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The unmet need of organ transplantation in Africa

Awuah WA, Ng JC, Bulut HI, Nazir A, Tenkorang PO, Yarlagadda R, et al.

Int J Surg, 2023 Mar 01;109(3):519-520.
PMID: 36927835 DOI: 10.1097/JS9.0000000000000025
Fulltext The state of African surgical research capacity: highlighting the current efforts, challenges, and recommendations - Editorial

Wireko AA, Ohenewaa Tenkorang P, Tope Adebusoye F, Mehta A, Cheng Ng J, Yaa Asieduwaa O, et al.

Int J Surg, 2023 Feb 01;109(2):91-93.
PMID: 36799813 DOI: 10.1097/JS9.0000000000000216
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.
Fulltext The importance of pharmacists in modern day surgery - editorial

Wireko AA, Ohenewaa Tenkorang P, Tope Adebusoye F, Yaa Asieduwaa O, Mehta A, Fosuah Debrah A, et al.

Int J Surg, 2023 Feb 01;109(2):88-90.
PMID: 36799812 DOI: 10.1097/JS9.0000000000000146
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
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.
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.
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
Fulltext Observational study of the status of coronary risk biomarkers among Negritos with metabolic syndrome in the east coast of Malaysia

Mokhsin A, Mokhtar SS, Mohd Ismail A, M Nor F, Shaari SA, Nawawi H, et al.

BMJ Open, 2018 12 04;8(12):e021580.
PMID: 30518581 DOI: 10.1136/bmjopen-2018-021580

OBJECTIVES: To determine the prevalence of metabolic syndrome (MS), ascertain the status of coronary risk biomarkers and establish the independent predictors of these biomarkers among the Negritos.
SETTINGS: Health screening programme conducted in three inland settlements in the east coast of Malaysia and Peninsular Malaysia.
SUBJECTS: 150 Negritos who were still living in three inland settlements in the east coast of Malaysia and 1227 Malays in Peninsular Malaysia. These subjects were then categorised into MS and non-MS groups based on the International Diabetes Federation (IDF) consensus worldwide definition of MS and were recruited between 2010 and 2015. The subjects were randomly selected and on a voluntary basis.
PRIMARY AND SECONDARY OUTCOME MEASURES: This study was a cross-sectional study. Serum samples were collected for analysis of inflammatory (hsCRP), endothelial activation (sICAM-1) and prothrombogenesis [lp(a)] biomarkers.
RESULTS: MS was significantly higher among the Malays compared with Negritos (27.7%vs12.0%). Among the Malays, MS subjects had higher hsCRP (p=0.01) and sICAM-1 (p<0.05) than their non-MS counterpart. There were no significant differences in all the biomarkers between MS and the non-MS Negritos. However, when compared between ethnicity, all biomarkers were higher in Negritos compared with Malays (p<0.001). Binary logistic regression analysis affirmed that Negritos were an independent predictor for Lp(a) concentration (p<0.001).
CONCLUSIONS: This study suggests that there may possibly be a genetic influence other than lifestyle, which could explain the lack of difference in biomarkers concentration between MS and non-MS Negritos and for Negritos predicting Lp(a).
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.
Fulltext Natural selection and local adaptation of blood pressure regulation and their perspectives on precision medicine in hypertension

Hoh BP, Abdul Rahman T, Yusoff K

Hereditas, 2019;156:1.
PMID: 30636949 DOI: 10.1186/s41065-019-0080-1

Prevalence of hypertension (HTN) varies substantially across different populations. HTN is not only common - affecting at least one third of the world's adult population - but is also the most important driver for cardiovascular diseases. Yet up to a third of hypertensive patients are resistant to therapy, contributed by secondary hypertension but more commonly the hitherto inability to precisely predict response to specific antihypertensive agents. Population and individual genomics information could be useful in guiding the selection and predicting the response to treatment - an approach known as precision medicine. However this cannot be achieved without the knowledge of genetic variations that influence blood pressure (BP). A number of evolutionary factors including population demographics and forces of natural selection may be involved. This article explores some ideas on how natural selection influences BP regulation in ethnically and geographically diverse populations that could lead to them being susceptible to HTN. We explore how such evolutionary factors could impact the implementation of precision medicine in HTN. Finally, in order to ensure the success of precision medicine in HTN, we call for more initiatives to understand the genetic architecture within and between diverse populations with ancestry from different parts of the world, and to precisely classify the intermediate phenotypes of HTN.
Multilevel Pharmacological Effects of Antipsychotics in Potential Glioblastoma Treatment

Awuah WA, Kalmanovich J, Mehta A, Huang H, Abdul-Rahman T, Cheng Ng J, et al.

