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  1. Sethi D, Aljunid S, Saperi SB, Zwi AB, Hamid H, Mustafa AN, et al.
    J Trauma, 2002 Sep;53(3):508-16.
    PMID: 12352489
    The effectiveness of trauma services provided by three hospitals operating at different levels of care, district general (DGH), tertiary care, and central tertiary, were compared in Malaysia.
  2. Mustafa AN, Gessner BD, Ismail R, Yusoff AF, Abdullah N, Ishak I, et al.
    Int J Infect Dis, 2003 Sep;7(3):210-4.
    PMID: 14563225
    To determine influenza vaccine effectiveness against clinically defined influenza-like illness among Malaysian pilgrims attending the Haj in Saudi Arabia.
  3. Yousuf R, Mustafa AN, Ho SL, Tang YL, Leong CF
    Asian J Transfus Sci, 2017 3 21;11(1):62-64.
    PMID: 28316444 DOI: 10.4103/0973-6247.200770
    The G antigen of Rh blood group system is present in almost all D-positive or C-positive red cells but absent from red cells lacking D and C antigens. The differentiation of anti-D and anti-C from anti-G is not necessary for routine transfusion; however, during pregnancy, it is important because anti-G can masquerade as anti-D and anti-C with initial antibody testing. The false presence of anti-D will exclude the patient from receiving anti-D immunoglobulin (RhIG) when the patient actually is a candidate for RhIG prophylaxis. Moreover, patients with positive anti-D or anti-G are at risk of developing hemolytic disease of the fetus and newborn and need close monitoring. Thus, proper identification allows the clinicians to manage patients properly. This case report highlights a rare case of anti-G together with anti-D and anti-C in a pregnant woman. This report disseminates knowledge on identification of anti-G and its importance in pregnant women.
  4. Yusoff AF, Mustafa AN, Husaain HM, Hamzah WM, Yusof AM, Harun R, et al.
    BMC Infect Dis, 2013 May 08;13:211.
    PMID: 23656634 DOI: 10.1186/1471-2334-13-211
    BACKGROUND: The aims of the study were to assess the risk factors in relation to cross border activities, exposure to mosquito bite and preventive measures taken.An outbreak of chikungunya virus (CHIKV) infection in Malaysia has been reported in Klang, Selangor (1998) and Bagan Panchor, Perak (2006). In 2009, CHIKV infection re-emerged in some states in Malaysia. It raises the possibilities that re-emergence is part of the epidemics in neighbouring countries or the disease is endemic in Malaysia. For this reason, A community-based case control study was carried out in the state of Kelantan.

    METHODS: Prospective case finding was performed from June to December 2009. Those who presented with signs and symptoms of CHIKV infection were investigated. We designed a case control study to assess the risk factors. Assessment consisted of answering questions, undergoing a medical examination, and being tested for the presence of IgM antibodies to CHIKV. Descriptive epidemiological studies were conducted by reviewing both the national surveillance and laboratory data. Multivariable logistic regression analysis was performed to determine risk factors contributing to the illness. Cases were determined by positive to RT-PCR or serological for antibodies by IgM. CHIKV specificity was confirmed by DNA sequencing.

    RESULTS: There were 129 suspected cases and 176 controls. Among suspected cases, 54.4% were diagnosed to have CHIKV infection. Among the controls, 30.1% were found to be positive to serology for antibodies [IgM, 14.2% and IgG, 15.9%]. For analytic study and based on laboratory case definition, 95 were considered as cases and 123 as controls. Those who were positive to IgG were excluded. CHIKV infection affected all ages and mostly between 50-59 years old. Staying together in the same house with infected patients and working as rubber tappers were at a higher risk of infection. The usage of Mosquito coil insecticide had shown to be a significant protective factor. Most cases were treated as outpatient, only 7.5% needed hospitalization. The CHIKV infection was attributable to central/east African genotype CHIKV.

    CONCLUSIONS: In this study, cross border activity was not a significant risk factor although Thailand and Malaysia shared the same CHIKV genotype during the episode of infections.

  5. Ghazali SM, Seman Z, Cheong KC, Hock LK, Manickam M, Kuay LK, et al.
    BMC Public Health, 2015;15:68.
    PMID: 25636327 DOI: 10.1186/s12889-015-1432-z
    BACKGROUND: To determine the prevalence and sociodemographic correlates of multiple risk factors for cardiovascular disease (CVD) among Malaysian adults.
