‐To‐Bone Healing', Advanced Science, vol. 10, no. 34.
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AbstractOsteoporotic tendon‐to‐bone healing (TBH) after rotator cuff repair (RCR) is a significant orthopedic challenge. Considering the aligned architecture of the tendon, inflammatory microenvironment at the injury site, and the need for endogenous cell/tissue infiltration, there is an imminent need for an ideal scaffold to promote TBH that has aligned architecture, ability to modulate inflammation, and macroporous structure. Herein, a novel macroporous hydrogel comprising sodium alginate/hyaluronic acid/small extracellular vesicles from adipose‐derived stem cells (sEVs) (MHA‐sEVs) with aligned architecture and immunomodulatory ability is fabricated. When implanted subcutaneously, MHA‐sEVs significantly improve cell infiltration and tissue integration through its macroporous structure. When applied to the osteoporotic RCR model, MHA‐sEVs promote TBH by improving tendon repair through macroporous aligned architecture while enhancing bone regeneration by modulating inflammation. Notably, the biomechanical strength of MHA‐sEVs is approximately two times higher than the control group, indicating great potential in reducing postoperative retear rates. Further cell‐hydrogel interaction studies reveal that the alignment of microfiber gels in MHA‐sEVs induces tenogenic differentiation of tendon‐derived stem cells, while sEVs improve mitochondrial dysfunction in M1 macrophages (Mφ) and inhibit Mφ polarization toward M1 via nuclear factor‐kappaB (NF‐κb) signaling pathway. Taken together, MHA‐sEVs provide a promising strategy for future clinical application in promoting osteoporotic TBH.

Stratton-Powell, AA, Williams, S, Tipper, JL, Redmond, AC & Brockett, CL 2023, 'Isolation and characterisation of wear debris surrounding failed total ankle replacements', Acta Biomaterialia, vol. 159, pp. 410-422.
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Su, Z, Diao, T, McGuire, H, Yao, C, Yang, L, Bao, G, Xu, X, He, B & Zheng, Y 2023, 'Nanomaterials Solutions for Contraception: Concerns, Advances, and Prospects', ACS Nano, vol. 17, no. 21, pp. 20753-20775.
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Su, Z, Yao, C, Tipper, J, Yang, L, Xu, X, Chen, X, Bao, G, He, B, Xu, X & Zheng, Y 2023, 'Nanostrategy of Targeting at Embryonic Trophoblast Cells Using CuO Nanoparticles for Female Contraception', ACS Nano, vol. 17, no. 24, pp. 25185-25204.
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Effective contraceptives have been comprehensively adopted by women to prevent the negative consequences of unintended pregnancy for women, families, and societies. With great contributions of traditional hormonal drugs and intrauterine devices (IUDs) to effective female contraception by inhibiting ovulation and deactivating sperm, their long-standing side effects on hormonal homeostasis and reproductive organs for females remain concerns. Herein, we proposed a nanostrategy for female contraceptives, inducing embryonic trophoblast cell death using nanoparticles to prevent embryo implantation. Cupric oxide nanoparticles (CuO NPs) were adopted in this work to verify the feasibility of the nanostrategy and its contraceptive efficacy. We carried out the in vitro assessment on the interaction of CuO NPs with trophoblast cells using the HTR8/SVneo cell line. The results showed that the CuO NPs were able to be preferably uptaken into cells and induced cell damage via a variety of pathways including oxidative stress, mitochondrial damage, DNA damage, and cell cycle arrest to induce cell death of apoptosis, ferroptosis, and cuproptosis. Moreover, the key regulatory processes and the key genes for cell damage and cell death caused by CuO NPs were revealed by RNA-Seq. We also conducted in vivo experiments using a rat model to examine the contraceptive efficacy of both the bare CuO NPs and the CuO/thermosensitive hydrogel nanocomposite. The results demonstrated that the CuO NPs were highly effective for contraception. There was no sign of disrupting the homeostasis of copper and hormone, or causing inflammation and organ damage in vivo. In all, this nanostrategy exhibited huge potential for contraceptive development with high biosafety, efficacy, clinical translation, nonhormonal style, and on-demand for women.