Curr Top Med Chem, 2023;23(5):389-402.
PMID: 36593538 DOI: 10.2174/1568026623666230102095836

Glioblastoma Multiforme (GBM) is a debilitating type of brain cancer with a high mortality rate. Despite current treatment options such as surgery, radiotherapy, and the use of temozolomide and bevacizumab, it is considered incurable. Various methods, such as drug repositioning, have been used to increase the number of available treatments. Drug repositioning is the use of FDA-approved drugs to treat other diseases. This is possible because the drugs used for this purpose have polypharmacological effects. This means that these medications can bind to multiple targets, resulting in multiple mechanisms of action. Antipsychotics are one type of drug used to treat GBM. Antipsychotics are a broad class of drugs that can be further subdivided into typical and atypical classes. Typical antipsychotics include chlorpromazine, trifluoperazine, and pimozide. This class of antipsychotics was developed early on and primarily works on dopamine D2 receptors, though it can also work on others. Olanzapine and Quetiapine are examples of atypical antipsychotics, a category that was created later. These medications have a high affinity for serotonin receptors such as 5- HT2, but they can also act on dopamine and H1 receptors. Antipsychotic medications, in the case of GBM, also have other effects that can affect multiple pathways due to their polypharmacological effects. These include NF-B suppression, cyclin deregulation, and -catenin phosphorylation, among others. This review will delve deeper into the polypharmacological, the multiple effects of antipsychotics in the treatment of GBM, and an outlook for the field's future progression.
Fulltext Metabolomics and partial least square discriminant analysis to predict history of myocardial infarction of self-claimed healthy subjects: validity and feasibility for clinical practice

Mohamad N, Ismet RI, Rofiee M, Bannur Z, Hennessy T, Selvaraj M, et al.

J Clin Bioinforma, 2015;5:3.
PMID: 25806102 DOI: 10.1186/s13336-015-0018-4

The dynamics of metabolomics in establishing a prediction model using partial least square discriminant analysis have enabled better disease diagnosis; with emphasis on early detection of diseases. We attempted to translate the metabolomics model to predict the health status of the Orang Asli community whom we have little information. The metabolite expressions of the healthy vs. diseased patients (cardiovascular) were compared. A metabotype model was developed and validated using partial least square discriminant analysis (PLSDA). Cardiovascular risks of the Orang Asli were predicted and confirmed by biochemistry profiles conducted concurrently.
Letter: The State of Cerebrovascular Care in Africa

Tenkorang PO, Awuah WA, Ng JC, Kalmanovich J, Nazir A, Yarlagadda R, et al.

Neurosurgery, 2023 Mar 01;92(3):e72-e73.
PMID: 36700753 DOI: 10.1227/neu.0000000000002330
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
Inference of the Genetic Polymorphisms of CYP2D6 in Six Subtribes of the Malaysian Orang Asli from Whole-Genome Sequencing Data

Yu CY, Ang GY, Subramaniam V, Johari James R, Ahmad A, Abdul Rahman T, et al.