    METHODS: We analysed data on 1044 men and 1528 women, aged 24-64 years, participants in the Non Communicable Disease Surveillance 2005/2006, a nationally representative, population-based, cross-sectional study. Prevalence of obesity, high blood pressure, dyslipidaemia, hyperglycemia, physical inactivity, smoking, risky drinking, low vegetable and fruit intake were determined and multivariable logistic regression was used to identify sociodemographic factors associated with having ≥3 of these cardiovascular disease risk factors.
    RESULTS: The response rate was 84.6% (2572/3040). Overall, 68.4% (95% CI: 63.2, 73.1) had at least three risk factors. Among men, older age and Indian ethnicity were independently associated with having ≥3 CVD risk factors; while among women, older age, low education, and housewives were more likely to have ≥3 CVD risk factors.
    CONCLUSION: The prevalence of cardiovascular risk factors clustering among Malaysian adults is high, raising concerns that cardiovascular disease incidence will rise steeply in the near future if no immediate preventive measures are taken. The current national health education and promotion programmes pertaining to modifiable risk factors can be further improved by taking into account the sociodemographic variation in CVD risk factors clustering.
    Study name: Malaysia Non-Communicable Disease Surveillance-1 (MyNCDS-1) survey.
  6. Yahya A, Bengtsson C, Larsson P, Too CL, Mustafa AN, Abdullah NA, et al.
    Mod Rheumatol, 2014 Mar;24(2):271-4.
    PMID: 24593203 DOI: 10.3109/14397595.2013.854076
    OBJECTIVES: Silica exposure has been associated with an increased risk of developing rheumatoid arthritis (RA), especially among smokers. In this study, we aimed at examining the association between silica exposure (and its interaction with smoking) and the risk of RA in the Malaysian population.
    METHODS: In total, 149 cases and 213 matched controls, all men, were included between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched on sex, age and residential area. Silica exposure was defined as exposure to stone dust, rock drilling or stone crushing, and smoking status was categorized as ever/never cigarette smoking.
    RESULTS: An increased risk of anti-citrullinated protein antibody (ACPA)-positive RA (OR = 2.4, 95 % CI 1.0-5.6) was observed among those exposed to silica. Ever-smokers exposed to silica had a particularly high risk of developing ACPA-positive RA (OR = 7.5, 95 % CI 2.3-24.2), compared with never-smokers not exposed to silica. No association was found regarding ACPA-negative RA.
    CONCLUSION: Our data demonstrate that exposure to both silica and cigarette smoke comprise risks for developing RA in the Malaysian genetic context. The findings expand a link between environmental lung exposures and ACPA-positive RA to Asian populations.
  7. Abdullah NA, Wan Mahiyuddin WR, Muhammad NA, Ali ZM, Ibrahim L, Ibrahim Tamim NS, et al.
    Asian Pac J Cancer Prev, 2013;14(8):4591-4.
    PMID: 24083707
    Breast cancer is the most common cancer among Malaysian women. Other than hospital-based results, there are no documented population-based survival rates of Malaysian women for breast cancers. This population- based retrospective cohort study was therefore conducted. Data were obtained from Health Informatics Centre, Ministry of Health Malaysia, National Cancer Registry and National Registration Department for the period from 1st Jan 2000 to 31st December 2005. Cases were captured by ICD-10 and linked to death certificates to identify the status. Only complete data were analysed. Survival time was calculated from the estimated date of diagnosis to the date of death or date of loss to follow-up. Observed survival rates were estimated by Kaplan- Meier method using SPSS Statistical Software version 17. A total of 10,230 complete data sets were analysed. The mean age at diagnosis was 50.6 years old. The overall 5-year survival rate was 49% with median survival time of 68.1 months. Indian women had a higher survival rate of 54% compared to Chinese women (49%) and Malays (45%). The overall 5-year survival rate of breast cancer patient among Malaysian women was still low for the cohort of 2000 to 2005 as compared to survival rates in developed nations. Therefore, it is necessary to enhance the strategies for early detection and intervention.
  8. Ghazali SM, Othman Z, Cheong KC, Hock LK, Wan Mahiyuddin WR, Kamaluddin MA, et al.
    Asian Pac J Cancer Prev, 2013;14(2):1141-5.