Subramanian, S, Thoms, JAI, Huang, Y, Cornejo-Páramo, P, Koch, FC, Jacquelin, S, Shen, S, Song, E, Joshi, S, Brownlee, C, Woll, PS, Chacon-Fajardo, D, Beck, D, Curtis, DJ, Yehson, K, Antonenas, V, O'Brien, T, Trickett, A, Powell, JA, Lewis, ID, Pitson, SM, Gandhi, MK, Lane, SW, Vafaee, F, Wong, ES, Göttgens, B, Alinejad-Rokny, H, Wong, JWH & Pimanda, JE 2023, 'Genome-wide transcription factor–binding maps reveal cell-specific changes in the regulatory architecture of human HSPCs', Blood, vol. 142, no. 17, pp. 1448-1462.
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Abstract Hematopoietic stem and progenitor cells (HSPCs) rely on a complex interplay among transcription factors (TFs) to regulate differentiation into mature blood cells. A heptad of TFs (FLI1, ERG, GATA2, RUNX1, TAL1, LYL1, LMO2) bind regulatory elements in bulk CD34+ HSPCs. However, whether specific heptad-TF combinations have distinct roles in regulating hematopoietic differentiation remains unknown. We mapped genome-wide chromatin contacts (HiC, H3K27ac, HiChIP), chromatin modifications (H3K4me3, H3K27ac, H3K27me3) and 10 TF binding profiles (heptad, PU.1, CTCF, STAG2) in HSPC subsets (stem/multipotent progenitors plus common myeloid, granulocyte macrophage, and megakaryocyte erythrocyte progenitors) and found TF occupancy and enhancer-promoter interactions varied significantly across cell types and were associated with cell-type–specific gene expression. Distinct regulatory elements were enriched with specific heptad-TF combinations, including stem-cell–specific elements with ERG, and myeloid- and erythroid-specific elements with combinations of FLI1, RUNX1, GATA2, TAL1, LYL1, and LMO2. Furthermore, heptad-occupied regions in HSPCs were subsequently bound by lineage-defining TFs, including PU.1 and GATA1, suggesting that heptad factors may prime regulatory elements for use in mature cell types. We also found that enhancers with cell-type–specific heptad occupancy shared a common grammar with respect to TF binding motifs, suggesting that combinatorial binding of TF complexes was at least partially regulated by features encoded in DNA sequence motifs. Taken together, this study comprehensively characterizes the gene regulatory landscape in rare subpopulations of human HSPCs. The accompanying data sets should serve as a valuable resource for understanding adult hematopoiesis and a framework for analyzing aberrant regulatory networks in leukemic cells.

Tai, M-R, Ji, H-W, Chen, J-P, Liu, X-F, Song, B-B, Zhong, S-Y, Rifai, A, Nisbet, DR, Barrow, CJ, Williams, RJ & Li, R 2023, 'Biomimetic triumvirate nanogel complexes via peptide-polysaccharide-polyphenol self-assembly', International Journal of Biological Macromolecules, vol. 251, pp. 126232-126232.
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Tavakoli, J, Diwan, AD & Tipper, JL 2023, 'Intervertebral disc-on-a-chip: a precision engineered toolbox for low back pain studies', Trends in Biotechnology, vol. 41, no. 11, pp. 1339-1342.
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Tran, T, Ho-Le, T, Bliuc, D, Abrahamsen, B, Hansen, L, Vestergaard, P, Center, JR & Nguyen, TV 2023, '‘Skeletal Age’ for mapping the impact of fracture on mortality', eLife, vol. 12, p. e83888.
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Background:Fragility fracture is associated with an increased risk of mortality, but mortality is not part of doctor-patient communication. Here, we introduce a new concept called ‘Skeletal Age’ as the age of an individual’s skeleton resulting from a fragility fracture to convey the combined risk of fracture and fracture-associated mortality for an individual.Methods:We used the Danish National Hospital Discharge Register which includes the whole-country data of 1,667,339 adults in Denmark born on or before January 1, 1950, who were followed up to December 31, 2016 for incident low-trauma fracture and mortality. Skeletal age is defined as the sum of chronological age and the number of years of life lost (YLL) associated with a fracture. Cox’s proportional hazards model was employed to determine the hazard of mortality associated with a specific fracture for a given risk profile, and the hazard was then transformed into YLL using the Gompertz law of mortality.Results:During the median follow-up period of 16 years, there had been 307,870 fractures and 122,744 post-fracture deaths. A fracture was associated with between 1 and 7 years of life lost, with the loss being greater in men than women. Hip fractures incurred the greatest loss of life years. For instance, a 60-year-old individual with a hip fracture is estimated to have a skeletal age of 66 for men and 65 for women. Skeletal Age was estimated for each age and fracture site stratified by gender.Conclusions:We propose ‘Skeletal Age’ as a new metric to assess the impact of a fragility fracture on an individual’s life expectancy. This approach will enhance doctor-patient risk communication about the risks associated with osteoporosis.

