Displaying publications 1 - 20 of 68 in total

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  1. Fulltext Recent Outcomes and Challenges of Artificial Intelligence, Machine Learning, and Deep Learning in Neurosurgery
    Awuah WA, Adebusoye FT, Wellington J, David L, Salam A, Weng Yee AL, et al.
    World Neurosurg X, 2024 Jul;23:100301.
    PMID: 38577317 DOI: 10.1016/j.wnsx.2024.100301
    Neurosurgeons receive extensive technical training, which equips them with the knowledge and skills to specialise in various fields and manage the massive amounts of information and decision-making required throughout the various stages of neurosurgery, including preoperative, intraoperative, and postoperative care and recovery. Over the past few years, artificial intelligence (AI) has become more useful in neurosurgery. AI has the potential to improve patient outcomes by augmenting the capabilities of neurosurgeons and ultimately improving diagnostic and prognostic outcomes as well as decision-making during surgical procedures. By incorporating AI into both interventional and non-interventional therapies, neurosurgeons may provide the best care for their patients. AI, machine learning (ML), and deep learning (DL) have made significant progress in the field of neurosurgery. These cutting-edge methods have enhanced patient outcomes, reduced complications, and improved surgical planning.
  2. Fulltext Exploring the current landscape of single-cell RNA sequencing applications in gastric cancer research
    Awuah WA, Roy S, Tan JK, Adebusoye FT, Qiang Z, Ferreira T, et al.
    J Cell Mol Med, 2024 Apr;28(7):e18159.
    PMID: 38494861 DOI: 10.1111/jcmm.18159
    Gastric cancer (GC) represents a major global health burden and is responsible for a significant number of cancer-related fatalities. Its complex nature, characterized by heterogeneity and aggressive behaviour, poses considerable challenges for effective diagnosis and treatment. Single-cell RNA sequencing (scRNA-seq) has emerged as an important technique, offering unprecedented precision and depth in gene expression profiling at the cellular level. By facilitating the identification of distinct cell populations, rare cells and dynamic transcriptional changes within GC, scRNA-seq has yielded valuable insights into tumour progression and potential therapeutic targets. Moreover, this technology has significantly improved our comprehension of the tumour microenvironment (TME) and its intricate interplay with immune cells, thereby opening avenues for targeted therapeutic strategies. Nonetheless, certain obstacles, including tumour heterogeneity and technical limitations, persist in the field. Current endeavours are dedicated to refining protocols and computational tools to surmount these challenges. In this narrative review, we explore the significance of scRNA-seq in GC, emphasizing its advantages, challenges and potential applications in unravelling tumour heterogeneity and identifying promising therapeutic targets. Additionally, we discuss recent developments, ongoing efforts to overcome these challenges, and future prospects. Although further enhancements are required, scRNA-seq has already provided valuable insights into GC and holds promise for advancing biomedical research and clinical practice.
  3. Fulltext Unraveling the Behavior of Intrinsically Disordered Protein c-Myc: A Study Utilizing Gaussian-Accelerated Molecular Dynamics
    Gunasinghe KKJ, Rahman T, Chee Wezen X
    ACS Omega, 2024 Jan 16;9(2):2250-2262.
    PMID: 38250404 DOI: 10.1021/acsomega.3c05822
    The protein c-Myc is a transcription factor that remains largely intrinsically disordered and is known to be involved in various biological processes and is overexpressed in various cancers, making it an attractive drug target. However, intrinsically disordered proteins such as c-Myc do not show funnel-like basins in their free-energy landscapes; this makes their druggability a challenge. For the first time, we propose a heterodimer model of c-Myc/Max in full length in this work. We used Gaussian-accelerated molecular dynamics (GaMD) simulations to explore the behavior of c-Myc and its various regions, including the transactivation domain (TAD) and the basic helix-loop-helix-leucine-zipper (bHLH-Zipper) motif in three different conformational states: (a) monomeric c-Myc, (b) c-Myc when bound to its partner protein, Max, and (c) when Max was removed after binding. We analyzed the GaMD trajectories using root-mean-square deviation (RMSD), radius of gyration, root-mean-square fluctuation, and free-energy landscape (FEL) calculations to elaborate the behaviors of these regions. The results showed that the monomeric c-Myc structure showed a higher RMSD fluctuation as compared with the c-Myc/Max heterodimer in the bHLH-Zipper motif. This indicated that the bHLH-Zipper motif of c-Myc is more stable when it is bound to Max. The TAD region in both monomeric and Max-bound states showed similar plasticity in terms of RMSD. We also conducted residue decomposition calculations and showed that the c-Myc and Max interaction could be driven mainly by electrostatic interactions and the residues Arg299, Ile403, and Leu420 seemed to play important roles in the interaction. Our work provides insights into the behavior of c-Myc and its regions that could support the development of drugs that target c-Myc and other intrinsically disordered proteins.