    PMID: 23621202
    Delay in seeking treatment for breast cancer is a barrier to the early diagnosis and management of the disease, resulting in a poorer prognosis. We here estimated the prevalence of delayed presentation for breast cancer and identified possible influential sociodemographic factors in a cross-sectional study of 250 patients diagnosed with primary breast cancer at the Radiotherapy and Oncology Clinic in Kuala Lumpur Hospital. Data were collected by face-to-face interview using a structured questionnaire and from medical records. We examined associations between delayed presentation (presenting to a physician more than 3 months after self-discovery of a symptom) and sociodemographic characteristics, practice of breast self examination (BSE), history of benign breast disease, family history of breast cancer and type of symptom, symptom disclosure and advice from others to seek treatment using multiple logistic regression. Time from self-discovery of symptom to presentation ranged from tghe same day to 5 years. Prevalence of delayed presentation was 33.1% (95%CI: 27.4, 39.3). A significantly higher proportion of delayers presented with late stages (stage III/IV) (58.3% vs. 26.9%, p<0.001). Divorced or widowed women (OR: 2.23, 95% CI: 1.11, 4.47) had a higher risk of delayed presentation than married women and women who never performed breast self examination were more likely to delay presentation compared to those who regularly performed BSE (OR: 2.74, 95% CI: 1.33, 5.64). Our findings indicate that delayed presentation for breast cancer symptoms among Malaysian women is high and that marital status and breast self examination play major roles in treatment-seeking for breast cancer symptoms.
  9. Yahya A, Bengtsson C, Lai TC, Larsson PT, Mustafa AN, Abdullah NA, et al.
    Mod Rheumatol, 2012 Aug;22(4):524-31.
    PMID: 22006120 DOI: 10.1007/s10165-011-0544-2
    We investigated the association between cigarette smoking and the risk of developing rheumatoid arthritis (RA) in the Malaysian population. A total of 1,056 RA patients and 1,416 matched controls aged 18-70 years within a defined area of Peninsular Malaysia were evaluated in a case-control study between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched for sex, age, and residential area. Cases and controls answered a questionnaire on a broad range of issues, including lifestyle factors and smoking habits wherein current and former smoking was classified as ever-smoking. The presence of anti-citrullinated peptide antibodies (ACPA) was determined for cases and controls. We found that ever-smokers had an increased risk of developing ACPA-positive RA [odds ratio (OR) = 4.1, 95% confidence interval (CI) 1.9-9.2] but not ACPA-negative RA (OR = 0.7, 95% CI 0.3-2.0), compared with never-smokers. A significant dose-response relationship between cumulative dose of smoking and risk of ACPA-positive RA was observed (<20 pack-years OR = 3.3, 95% CI 1.1-9.8; at least 20 pack-years OR = 5.2, 95% CI 1.6-17.6). Hence, smoking is associated with an increased risk of ACPA-positive RA in the Malaysian population, in which the genetic context is similar to several other Asian countries.
  10. Kee CC, Mohd Ghazali S, Lim KH, Subenthiran S, Teh CH, Lim KK, et al.
    Diabetes Metab Syndr, 2015 Apr-Jun;9(2):74-8.
    PMID: 25819369 DOI: 10.1016/j.dsx.2015.02.006
    OBJECTIVES: Many studies have suggested that there is variation in the capabilities of BMI, WC and WHR in predicting cardiometabolic risk and that it might be confounded by gender, ethnicity and age group. The objective of this study is to examine the discriminative abilities of body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR) to predict two or more non-adipose components of the metabolic syndrome (high blood pressure, hypertriglyceridemia, low high density lipoprotein-cholesterol and high fasting plasma glucose) among the adult Malaysian population by gender, age group and ethnicity.
    METHODS: Data from 2572 respondents (1044 men and 1528 women) aged 25-64 years who participated in the Non Communicable Disease Surveillance 2005/2006, a population-based cross sectional study, were analysed. Participants' socio-demographic details, anthropometric indices (BMI, WC and WHR), blood pressure, fasting lipid profile and fasting glucose level were assessed. Receiver operating characteristics curves analysis was used to evaluate the ability of each anthropometric index to discriminate MetS cases from non-MetS cases based on the area under the curve.
    RESULTS: Overall, WC had better discriminative ability than WHR for women but did not perform significantly better than BMI in both sexes, whereas BMI was better than WHR in women only. Waist circumference was a better discriminator of MetS compared to WHR in Malay men and women. Waist circumference and BMI performed better than WHR in Chinese women, men aged 25-34 years and women aged 35-44 years.