Tran, TS, Ho-Le, TP, Bliuc, D, Center, JR, Blank, RD & Nguyen, TV 2023, 'Prevention of Hip Fractures: Trade-off between Minor Benefits to Individuals and Large Benefits to the Community', Journal of Bone and Mineral Research, vol. 38, no. 11, pp. 1594-1602.
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ABSTRACT Goeffrey Rose postulated that a population-based measure bringing a small benefit to each individual can yield large benefits to the community. We aimed to test this axiom by quantifying the relationship between change in bone mineral density (BMD) and hip fracture incidence between two prospective cohorts separated by ~10 years. In this prospective population-based Dubbo Osteoporosis Epidemiology Study (DOES), the participants aged 60+ were recruited in two waves: the initial cohort (1311 women, 842 men) in 1989 to 1992 and the second cohort (974 women, 544 men) in 1999 to 2001. The incident hip fracture was radiologically ascertained. Femoral neck BMD was measured biannually. Multivariable-adjusted Cox's proportional hazards models were adjusted for the predefined covariates such as age, BMI, lifestyle factors, falls, and prior fracture. Compared with the initial cohort, the second cohort had a higher femoral neck BMD by ~0.04 g/cm2 in women and 0.03 g/cm2 in men. However, the prevalence of osteoporosis in the second cohort was halved (prevalence ratio 0.51, 95% CI 0.36 to 0.73 in women; 0.45, 0.24 to 0.84 in men), and its hip fracture incidence was significantly reduced (hazard ratio 0.54, 95% CI, 0.38 to 0.78 in women; 0.39, 0.19 to 0.80 in men). Sensitivity analyses indicated that the “effect” was unlikely due to unmeasured confounders. These findings suggest that a population-wide strategy aimed at enhancing BMD across the entire population could lead to a substantial decrease in the incidence of hip fractures. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Vasilescu, SA, Ding, L, Parast, FY, Nosrati, R & Warkiani, ME 2023, 'Sperm quality metrics were improved by a biomimetic microfluidic selection platform compared to swim-up methods', Microsystems & Nanoengineering, vol. 9, no. 1, p. 37.
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AbstractSperm selection is an essential component of all assisted reproductive treatments (ARTs) and is by far the most neglected step in the ART workflow in regard to technological innovation. Conventional sperm selection methodologies typically produce a higher total number of sperm with variable motilities, morphologies, and levels of DNA integrity. Gold-standard techniques, including density gradient centrifugation (DGC) and swim-up (SU), have been shown to induce DNA fragmentation through introducing reactive oxygen species (ROS) during centrifugation. Here, we demonstrate a 3D printed, biologically inspired microfluidic sperm selection device (MSSP) that utilizes multiple methods to simulate a sperms journey toward selection. Sperm are first selected based on their motility and boundary-following behavior and then on their expression of apoptotic markers, yielding over 68% more motile sperm than that of previously reported methods with a lower incidence of DNA fragmentation and apoptosis. Sperm from the MSSP also demonstrated higher motile sperm recovery after cryopreservation than that of SU or neat semen. Experiments were conducted side-by-side against conventional SU methods using human semen (n = 33) and showed over an 85% improvement in DNA integrity with an average 90% reduction in sperm apoptosis. These results that the platform is easy-to-use for sperm selection and mimics the biological function of the female reproductive tract during conception.

Wang, Y, Douville, C, Cohen, JD, Mattox, A, Curtis, S, Silliman, N, Popoli, M, Ptak, J, Dobbyn, L, Nehme, N, Dudley, JC, Summers, M, Zhang, M, Ho-Pham, LT, Tran, BNH, Tran, TS, Nguyen, TV, Bettegowda, C, Papadopoulos, N, Kinzler, KW & Vogelstein, B 2023, 'Detection of rare mutations, copy number alterations, and methylation in the same template DNA molecules', Proceedings of the National Academy of Sciences, vol. 120, no. 15.
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The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy number are the most sensitive ways to detect the presence of cancer. To further increase the sensitivity of such assays with limited amounts of sample, it would be useful to be able to evaluate the same template molecules for all these changes. Here, we report an approach, called MethylSaferSeqS, that achieves this goal, and can be applied to any standard library preparation method suitable for massively parallel sequencing. The innovative step was to copy both strands of each DNA-barcoded molecule with a primer that allows the subsequent separation of the original strands (retaining their 5-methylcytosine residues) from the copied strands (in which the 5-methylcytosine residues are replaced with unmodified cytosine residues). The epigenetic and genetic alterations present in the DNA molecules can then be obtained from the original and copied strands, respectively. We applied this approach to plasma from 265 individuals, including 198 with cancers of the pancreas, ovary, lung, and colon, and found the expected patterns of mutations, copy number alterations, and methylation. Furthermore, we could determine which original template DNA molecules were methylated and/or mutated. MethylSaferSeqS should be useful for addressing a variety of questions relating genetics and epigenetics.