  4. Antioxidant, anti-inflammatory and epigenetic potential of curcumin in Alzheimer's disease
    Abdul-Rahman T, Awuah WA, Mikhailova T, Kalmanovich J, Mehta A, Ng JC, et al.
    Biofactors, 2024 Jan 16.
    PMID: 38226733 DOI: 10.1002/biof.2039
    Alzheimer's disease (AD) constitutes a multifactorial neurodegenerative pathology characterized by cognitive deterioration, personality alterations, and behavioral shifts. The ongoing brain impairment process poses significant challenges for therapeutic interventions due to activating multiple neurotoxic pathways. Current pharmacological interventions have shown limited efficacy and are associated with significant side effects. Approaches focusing on the early interference with disease pathways, before activation of broad neurotoxic processes, could be promising to slow down symptomatic progression of the disease. Curcumin-an integral component of traditional medicine in numerous cultures worldwide-has garnered interest as a promising AD treatment. Current research indicates that curcumin may exhibit therapeutic potential in neurodegenerative pathologies, attributed to its potent anti-inflammatory and antioxidant properties. Additionally, curcumin and its derivatives have demonstrated an ability to modulate cellular pathways via epigenetic mechanisms. This article aims to raise awareness of the neuroprotective properties of curcuminoids that could provide therapeutic benefits in AD. The paper provides a comprehensive overview of the neuroprotective efficacy of curcumin against signaling pathways that could be involved in AD and summarizes recent evidence of the biological efficiency of curcumins in vivo.
  5. 3D printing in surgery: revolutionizing trauma and fracture care in low and middle-income countries
    Awuah WA, Tenkorang PO, Adebusoye FT, Ng JC, Wellington J, Abdul-Rahman T, et al.
    Postgrad Med J, 2023 Dec 21;100(1179):1-3.
    PMID: 37857514 DOI: 10.1093/postmj/qgad100
  6. The molecular landscape of neurological disorders: insights from single-cell RNA sequencing in neurology and neurosurgery
    Awuah WA, Ahluwalia A, Ghosh S, Roy S, Tan JK, Adebusoye FT, et al.
    Eur J Med Res, 2023 Nov 16;28(1):529.
    PMID: 37974227 DOI: 10.1186/s40001-023-01504-w
    Single-cell ribonucleic acid sequencing (scRNA-seq) has emerged as a transformative technology in neurological and neurosurgical research, revolutionising our comprehension of complex neurological disorders. In brain tumours, scRNA-seq has provided valuable insights into cancer heterogeneity, the tumour microenvironment, treatment resistance, and invasion patterns. It has also elucidated the brain tri-lineage cancer hierarchy and addressed limitations of current models. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis have been molecularly subtyped, dysregulated pathways have been identified, and potential therapeutic targets have been revealed using scRNA-seq. In epilepsy, scRNA-seq has explored the cellular and molecular heterogeneity underlying the condition, uncovering unique glial subpopulations and dysregulation of the immune system. ScRNA-seq has characterised distinct cellular constituents and responses to spinal cord injury in spinal cord diseases, as well as provided molecular signatures of various cell types and identified interactions involved in vascular remodelling. Furthermore, scRNA-seq has shed light on the molecular complexities of cerebrovascular diseases, such as stroke, providing insights into specific genes, cell-specific expression patterns, and potential therapeutic interventions. This review highlights the potential of scRNA-seq in guiding precision medicine approaches, identifying clinical biomarkers, and facilitating therapeutic discovery. However, challenges related to data analysis, standardisation, sample acquisition, scalability, and cost-effectiveness need to be addressed. Despite these challenges, scRNA-seq has the potential to transform clinical practice in neurological and neurosurgical research by providing personalised insights and improving patient outcomes.
  7. Combination of QSAR Modeling and Hybrid-Based Consensus Scoring to Identify Dual-Targeting Inhibitors of PLK1 and p38γ
    Cheng Z, Hwang SS, Bhave M, Rahman T, Chee Wezen X
    J Chem Inf Model, 2023 Nov 13;63(21):6912-6924.