    CONCLUSIONS: The discriminative ability of BMI and WC is better than WHR for predicting two or more non-adipose components of MetS. Therefore, either BMI or WC measurements are recommended in screening for metabolic syndrome in routine clinical practice in the effort to combat cardiovascular disease and type II diabetes mellitus.
    Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.
    KEYWORDS: Adult; Body mass index; Metabolic syndrome; Waist circumference; Waist–hip ratio
    Study name: Malaysia Non-Communicable Disease Surveillance-1 (MyNCDS-1) survey
  11. Yahya A, Bengtsson C, Larsson P, Too CL, Mustafa AN, Abdullah NA, et al.
    Mod Rheumatol, 2013 Apr 25.
    PMID: 23615838
    OBJECTIVES: Silica exposure has been associated with an increased risk of developing rheumatoid arthritis (RA), especially among smokers. In this study, we aimed at examining the association between silica exposure (and its interaction with smoking) and the risk of RA in the Malaysian population. METHODS: In total, 149 cases and 213 matched controls, all men, were included between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched on sex, age and residential area. Silica exposure was defined as exposure to stone dust, rock drilling or stone crushing, and smoking status was categorized as ever/never cigarette smoking. RESULTS: An increased risk of anti-citrullinated protein antibody (ACPA)-positive RA (OR = 2.4, 95 % CI 1.0-5.6) was observed among those exposed to silica. Ever-smokers exposed to silica had a particularly high risk of developing ACPA-positive RA (OR = 7.5, 95 % CI 2.3-24.2), compared with never-smokers not exposed to silica. No association was found regarding ACPA-negative RA. CONCLUSION: Our data demonstrate that exposure to both silica and cigarette smoke comprise risks for developing RA in the Malaysian genetic context. The findings expand a link between environmental lung exposures and ACPA-positive RA to Asian populations.
  12. Cheong KC, Ghazali SM, Hock LK, Yusoff AF, Selvarajah S, Haniff J, et al.
    Obes Res Clin Pract, 2014 Mar-Apr;8(2):e154-62.
    PMID: 24743011 DOI: 10.1016/j.orcp.2013.03.004
    INTRODUCTION: Previous studies have proposed the lower waist circumference (WC) cutoffs be used for defining abdominal obesity in Asian populations.
    OBJECTIVE: To determine the optimal cut-offs of waist circumference (WC) in predicting cardiovascular (CV) risk factors in the multi-ethnic Malaysian population.
    METHODS: We analysed data from 32,703 respondents (14,980 men and 17,723 women) aged 18 years and above who participated in the Third National Health and Morbidity Survey in 2006. Gender-specific logistic regression analyses were used to examine associations between WC and three CV risk factors (diabetes mellitus, hypertension, and hypercholesterolemia). The Receiver Operating Characteristic (ROC) curves were used to determine the cut-off values of WC with optimum sensitivity and specificity for detecting these CV risk factors.
    RESULTS: The odds ratio for having diabetes mellitus, hypertension, and hypercholesterolemia, or at least one of these risks, increased significantly as the WC cut-off point increased. Optimal WC cut-off values for predicting the presence of diabetes mellitus, hypertension, hypercholesterolemia and at least one of the three CV risk factors varied from 81.4 to 85.5 cm for men and 79.8 to 80.7 cm for women.
    CONCLUSIONS: Our findings indicate that WC cut-offs of 81 cm for men and 80 cm for women are appropriate for defining abdominal obesity and for recommendation to undergo cardiovascular risk screening and weight management in the Malaysian adult population.
    Study name: National Health and Morbidity Survey (NHMS-2006)
  13. Too CL, Yahya A, Murad S, Dhaliwal JS, Larsson PT, Muhamad NA, et al.
    Arthritis Res Ther, 2012;14(2):R89.
    PMID: 22537824 DOI: 10.1186/ar3813
    INTRODUCTION:Rheumatoid arthritis (RA) is a multifactorial autoimmune disease in which genetic and environmental factors interact in the etiology. In this study, we investigated whether smoking and HLA-DRB1 shared-epitope (SE) alleles interact differently in the development of the two major subgroups of rheumatoid arthritis (RA), anti-citrullinated proteins antibody (ACPA)-positive and ACPA-negative disease, in a multiethnic population of Asian descent.