Yaghoubi Naei, V, Bordhan, P, Mirakhorli, F, Khorrami, M, Shrestha, J, Nazari, H, Kulasinghe, A & Ebrahimi Warkiani, M 2023, 'Advances in novel strategies for isolation, characterization, and analysis of CTCs and ctDNA', Therapeutic Advances in Medical Oncology, vol. 15.
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Over the past decade, the detection and analysis of liquid biopsy biomarkers such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have advanced significantly. They have received recognition for their clinical usefulness in detecting cancer at an early stage, monitoring disease, and evaluating treatment response. The emergence of liquid biopsy has been a helpful development, as it offers a minimally invasive, rapid, real-time monitoring, and possible alternative to traditional tissue biopsies. In resource-limited settings, the ideal platform for liquid biopsy should not only extract more CTCs or ctDNA from a minimal sample volume but also accurately represent the molecular heterogeneity of the patient’s disease. This review covers novel strategies and advancements in CTC and ctDNA-based liquid biopsy platforms, including microfluidic applications and comprehensive analysis of molecular complexity. We discuss these systems’ operational principles and performance efficiencies, as well as future opportunities and challenges for their implementation in clinical settings. In addition, we emphasize the importance of integrated platforms that incorporate machine learning and artificial intelligence in accurate liquid biopsy detection systems, which can greatly improve cancer management and enable precision diagnostics.

Yam, AO, Bailey, J, Lin, F, Jakovija, A, Youlten, SE, Counoupas, C, Gunzer, M, Bald, T, Woodruff, TM, Triccas, JA, Goldstein, LD, Gallego-Ortega, D, Grey, ST & Chtanova, T 2023, 'Neutrophil Conversion to a Tumor-Killing Phenotype Underpins Effective Microbial Therapy', Cancer Research, vol. 83, no. 8, pp. 1315-1328.
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AbstractThe inflammatory microenvironment of solid tumors creates a protumorigenic milieu that resembles chronic inflammation akin to a subverted wound healing response. Here, we investigated the effect of converting the tumor microenvironment from a chronically inflamed state to one of acute microbial inflammation by injecting microbial bioparticles directly into tumors. Intratumoral microbial bioparticle injection led to rapid and dramatic changes in the tumor immune composition, the most striking of which was a substantial increase in the presence of activated neutrophils. In situ photoconversion and intravital microscopy indicated that tumor neutrophils transiently switched from sessile producers of VEGF to highly motile neutrophils that clustered to make neutrophil-rich domains in the tumor. The neutrophil clusters remodeled tumor tissue and repressed tumor growth. Single-cell transcriptional analysis of microbe-stimulated neutrophils showed a profound shift in gene expression towards heightened activation and antimicrobial effector function. Microbe-activated neutrophils also upregulated chemokines known to regulate neutrophil and CD8+ T-cell recruitment. Microbial therapy also boosted CD8+ T-cell function and enhanced the therapeutic benefit of checkpoint inhibitor therapy in tumor-bearing mice and provided protection in a model of tumor recurrence. These data indicate that one of the major effector mechanisms of microbial therapy is the conversion of tumor neutrophils from a wound healing to an acutely activated cytotoxic phenotype, highlighting a rationale for broader deployment of microbial therapy in the treatment of solid cancers.Significance:Intratumoral injection of microbial bioparticles stimulates neutrophil antitumor functions, suggesting pathways for optimizing efficacy of microbial therapies and paving the way for th...

Yan, L, Ge, L, Dong, S, Saluja, K, Li, D, Reddy, KS, Wang, Q, Yao, L, Li, JJ, Roza da Costa, B, Xing, D & Wang, B 2023, 'Evaluation of Comparative Efficacy and Safety of Surgical Approaches for Total Hip Arthroplasty', JAMA Network Open, vol. 6, no. 1, pp. e2253942-e2253942.
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ImportanceEach approach for primary total hip arthroplasty (THA) has a long learning curve, so a surgeon’s choice to change their preferred approach needs to be guided by clear justifications. However, current evidence does not suggest that any of the THA approaches are more beneficial than others, and the choice of approach is mainly based on the knowledge and experience of the surgeon and individual patient characteristics.ObjectiveTo assess the efficacy and safety associated with different surgical approaches for THA.Data SourcesA comprehensive search of PubMed, EMBASE, and Cochrane databases from inception to March 26, 2022; reference lists of eligible trials; and related reviews.Study SelectionRandomized clinical trials (RCTs) comparing different surgical approaches, including the 2-incision approach, direct anterior approach (DAA), direct lateral approach (DLA), minimally invasive direct lateral approach (MIS-DLA), minimally invasive anterolateral approach (MIS-ALA), posterior approach (PA), minimally invasive posterior approach (MIS-PA), and supercapsular percutaneously assisted total hip arthroplasty (SuperPath), for primary THA.Data Extraction and SynthesisFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 2 reviewers independently extracted data on study participants, interventions, and outcomes as well as assessed the risk of bias using the Cochrane risk of bias tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. A frequentist framework was used to infor...