    PMID: 37883148 DOI: 10.1021/acs.jcim.3c01252
    Polo-like kinase 1 (PLK1) and p38γ mitogen-activated protein kinase (p38γ) play important roles in cancer pathogenesis by controlling cell cycle progression and are therefore attractive cancer targets. The design of multitarget inhibitors may offer synergistic inhibition of distinct targets and reduce the risk of drug-drug interactions to improve the balance between therapeutic efficacy and safety. We combined deep-learning-based quantitative structure-activity relationship (QSAR) modeling and hybrid-based consensus scoring to screen for inhibitors with potential activity against the targeted proteins. Using this combination strategy, we identified a potent PLK1 inhibitor (compound 4) that inhibited PLK1 activity and liver cancer cell growth in the nanomolar range. Next, we deployed both our QSAR models for PLK1 and p38γ on the Enamine compound library to identify dual-targeting inhibitors against PLK1 and p38γ. Likewise, the identified hits were subsequently subjected to hybrid-based consensus scoring. Using this method, we identified a promising compound (compound 14) that could inhibit both PLK1 and p38γ activities. At nanomolar concentrations, compound 14 inhibited the growth of human hepatocellular carcinoma and hepatoblastoma cells in vitro. This study demonstrates the combined screening strategy to identify novel potential inhibitors for existing targets.
  8. Identifying Challenges and Potential Solutions for Sustainable Kidney Nutrition Care Delivery in Selected Asian Countries
    Karupaiah T, Mat Daud ZA, Khosla P, Khor BH, Sahathevan S, Kaur D, et al.
    J Ren Nutr, 2023 Nov;33(6S):S73-S79.
    PMID: 37597574 DOI: 10.1053/j.jrn.2023.08.003
    BACKGROUND: Recent surveys highlight gross workforce shortage of dietitians in global kidney health and significant gaps in renal nutrition care, with disparities greater in low/low-middle income countries.

    OBJECTIVE: This paper narrates ground experiences gained through the Palm Tocotrienols in Chronic Hemodialysis (PaTCH) project on kidney nutrition care scenarios and some Asian low-to-middle-income countries namely Bangladesh, India, and Malaysia.

    METHOD: Core PaTCH investigators from 3 universities (USA and Malaysia) were supported by their postgraduate students (n = 17) with capacity skills in kidney nutrition care methodology and processes. This core team, in turn, built capacity for partnering hospitals as countries differed in their ability to deliver dietitian-related activities for dialysis patients.

    RESULTS: We performed a structural component analyses of PaTCH affiliated and nonaffiliated (Myanmar and Indonesia) countries to identify challenges to kidney nutrition care. Deficits in patient-centered care, empowerment processes and moderating factors to nutrition care optimization characterized country comparisons. Underscoring these factors were some countries lacked trained dietitians whilst for others generalist dietitians or nonclinical nutritionists were providing patient care. Resolution of some challenges in low-to-middle-income countries through coalition networking to facilitate interprofessional collaboration and task sharing is described.

    CONCLUSIONS: We perceive interprofessional collaboration is the way forward to fill gaps in essential dietitian services and regional-based institutional coalitions will facilitate culture-sensitive capacity in building skills. For the long-term an advanced renal nutrition course such as the Global Renal Internet Course for Dietitians is vital to facilitate sustainable kidney nutrition care.

  9. The African cancer burden: what is the potential role of modern oncology innovation in reducing the continent's rapidly rising mortality?
    Awuah WA, Ng JC, Mehta A, Nansubuga EP, Abdul-Rahman T, Kundu M, et al.
    Postgrad Med J, 2023 Aug 22;99(1175):941-945.
    PMID: 37280156 DOI: 10.1093/postmj/qgad043
    With increasing prevalence and an expected rise in disease burden, cancer is a cause of concern for African healthcare. The cancer burden in Africa is expected to rise to 2.1 million new cases per year and 1.4 million deaths annually by the year 2040. Even though efforts are being made to improve the standard of oncology service delivery in Africa, the current state of cancer care is not yet on par with the rise in the cancer burden. Cutting-edge technologies and innovations are being developed across the globe to augment the battle against cancer; however, many of them are beyond the reach of African countries. Modern oncology innovations targeted to ward Africa would be promising to address the high cancer mortality rates. The innovations should be cost-effective and widely accessible to tackle the rapidly rising mortality rate on the African continent. Though it may seem promising, a multidisciplinary approach is required to overcome the challenges associated with the development and implementation of modern oncology innovations in Africa.