    METHODS: A case-control study comprising early diagnosed RA cases was carried out in Malaysia between 2005 and 2009. In total, 1,076 cases and 1,612 matched controls participated in the study. High-resolution HLA-DRB1 genotyping was performed for shared-epitope (SE) alleles. All participants answered a questionnaire on a broad range of issues, including smoking habits. The odds ratio (OR) of developing ACPA-positive and ACPA-negative disease was calculated for smoking and the presence of any SE alleles separately. Potential interaction between smoking history (defined as "ever" and "never" smoking) and HLA-DRB1 SE alleles also was calculated.
    RESULTS: In our multiethnic study, both the SE alleles and smoking were associated with an increased risk of developing ACPA-positive RA (OR SE alleles, 4.7; 95% confidence interval (CI), 3.6 to 6.2; OR smoking, 4.1; 95% CI, 1.9 to 9.2). SE-positive smokers had an odds ratio of ACPA-positive RA of 25.6 (95% CI, 10.4 to 63.4), compared with SE-negative never-smokers. The interaction between smoking and SE alleles was significant (attributable proportion due to interaction (AP) was 0.7 (95% CI, 0.5 to 1.0)). The HLA-DRB1*04:05 SE allele, which is common in Asian populations, but not among Caucasians, was associated with an increased risk of ACPA-positive RA, and this allele also showed signs of interaction with smoking (AP, 0.4; 95% CI, -0.1 to 0.9). Neither smoking nor SE alleles nor their combination was associated with an increased risk of ACPA-negative RA.
    CONCLUSIONS: The risk of developing ACPA-positive RA is associated with a strong gene-environment interaction between smoking and HLA-DRB1 SE alleles in a Malaysian multiethnic population of Asian descent. This interaction seems to apply also between smoking and the specific HLA-DRB1*04:05 SE allele, which is common in Asian populations but not in Caucasians.
  14. Cheong KC, Yusoff AF, Ghazali SM, Lim KH, Selvarajah S, Haniff J, et al.
    Public Health Nutr, 2013 Mar;16(3):453-9.
    PMID: 22647482 DOI: 10.1017/S1368980012002911
    OBJECTIVE: To determine the optimal cut-offs of BMI for Malaysian adults.

    DESIGN: Population-based, cross-sectional study. Receiver operating characteristic curves were used to determine the cut-off values of BMI with optimum sensitivity and specificity for the detection of three cardiovascular risk factors: diabetes mellitus, hypertension and hypercholesterolaemia. Gender-specific logistic regression analyses were used to examine the association between BMI and these cardiovascular risk factors.

    SETTING: All fourteen states in Malaysia.

    SUBJECTS: Malaysian adults aged ≥18 years (n 32 703) who participated in the Third National Health and Morbidity Survey in 2006.

    RESULTS: The optimal BMI cut-off value for predicting the presence of diabetes mellitus, hypertension, hypercholesterolaemia or at least one of these cardiovascular risk factors varied from 23.3 to 24.1 kg/m2 for men and from 24.0 to 25.4 kg/m2 for women. In men and women, the odds ratio for having diabetes mellitus, hypertension, hypercholesterolaemia or at least one cardiovascular risk factor increased significantly as BMI cut-off point increased.

    CONCLUSIONS: Our findings indicate that BMI cut-offs of 23.0 kg/m2 in men and 24.0 kg/m2 in women are appropriate for classification of overweight. We suggest that these cut-offs can be used by health professionals to identify individuals for cardiovascular risk screening and weight management programmes.

  15. Zainal Abidin NA, Arith F, Noorasid NS, Sarkawi H, Mustafa AN, Safie NE, et al.
    RSC Adv, 2023 Nov 16;13(48):33797-33819.
    PMID: 38020037 DOI: 10.1039/d3ra04823c
    The conventional electron transport layer (ETL) TiO2 has been widely used in perovskite solar cells (PSCs), which have produced exceptional power conversion efficiencies (PCE), allowing the technology to be highly regarded and propitious. Nevertheless, the recent high demand for energy harvesters in wearable electronics, aerospace, and building integration has led to the need for flexible solar cells. However, the conventional TiO2 ETL layer is less preferred, where a crystallization process at a temperature as high as 450 °C is required, which degrades the plastic substrate. Zinc oxide nanorods (ZnO NRs) as a simple and low-cost fabrication material may fulfil the need as an ETL, but they still suffer from low PCE due to atomic defect vacancy. To delve into the issue, several dopants have been reviewed as an additive to passivate or substitute the Zn2+ vacancies, thus enhancing the charge transport mechanism. This work thereby unravels and provides a clear insight into dopant engineering in ZnO NRs ETL for PSC.