Yang, Z, Li, H, Lin, J, Xing, D, Li, JJ, Cribbin, EM, M. Kim, A, He, Z, Li, H, Guo, W, Zhang, L & Lin, J 2023, 'Research landscape of 3D printing in bone regeneration and bone repair: A bibliometric and visualized analysis from 2012 to 2022', International Journal of Bioprinting, vol. 9, no. 4, pp. 0-0.
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Three-dimensional printing (3DP) is a popular manufacturing technique with versatile potential for materials processing in tissue engineering and regenerative medicine. In particular, the repair and regeneration of significant bone defects remain as substantial clinical challenges that require biomaterial implants to maintain mechanical strength and porosity, which may be realized using 3DP. The rapid progress in 3DP development in the past decade warrants a bibliometric analysis to gain insights into its applications in bone tissue engineering (BTE). Here, we performed a comparative study using bibliometric methods for 3DP in bone repair and regeneration. A total of 2,025 articles were included, and the results showed an increase in the number of publications and relative research interest on 3DP annually worldwide. China was the leader in international cooperation in this field and also the largest contributor to the number of citations. The majority of articles in this field were published in the journal Biofabrication. Chen Y was the author who made the highest contribution to the included studies. The keywords included in the publications were mainly related to BTE and regenerative medicine (including &ldquo;3DP techniques,&rdquo; &ldquo;3DP materials,&rdquo; &ldquo;bone regeneration strategies,&rdquo; and &ldquo;bone disease therapeutics&rdquo;) for bone regeneration and repair. This bibliometric and visualized analysis provides significant insights into the historical development of 3DP in BTE from 2012 to 2022, which will be beneficial for scientists to conduct further investigations into this dynamic field.&nbsp;

Yang, Z, Wang, B, Liu, W, Li, X, Liang, K, Fan, Z, Li, JJ, Niu, Y, He, Z, Li, H, Wang, D, Lin, J, Du, Y, Lin, J & Xing, D 2023, 'In situ self-assembled organoid for osteochondral tissue regeneration with dual functional units', Bioactive Materials, vol. 27, pp. 200-215.
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Zanker, J, Scott, D, Alajlouni, D, Kirk, B, Bird, S, DeBruin, D, Vogrin, S, Bliuc, D, Tran, T, Cawthon, P, Duque, G & Center, JR 2023, 'Mortality, falls and slow walking speed are predicted by different muscle strength and physical performance measures in women and men', Archives of Gerontology and Geriatrics, vol. 114, pp. 105084-105084.
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Zhand, S, Zhu, Y, Nazari, H, Sadraeian, M, Warkiani, ME & Jin, D 2023, 'Correction to “Thiolate DNAzymes on Gold Nanoparticles for Isothermal Amplification and Detection of Mesothelioma-derived Exosomal PD-L1 mRNA”', Analytical Chemistry, vol. 95, no. 32, pp. 12193-12193.
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Zhand, S, Zhu, Y, Nazari, H, Sadraeian, M, Warkiani, ME & Jin, D 2023, 'Thiolate DNAzymes on Gold Nanoparticles for Isothermal Amplification and Detection of Mesothelioma-derived Exosomal PD-L1 mRNA', Analytical Chemistry, vol. 95, no. 6, pp. 3228-3237.
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Catalytic DNAzymes have been used for isothermal amplification and rapid detection of nucleic acids, holding the potential for point-of-care testing applications. However, when Subzymes (universal substrate and DNAzyme) are tethered to the polystyrene magnetic microparticles via biotin-streptavidin bonds, the residual free Subzymes are often detached from the microparticle surface, which causes a significant degree of false positives. Here, we attached dithiol-modified Subzyme to gold nanoparticle and improved the limit of detection (LoD) by 200 times compared to that using magnetic microparticles. As a proof of concept, we applied our new method for the detection of exosomal programed cell-death ligand 1 (PD-L1) RNA. As the classical immune checkpoint, molecule PD-L1, found in small extracellular vesicles (sEVs, traditionally called exosomes), can reflect the antitumor immune response for predicting immunotherapy response. We achieved the LoD as low as 50 fM in detecting both the RNA homologous to the PD-L1 gene and exosomal PD-L1 RNAs extracted from epithelioid and nonepithelioid subtypes of mesothelioma cell lines, which only takes 8 min of reaction time. As the first application of isothermal DNAzymes for detecting exosomal PD-L1 RNA, this work suggests new point-of-care testing potentials toward clinical translations.

Zhao, YC, Zhang, Y, Wang, Z, Jiang, F, Kyanian, K, Aye, S, Hong, T, Vatankhah, P, Nasser, A, Sun, A, Moldovan, L, Su, QP, Cho, A, Wang, Y, Passam, F, Ang, T & Ju, LA 2023, 'Novel Movable Typing for Personalized Vein‐Chips in Large Scale: Recapitulate Patient‐Specific Virchow's Triad and its Contribution to Cerebral Venous Sinus Thrombosis', Advanced Functional Materials, vol. 33, no. 23.
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AbstractThe Vein‐Chip recapitulates CVST Virchow's triad and enables systematic characterization of venous thrombogenesis with respect to fibrin formation and platelet aggregation. Distinct from the arterial setting, platelets universally adhere across the entire CVS Vein‐Chip independent of stenotic geometry and flow disturbance. Intriguingly, fibrin propagates along with the flow direction, but exclusively deposits to the inner vessel wall. Upon inflammatory endothelial injury, fibrin deposition mirrors to the outer vessel wall, but still not in the lumen. Together, the Vein‐Chip promises future applications for personalized thrombotic assessment and monitoring.