  10. Fulltext Circadian rhythm in systemic autoimmune conditions: Potential of chrono-immunology in clinical practice: A narrative review
    Awuah WA, Huang H, Kalmanovich J, Mehta A, Mikhailova T, Ng JC, et al.
    Medicine (Baltimore), 2023 Aug 11;102(32):e34614.
    PMID: 37565922 DOI: 10.1097/MD.0000000000034614
    The circadian rhythm (CR) is a fundamental biological process regulated by the Earth's rotation and solar cycles. It plays a critical role in various bodily functions, and its dysregulation can have systemic effects. These effects impact metabolism, redox homeostasis, cell cycle regulation, gut microbiota, cognition, and immune response. Immune mediators, cycle proteins, and hormones exhibit circadian oscillations, supporting optimal immune function and defence against pathogens. Sleep deprivation and disruptions challenge the regulatory mechanisms, making immune responses vulnerable. Altered CR pathways have been implicated in diseases such as diabetes, neurological conditions, and systemic autoimmune diseases (SADs). SADs involve abnormal immune responses to self-antigens, with genetic and environmental factors disrupting self-tolerance and contributing to conditions like Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Inflammatory Myositis. Dysregulated CR may lead to increased production of pro-inflammatory cytokines, contributing to the systemic responses observed in SADs. Sleep disturbances significantly impact the quality of life of patients with SADs; however, they are often overlooked. The relationship between sleep and autoimmune conditions, whether causal or consequential to CR dysregulation, remains unclear. Chrono-immunology investigates the role of CR in immunity, offering potential for targeted therapies in autoimmune conditions. This paper provides an overview of the connections between sleep and autoimmune conditions, highlighting the importance of recognizing sleep disturbances in SADs and the need for further research into the complex relationship between the CR and autoimmune diseases.
  11. Letter: Addressing Neurosurgery Research and Data Access Gaps in War-Inflicted Nations
    Adebusoye FT, Awuah WA, Swaminathan N, Ghosh S, Wellington J, Abdul-Rahman T, et al.
    Neurosurgery, 2023 Aug 01;93(2):e30-e31.
    PMID: 37192472 DOI: 10.1227/neu.0000000000002527
  12. Fulltext The impact of natural disasters on healthcare and surgical services in low- and middle-income countries
    Salam A, Wireko AA, Jiffry R, Ng JC, Patel H, Zahid MJ, et al.
    Ann Med Surg (Lond), 2023 Aug;85(8):3774-3777.
    PMID: 37554857 DOI: 10.1097/MS9.0000000000001041
  13. Fulltext Current state of the use of antibiotic prophylactics in cardiac surgery - correspondence
    Abdul-Rahman T, Omran MO, Ekerin O, Ghosh S, Awuah WA
    Int J Surg, 2023 Aug 01;109(8):2542-2543.
    PMID: 37158146 DOI: 10.1097/JS9.0000000000000445
  14. In Reply: The State of Cerebrovascular Care in Africa
    Awuah WA, Tenkorang PO, Ng JC, Abdul-Rahman T
    Neurosurgery, 2023 Jul 01;93(1):e16.
    PMID: 37097024 DOI: 10.1227/neu.0000000000002515
  15. Fulltext Human soluble CD39 displays substrate inhibition in a substrate-specific manner
    Vadlamani VMK, Gunasinghe KKJ, Chee XW, Rahman T, Harper MT
    Sci Rep, 2023 Jun 02;13(1):8958.
    PMID: 37268726 DOI: 10.1038/s41598-023-36257-3
    CD39 (ectonucleoside triphosphate diphosphohydrolase-1; ENTPD1) metabolizes extracellular ATP and ADP to AMP. AMP is subsequently metabolized by CD79 to adenosine. CD39 activity is therefore a key regulator of purinergic signalling in cancer, thrombosis, and autoimmune diseases. In this study we demonstrate that soluble, recombinant CD39 shows substrate inhibition with ADP or ATP as the substrate. Although CD39 activity initially increased with increasing substrate concentration, at high concentrations of ATP or ADP, CD39 activity was markedly reduced. Although the reaction product, AMP, inhibits CD39 activity, insufficient AMP was generated under our conditions to account for the substrate inhibition seen. In contrast, inhibition was not seen with UDP or UTP as substrates. 2-methylthio-ADP also showed no substrate inhibition, indicating the nucleotide base is an important determinant of substrate inhibition. Molecular dynamics simulations revealed that ADP can undergo conformational rearrangements within the CD39 active site that were not seen with UDP or 2-methylthio-ADP. Appreciating the existence of substrate inhibition of CD39 will help the interpretation of studies of CD39 activity, including investigations into drugs that modulate CD39 activity.