  16. Hock LK, Ghazali SM, Cheong KC, Kuay LK, Li LH, Huey TC, et al.
    Asian Pac J Cancer Prev, 2014;15(10):4359-66.
    PMID: 24935397
    Intention to smoke is a valid and reliable factor for predicting future smoking habits among adolescents. This factor, however, has received inadequate attention in Malaysia. The present paper elaborates the prevalence and factors associated with intent to initiate or to cease smoking, among adolescent nonsmokers and smokers in Kota Tinggi, Johor, Malaysia. A total of 2,300 secondary school students aged 13-16 years were selected through a two-stage stratified sampling method. A set of standardized questionnaires was used to assess the smoking behavior among adolescents and the inter-personal and intra-personal factors associated with smoking intention (intention to initiate smoking or to cease smoking). Multivariable logistic regression was used to identify factors related to smoking intention. The prevalence of intention to smoke in the future or to cease smoking among non- smoking adolescents and current smokers were 10.7% and 61.7% respectively. Having friends who smoke, social influence, and poor knowledge about the ill effects on health due to smoking showed significant relationships with intention to smoke in the future among non-smokers. Conversely, perceived lower prevalence of smoking among peers, weak contributory social influence, and greater awareness of the ill effects of smoking are factors associated with the intention to cease smoking sometime in the future. The study found that prevalence of intention to initiate smoking is low among non-smokers while the majority of current smokers intended to cease smoking in the future. Existing anti-smoking programmes that integrate the factors that have been identified in the current study should be put in motion to reduce the prevalence of intention to initiate smoking and increase the intention to cease smoking among adolescents.
  17. Parashar UD, Sunn LM, Ong F, Mounts AW, Arif MT, Ksiazek TG, et al.
    J Infect Dis, 2000 May;181(5):1755-9.
    PMID: 10823779
    An outbreak of encephalitis affecting 265 patients (105 fatally) occurred during 1998-1999 in Malaysia and was linked to a new paramyxovirus, Nipah, that infected pigs, humans, dogs, and cats. Most patients were pig farmers. Clinically undetected Nipah infection was noted in 10 (6%) of 166 community-farm controls (persons from farms without reported encephalitis patients) and 20 (11%) of 178 case-farm controls (persons from farms with encephalitis patients). Case patients (persons with Nipah infection) were more likely than community-farm controls to report increased numbers of sick/dying pigs on the farm (59% vs. 24%, P=.001) and were more likely than case-farm controls to perform activities requiring direct contact with pigs (86% vs. 50%, P=.005). Only 8% of case patients reported no contact with pigs. The outbreak stopped after pigs in the affected areas were slaughtered and buried. Direct, close contact with pigs was the primary source of human Nipah infection, but other sources, such as infected dogs and cats, cannot be excluded.
  18. Yin T, Xu L, Gil B, Merali N, Sokolikova MS, Gaboriau DCA, et al.
    ACS Nano, 2023 Aug 08;17(15):14619-14631.
    PMID: 37470391 DOI: 10.1021/acsnano.3c01812
    Biosensors based on graphene field effect transistors (GFETs) have the potential to enable the development of point-of-care diagnostic tools for early stage disease detection. However, issues with reproducibility and manufacturing yields of graphene sensors, but also with Debye screening and unwanted detection of nonspecific species, have prevented the wider clinical use of graphene technology. Here, we demonstrate that our wafer-scalable GFETs array platform enables meaningful clinical results. As a case study of high clinical relevance, we demonstrate an accurate and robust portable GFET array biosensor platform for the detection of pancreatic ductal adenocarcinoma (PDAC) in patients' plasma through specific exosomes (GPC-1 expression) within 45 min. In order to facilitate reproducible detection in blood plasma, we optimized the analytical performance of GFET biosensors via the application of an internal control channel and the development of an optimized test protocol. Based on samples from 18 PDAC patients and 8 healthy controls, the GFET biosensor arrays could accurately discriminate between the two groups while being able to detect early cancer stages including stages 1 and 2. Furthermore, we confirmed the higher expression of GPC-1 and found that the concentration in PDAC plasma was on average more than 1 order of magnitude higher than in healthy samples. We found that these characteristics of GPC-1 cancerous exosomes are responsible for an increase in the number of target exosomes on the surface of graphene, leading to an improved signal response of the GFET biosensors. This GFET biosensor platform holds great promise for the development of an accurate tool for the rapid diagnosis of pancreatic cancer.
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