Zhao, YC, Zhang, Y, Wang, Z, Jiang, F, Kyanian, K, Aye, S, Hong, T, Vatankhah, P, Nasser, A, Sun, A, Moldovan, L, Su, QP, Cho, A, Wang, Y, Passam, F, Ang, T & Ju, LA 2023, 'Novel Movable Typing for Personalized Vein‐Chips in Large Scale: Recapitulate Patient‐Specific Virchow's Triad and its Contribution to Cerebral Venous Sinus Thrombosis (Adv. Funct. Mater. 23/2023)', Advanced Functional Materials, vol. 33, no. 23.
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Caderno, PV, Awaysheh, FM, Colino-Sanguino, Y, Fuente, LRDL, Valdes-Mora, F, Cabaleiro, JC, Pena, TF & Gallego-Ortega, D 1970, 'OPERA-gSAM: Big Data Processing Framework for UMI Sequencing at High Scalability and Efficiency', 2023 IEEE/ACM 23rd International Symposium on Cluster, Cloud and Internet Computing Workshops (CCGridW), 2023 IEEE/ACM 23rd International Symposium on Cluster, Cloud and Internet Computing Workshops (CCGridW), IEEE.
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De Dios, K, Ngoc, H, Tran, TS, Center, JR & Nguyen, TV 1970, 'Contribution of fat mass and obesity-associated (FTO) gene to osteoporosis phenotypes', JOURNAL OF BONE AND MINERAL RESEARCH, WILEY, pp. 256-256.

Gentile, C 1970, 'Abstract P1117: Personalized Care Using Patient-derived Cardiac Spheroids For Heart Failure Patients', Circulation Research, Ovid Technologies (Wolters Kluwer Health).
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Preclinical studies using currently available in vitro and in vivo models fail at fully recapitulating the in vivo human heart microenvironment and its pathophysiology, limiting their translation from the bench to the bedside. Our laboratory has developed cardiac spheroids (CSs) as advanced in vitro models of the human heart using cardiac myocytes, endothelial cells and fibroblasts at ratios approximating the ones found in the human heart. Thanks to patient-derived induced pluripotent stem cells (iPSCs), we have quickly moved to personalized CSs to establish advanced pathophysiological in vitro models of heart failure (HF). CSs have been used to evaluate short- and long-term effects of ischaemic/reperfusion (I/R) injury typical of myocardial infarction (MI), drug-induced toxicity, SARS-CoV-2 exposure and pregnancy-induced HF. This was achieved using our established protocols to induce I/R-mimic injury, as well by exposing CSs to doxorubicin (DOX), SARS-CoV-2 virus and pre-eclampsia blood samples, respectively. First, our analyses of cell toxicity ratios using calcein-AM and ethidium homodimer (staining live and dead cells, respectively) demonstrated treatment-specific loss in cell viability and increase in cell death compared to control (untreated, healthy) CSs. Other CSs stained with ethidium homodimer and cell-specific antibodies were imaged and further used for 3D rendering analyses using IMARIS software. This enabled us to identify cell-specific responses in each pathological condition. Then, our measurements of fractional shortening and contraction frequency in CSs showed a statistically significant loss of contractile function in treated CSs compared to controls. Finally, new ...

Ho-Le, TP, Tran, TS, Nguyen, HG, Center, JR, Eisman, JA & Nguyen, TV 1970, 'Genetic Prediction of Lifetime Risk of Fracture', The Journal of Clinical Endocrinology & Metabolism, WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, The Endocrine Society, Florence, ITALY, pp. e1403-e1412.
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Abstract Context Fragility fracture is a significant public health problem because it is associated with increased mortality. We want to find out whether the risk of fracture can be predicted from the time of birth. Objective To examine the association between a polygenic risk score (PRS) and lifetime fracture risk. Methods This population-based prospective study involved 3515 community-dwelling individuals aged 60+ years who have been followed for up to 20 years. Femoral neck bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry. A PRS was created by summing the weighted number of risk alleles for each single nucleotide polymorphism using BMD-associated coefficients. Fragility fractures were radiologically ascertained, whereas mortality was ascertained through a state registry. Residual lifetime risk of fracture (RLRF) was estimated by survival analysis. Results The mortality-adjusted RLRF for women and men was 36% (95% CI, 34%-39%) and 21% (18%-24%), respectively. Individuals with PRS &gt; 4.24 (median) had a greater risk (1.2-fold in women and 1.1-fold in men) than the population average risk. For hip fracture, the average RLRF was 10% (95% CI, 8%-12%) for women and ∼5% (3%-7%) for men; however, the risk was significantly increased by 1.5-fold and 1.3-fold for women and men with high PRS, respectively. Conclusion ...