  16. Fulltext Addressing Africa's outrageous neurosurgeons deficit: what could the problem be?
    Wireko AA, Tenkorang PO, Ng JC, David L, Yarlagadda R, Abdul-Rahman T, et al.
    Int J Surg, 2023 Jun 01;109(6):1808-1809.
    PMID: 36927817 DOI: 10.1097/JS9.0000000000000048
  17. NeuroVerse: neurosurgery in the era of Metaverse and other technological breakthroughs
    Kundu M, Ng JC, Awuah WA, Huang H, Yarlagadda R, Mehta A, et al.
    Postgrad Med J, 2023 May 22;99(1170):240-243.
    PMID: 36892407 DOI: 10.1093/postmj/qgad002
    The tremendous evolution in modern technology has led to a paradigm shift in neurosurgery. The latest advancements such as augmented reality, virtual reality, and mobile applications have been incorporated into neurosurgical practice. NeuroVerse, representing the application of the metaverse in neurosurgery, brings enormous potential to neurology and neurosurgery. Implementation of NeuroVerse could potentially elevate neurosurgical and interventional procedures, enhance medical visits and patient care, and reshape neurosurgical training. However, it is also vital to consider the challenges that may be associated with its implementation, such as privacy issues, cybersecurity breaches, ethical concerns, and widening of existing healthcare inequalities. NeuroVerse adds phenomenal dimensions to the neurosurgical environment for patients, doctors, and trainees, and represents an incomparable advancement in the delivery of medicine. Therefore, more research is needed to encourage widespread use of the metaverse in healthcare, particularly focusing on the areas of morality and credibility. Although the metaverse is expected to expand rapidly during and after the COVID-19 pandemic, it remains to be seen whether it represents an emerging technology that will revolutionize our society and healthcare or simply an immature condition of the future.
  18. Fulltext Postoperative mortality in Africa: are there any improvements in the last decade?
    Awuah WA, Ng JC, Nazir A, Tenkorang PO, Yarlagadda R, Kalmanovich J, et al.
    Int J Surg, 2023 May 01;109(5):1080-1082.
    PMID: 36927691 DOI: 10.1097/JS9.0000000000000125
  19. Fulltext Calling for continuous surgical support in Ukraine
    Wireko AA, Ng JC, David L, Abdul-Rahman T, Sikora V, Isik A
    Int J Surg, 2023 Apr 10;110(1):571-3.
    PMID: 37026787 DOI: 10.1097/JS9.0000000000000000
  20. Repurposing FDA-approved drugs as HIV-1 integrase inhibitors: an in silico investigation
    Ha CHX, Lee NK, Rahman T, Hwang SS, Yam WK, Chee XW
    J Biomol Struct Dyn, 2023 Apr;41(6):2146-2159.
    PMID: 35067186 DOI: 10.1080/07391102.2022.2028677
    The Human Immunodeficiency Virus (HIV) infection is a global pandemic that has claimed 33 million lives to-date. One of the most efficacious treatments for naïve or pretreated HIV patients is the HIV integrase strand transfer inhibitors (INSTIs). However, given that HIV treatment is life-long, the emergence of HIV strains resistant to INSTIs is an imminent challenge. In this work, we showed two best regression QSAR models that were constructed using a boosted Random Forest algorithm (r2 = 0.998, q210CV = 0.721, q2external_test = 0.754) and a boosted K* algorithm (r2 = 0.987, q210CV = 0.721, q2external_test = 0.758) to predict the pIC50 values of INSTIs. Subsequently, the regression QSAR models were deployed against the Drugbank database for drug repositioning. The top-ranked compounds were further evaluated for their target engagement activity using molecular docking studies and accelerated Molecular Dynamics simulation. Lastly, their potential as INSTIs were also evaluated from our literature search. Our study offers the first example of a large-scale regression QSAR modelling effort for discovering highly active INSTIs to combat HIV infection.Communicated by Ramaswamy H. Sarma.
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