Genet Test Mol Biomarkers, 2017 Jul;21(7):409-415.
PMID: 28525288 DOI: 10.1089/gtmb.2016.0235

AIMS: CYP2D6 is one of the major enzymes in the cytochrome P450 monooxygenase system. It metabolizes ∼25% of prescribed drugs and hence, the genetic diversity of a CYP2D6 gene has continued to be of great interest to the medical and pharmaceutical industries. This study was designed to perform a systematic analysis of the CYP2D6 gene in six subtribes of the Malaysian Orang Asli.
METHODS: Genomic DNAs were extracted from the blood samples followed by whole-genome sequencing. The reads were aligned to the reference human genome hg19 and variants in the CYP2D6 gene were analyzed. CYP2D6*5 and duplication of CYP2D6 were analyzed using previously established methods.
RESULTS: A total of 72 single nucleotide polymorphisms were identified. CYP2D6*1, *2, *4, *5, *10,*41, and duplication of the gene were found in the Orang Asli, whereby CYP2D6*2 and *41 alleles are reported for the first time in the Malaysian population.
CONCLUSION: The findings in this study provide insights into the genetic polymorphisms of CYP2D6 in the Orang Asli of Peninsular Malaysia.
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
Hepatitis B virus infection: Epidemiology and seroprevalence rate amongst Negrito tribe in Malaysia

Sahlan N, Fadzilah MN, Muslim A, Shaari SA, Abdul Rahman T, Hoh BP

Med J Malaysia, 2019 08;74(4):320-325.
PMID: 31424040

INTRODUCTION: Prevalence of Hepatitis B virus (HBV) infection among the non-indigenous people in Malaysia has been well established and range between 3% and 5%. However, data from the indigenous (Orang Asli) people is still lacking. The Negrito population is the most remotely located Orang Asli tribe with limited access to health care facilities. This study was undertaken to determine the epidemiology and seroprevalence of HBV infection among the Negrito.
METHODS: Surveys were conducted in five Negrito settlements in Kelantan and Perak states in Malaysia. A total of 150 participants were recruited. Clinical history was taken and physical examination was performed. Five millilitres of whole blood were collected and tested for hepatitis B surface antigen (HBsAg) using electrochemiluminescence immunoassay.
RESULTS: Participants were mainly from the Bateq (49.3%) and Mendriq (29.4%) sub-tribes. Overall, 13 subjects (8.7 %); nine males and four females were HBsAg positive. Nine of the HBsAg positive subjects were ≥35 years old. All of them had history of home deliver without evidence of antenatal record. Six (46%) of the HBsAg positive subjects had tattoo and body piercing in the past.
CONCLUSION: The prevalence of HBV infection rate amongst the Negrito tribe is almost three-fold compared to the national rates. The reason for this finding remains unclear. Tattooing, body piercing and vertical transmission could be the main possible routes of transmission of HBV among the Negrito population in Malaysia.
Genomic structure of the native inhabitants of Peninsular Malaysia and North Borneo suggests complex human population history in Southeast Asia

Yew CW, Lu D, Deng L, Wong LP, Ong RT, Lu Y, et al.

Hum Genet, 2018 Feb;137(2):161-173.
PMID: 29383489 DOI: 10.1007/s00439-018-1869-0

Southeast Asia (SEA) is enriched with a complex history of peopling. Malaysia, which is located at the crossroads of SEA, has been recognized as one of the hubs for early human migration. To unravel the genomic complexity of the native inhabitants of Malaysia, we sequenced 12 samples from 3 indigenous populations from Peninsular Malaysia and 4 native populations from North Borneo to a high coverage of 28-37×. We showed that the Negritos from Peninsular Malaysia shared a common ancestor with the East Asians, but exhibited some level of gene flow from South Asia, while the North Borneo populations exhibited closer genetic affinity towards East Asians than the Malays. The analysis of time of divergence suggested that ancestors of Negrito were the earliest settlers in the Malay Peninsula, whom first separated from the Papuans ~ 50-33 thousand years ago (kya), followed by East Asian (~ 40-15 kya), while the divergence time frame between North Borneo and East Asia populations predates the Austronesian expansion period implies a possible pre-Neolithic colonization. Substantial Neanderthal ancestry was confirmed in our genomes, as was observed in other East Asians. However, no significant difference was observed, in terms of the proportion of Denisovan gene flow into these native inhabitants from Malaysia. Judging from the similar amount of introgression in the Southeast Asians and East Asians, our findings suggest that the Denisovan gene flow may have occurred before the divergence of these populations and that the shared similarities are likely an ancestral component.
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.

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