Radfar, P, Ding, L, Oh, S & Warkiani, ME 1970, 'BIODEGRADABLE AND CUSTOMISED MICROCARRIERS FOR EFFICIENT AND SCALABLE CULTURE OF ADHERENT CELLS', CYTOTHERAPY, ELSEVIER SCI LTD, pp. S198-S199.

Richards, C, Rad, DM, Zhand, S, Warkiani, M & McClements, L 1970, 'EVALUATING GENE DELIVERY TECHNOLOGIES TO INVESTIGATE THE ROLE OF FKBPL IN TROPHOBLAST FUNCTION AND THE THERAPEUTIC POTENTIAL OF MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES', PLACENTA, Annual Meeting of the International-Federation-of-Placenta-Associations (IFPA), W B SAUNDERS CO LTD, NEW ZEALAND, Rotorua, pp. E49-E49.

Zhang, Y, Dong, L, Yang, G, Li, JJ & Wang, B 1970, 'Accelerated Aging Test Method of Lithium-Ion Batteries Featured with Aging Feature Reconstruction', 2023 IEEE 3rd International Conference on Industrial Electronics for Sustainable Energy Systems (IESES), 2023 IEEE 3rd International Conference on Industrial Electronics for Sustainable Energy Systems (IESES), IEEE.
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Cartland, SP, Patil, M, Boccanfuso, L, Kelland, E, Patrick, R, Manuneedhi Cholan, P, Su, P, Alwis, I, Ganss, R, Harvey, RP, Griffith, TS, Powell, J, Patel, S & Kavurma, MM 2023, 'Abstract 597: TRAIL-TRAIL-R Ligation Regulates EC-pericyte Crosstalk To Generate Stable Microvessel Networks In Ischemia', Ovid Technologies (Wolters Kluwer Health).
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Endothelial cell (EC)-pericyte crosstalk is essential for generating stable capillary networks. Capillary function and development is disrupted in CVD, and processes mediating this are poorly understood. TNF-related apoptosis-inducing ligand (TRAIL) stimulates blood vessel development in pre-clinical models, while circulating levels are suppressed in CVD patients. The contribution of EC-specific TRAIL to angiogenesis in ischemia is unknown. To address this, an EC-specific TRAIL knockout ( Trail EC-/- ) was generated. Compared to Trail EC+/+ , Trail EC-/- mice had ~60% reduction in plasma TRAIL, revealing the endothelium as a significant source of TRAIL in the healthy circulation. Angiogenesis was quantified in the Matrigel plug, aortic sprouting and hindlimb ischemia (HLI) models. EC/pericyte content in plugs were ~50-60% less in Trail EC-/- than Trail EC+/+ mice, with a ~50% reduction in mRNA expression of angiogenesis/pericyte markers. Trail EC-/- aortic segments had reduced microvascular sprouts in hypoxia, and ECs lacking TRAIL had an impaired ability to form tubules and recruit pericytes. CD31 + SMA + microvessel numbers (measure of EC-pericyte interaction) were signif...

Colino-Sanguino, Y, de la Fuente, LR, Gloss, B, Law, AMK, Handler, K, Pajic, M, Salomon, R, Gallego-Ortega, D & Valdes-Mora, F 2023, 'Performance comparison of high throughput single-cell RNA-Seq platforms in complex tissues', Cold Spring Harbor Laboratory.
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Entezari, A, Wu, Q, Mirkhalaf, M, Lu, Z, Roohani, I, Li, Q, Dunstan, C, Jiang, X & Zreiqat, H 2023, 'Unraveling the Influence of Pore Size and Shape in 3D Printed Ceramic Scaffolds on Osteogenesis', Elsevier BV.
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Ghorbanpour, S, Richards, C, Cole, L, McGrath, K, Warkiani, ME & McClements, L 2023, 'New 3D multicellular models of placental tissue for studying important mechanisms of preeclampsia', Elsevier BV, pp. e6-e6.
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Ghorbanpour, S, Richards, C, Pienaar, D, Sesperez, K, Aboulkheyr Es, H, Nikolic, V, Karadzov-Orlic, N, Mikovic, Z, Stefanovic, M, Cakic, Z, Alqudah, A, Cole, L, Gorrie, C, Mcgrath, K, Kavurma, MM, Warkiani, ME & McClements, L 2023, 'SC3_3. FKBPL signalling in placental development and preeclampsia', Elsevier BV, pp. e77-e78.
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Goss, DM, Vasilescu, SA, Vasilescu, PA, Cooke, S, Kim, SHK, Sacks, GP, Gardner, DK & Warkiani, ME 2023, 'AI facilitated sperm detection in azoospermic samples for use in ICSI', Cold Spring Harbor Laboratory.
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Hashmi, A, Hutvagner, G & Sidhu, S 2023, 'B-288 The Beginning of the End: AGO2 Protein Identified and Validated as a Novel Biomarker for Multi-cancer Diagnosis Through Bioinformatics Analysis and Immunoassay', Oxford University Press (OUP).
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Abstract Background Despite significant progress in cancer research, the complexity and heterogeneity of the disease still pose major challenges to accurate diagnosis and effective treatment. Recent advancements in biomedical technologies have led to the identification of reliable potential cancer biomarkers. In this sense, the link between microRNAs (master regulators of gene expression) & cancer is well-established, but there has been little research on the microRNA machinery itself. We aim to investigate whether changes in the expression of genes & proteins involved in the miRNA pathway can be used for multi-cancer detection. Method We analyzed RNASeq data from the TCGA (The Cancer Genome Atlas) and GTEX (The Genotype-Tissue Expression) projects to compare the expression of core components in the miRNA biogenesis pathway, including AGO2, DGCR8, XPO5, RAN, DROSHA, DICER, and TARBP2, in normal and tumorous samples across 22 tissue types, including adrenocortical, AML, breast, colon, lung, liver, esophageal, prostate, pancreas, stomach, thyroid, rectum, uterus and ovarian cancer. We accessed and analyzed the TCGA and GTEx datasets using the UCSC Xena Browser. We also measured the protein concentrations of all these microRNA regulators in 15 normal adrenal cortex, 15 benign adenoma, and 15 adrenocortical cancer tissue homogenate samples using commercial ELISA kits. The Human Protein Argonaute-2 (EIF2C2) ELISA Kit-AE45910HU (Abebio-Co.Ltd) was used for the assay procedure, which was performed according to the manufacturer’s instructions. Statistical analysis was performed using GraphPad Prism, Version 9 (GraphPad Software, CA, USA). A P-value of less than 0.05 was considered statistically significant....

Ju, L, Wang, H, Vatankhah, P, Wang, Y, Russel, B, Su, Q, Zhou, Z, Cox, C & Jin, J 2023, 'Microscale geometrical modulation of PIEZO1 mediated cell mechanosensing via cytoskeletal redistribution buckle', Research Square Platform LLC.
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Mei, F, Li, JJ, Lin, J, Xing, D & Dong, S 2023, 'Multidimensional characteristics of musculoskeletal pain and risk of hip fractures among elderly adults: The first longitudinal evidence from CHARLS', Research Square Platform LLC.
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Nguyen, DT, Ho-Le, TP, Pham, L, Ho-Van, VP, Hoang, TD, Tran, TS, Frost, S & Nguyen, TV 2023, 'BONEcheck: a digital tool for personalized bone health assessment', Cold Spring Harbor Laboratory.
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Nguyen, HD, Phung, AHT, Do, TC, Nguyen, QHN, Tran, TS, Nguyen, TV & Ho-Pham, LT 2023, 'Association of lifestyle factors and breast cancer risk in Vietnamese women: A matched case-control study', Research Square Platform LLC.
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Nguyen, HG, Nguyen, HT, Nguyen, LTT, Tran, TS, Ho-Pham, LT, Ling, SH & Nguyen, TV 2023, 'Identification of asymptomatic vertebral compression fracture using a novel shape-based algorithm', Research Square Platform LLC.
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Owen, B, Kechagidis, K, Bazaz, SR, Enjalbert, R, Essmann, E, Mallorie, C, Mirghaderi, F, Schaaf, C, Thota, K, Vernekar, R, Zhou, Q, Warkiani, ME, Stark, H & Krüger, T 2023, 'Lattice-Boltzmann Modelling for Inertial Particle Microfluidics Applications — A Tutorial Review', Cold Spring Harbor Laboratory.
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Richards, C, Rad, DM, Zhand, S, Warkiani, M & McClements, L 2023, 'Evaluating gene delivery technologies to investigate the role of FKBPL in trophoblast function and the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles', Elsevier BV, pp. e48-e49.
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Shrestha, J, Paudel, KR, Nazari, H, Dharwal, V, Bazaz, SR, Johansen, MD, Dua, K, Hansbro, PM & Warkiani, ME 2023, 'Front Cover Image, Volume 43, Issue 5', Wiley, pp. i-i.
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Tong, A, Kuchroo, M, Gupta, S, Venkat, A, San Juan, BP, Rangel, L, Zhu, B, Lock, JG, Chaffer, CL & Krishnaswamy, S 2023, 'Learning transcriptional and regulatory dynamics driving cancer cell plasticity using neural ODE-based optimal transport', Cold Spring Harbor Laboratory.
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