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Oral cancer secretome: identification of cancer-associated proteins

Chang HY, Hor SY, Lim KP, Zain RB, Cheong SC, Rahman MA, et al.

Electrophoresis, 2013 Aug;34(15):2199-208.
PMID: 23712713 DOI: 10.1002/elps.201300126

This study aims to identify cancer-associated proteins in the secretome of oral cancer cell lines. We have successfully established four primary cell cultures of normal cells with a limited lifespan without human telomerase reverse transcriptase (hTERT) immortalization. The secretome of these primary cell cultures were compared with that of oral cancer cell lines using 2DE. Thirty five protein spots were found to have changed in abundance. Unambiguous identification of these proteins was achieved by MALDI TOF/TOF. In silico analysis predicted that 24 of these proteins were secreted via classical or nonclassical mechanisms. The mRNA expression of six genes was found to correlate with the corresponding protein abundance. Ingenuity Pathway Analysis (IPA) core analysis revealed that the identified proteins were relevant in, and related to, cancer development with likely involvements in tumor growth, metastasis, hyperproliferation, tumorigenesis, neoplasia, hyperplasia, and cell transformation. In conclusion, we have demonstrated that a comparative study of the secretome of cancer versus normal cell lines can be used to identify cancer-associated proteins.
Fulltext Changes in COVID-19 risk perceptions: methods of an internet survey conducted in six countries

Zhang F, Shih SF, Harapan H, Rajamoorthy Y, Chang HY, Singh A, et al.

BMC Res Notes, 2021 Nov 25;14(1):428.
PMID: 34823587 DOI: 10.1186/s13104-021-05846-8

OBJECTIVES: This study assessed changes in behaviors/attitudes related to the COVID-19. With the understanding that behaviors and vaccine decision-making could contribute to global spread of infectious diseases, this study collected several waves of internet-based surveys from individuals in the United States, mainland China, Taiwan, Malaysia, Indonesia, and India. The aims of this study were to (1) characterize the relationship between the epidemiology of disease and changes over time in risk perceptions, knowledge, and attitudes towards hygienic behaviors; (2) examine if risk perceptions affect acceptance of less-than-ideal vaccines; and (3) contrast adherence to public health recommendations across countries which have had different governmental responses to the outbreak.
DATA DESCRIPTION: We conducted cross-sectional online surveys in six countries from March 2020 to April 2021. By the end of June 2021, there will be six waves of surveys for the United States and China, and four waves for the rest of countries. There are common sets of questions for all countries, however, some questions were adapted to reflect local situations and some questions were designed intentionally for specific countries to capture different COVID-19 mitigation actions. Participants were asked about their adherence towards countermeasures, risk perceptions, and acceptance of a hypothetical vaccine for COVID-19.
Fulltext Parental vaccine hesitancy and acceptance of a COVID-19 vaccine: An internet-based survey in the US and five Asian countries

Joachim G, Shih SF, Singh A, Rajamoorthy Y, Harapan H, Chang HY, et al.

PLOS Glob Public Health, 2024;4(2):e0002961.
PMID: 38416781 DOI: 10.1371/journal.pgph.0002961

COVID-19 vaccination rates for children globally are relatively low. This study aimed to investigate parental vaccine hesitancy and parents' acceptance of a COVID-19 for their children for their children in the United States, China, Taiwan, India, Indonesia, and Malaysia.We analyzed data from an opt-in, internet-based cross-sectional study (n = 23,940). Parents were asked about their acceptance of a COVID-19 vaccine for their children, and if they would accept the vaccine with different risk and effectiveness profiles for themselves. Poisson regression was used to generate prevalence ratios (PR) of the relationship between vaccine acceptance for a child and vaccine profile, by country and waves and overall. Between August 2020 and June 2021, COVID-19 vaccine acceptance for children decreased in the United States (89% to 72%) and Taiwan (79% to 71%), increased in India (91% to 96%) and Malaysia (81% to 91%), and was stable in Indonesia (86%) and China (at 87%-90%). Vaccine risk and effectiveness profiles did not consistently affect parent's acceptance of a COVID-19 vaccine for their children. Instead, being not hesitant was a large driver of vaccine acceptance (PR: 1.24, 95% CI: 1.14, 1.36). Adolescent COVID-19 vaccination have already been established in many high and middle-income countries, but our study suggests that there is a movement of vaccine hesitancy which could impede the success of future pediatric and adolescent COVID-19 vaccination programs.
Fulltext A study of COVID-19 vaccination in the US and Asia: The role of media, personal experiences, and risk perceptions

Akel KB, Noppert GA, Rajamoorthy Y, Lu Y, Singh A, Harapan H, et al.

PLOS Glob Public Health, 2022;2(7):e0000734.
PMID: 36962371 DOI: 10.1371/journal.pgph.0000734

The COVID-19 pandemic presents an opportunity to assess the relationship between personal experiences and vaccine decision-making. The aim of this study was to examine the associations between experiences with COVID-19 and COVID-19 vaccination status. We administered 28 repeated cross-sectional, online surveys between June 2020 and June 2021 in the US and Asia. The main exposure was media showing COVID-19 cases, and we distinguished those with no such experience, those seeing a not severe case of disease, and those seeing a severe case of disease. Logistic regression models estimated the association between experience and acceptance of a hypothetical COVID-19 vaccine (pre-rollout) or actual vaccination (post-rollout). We explored perceived susceptibility as a potential mediator. Intent to vaccinate was lowest in the US and Taiwan, and highest in India, Indonesia, and China. Across all countries, seeing a severe case of COVID-19 in the media was associated with 1.72 times higher odds of vaccination intent in 2020 (95% CI: 1.46, 2.02) and 2.13 times higher odds of vaccination in 2021 (95% CI: 1.70, 2.67), compared to those not seeing a case or a less severe case. Perceived susceptibility was estimated to mediate 25% of the relationship with hypothetical vaccination (95% CI: 18%, 31%, P<0.0001), and 16% of the relationship with actual vaccination 16% (95% CI: 12%, 19%, P<0.0001). Seriousness of experiences could relate to intention to vaccinate against COVID-19. Media exposures are a modifiable experience, and this study highlights how this experience can relate to risk perceptions and eventual vaccination, across a variety of countries where the course of the pandemic differed.
Surveillance of pesticide poisoning in an East and a West Malaysian hospital: characteristics of pesticide poisoning and the early impact of a national Paraquat ban

Chan LF, Chin SJ, Loo TH, Panirselvam RR, Chang SS, Chang HY, et al.

BMC Psychiatry, 2023 Jun 28;23(1):472.
PMID: 37380953 DOI: 10.1186/s12888-023-04974-8

BACKGROUND: Previous studies have shown that pesticide bans were associated with reduced fatal pesticide self-poisoning cases in high, and low-and-middle-income countries. We aimed to investigate the characteristics of pesticide poisoning patients admitted to two Malaysian hospitals and the early impact of the national paraquat ban implemented on 1st January 2020 in a culturally heterogenous South-East-Asian upper-middle-income setting.
METHODS: Data were collected from an East (Bintulu) and a West (Ipoh) Malaysian hospital medical records in 2015-2021 and 2018-2021, respectively. Logistic regression analyses were conducted to investigate the association of aspects such as socio-demographic and clinical characteristics, paraquat ban with the types of pesticides involved (paraquat versus non-paraquat versus unknown) ,and the outcomes (fatal versus non-fatal).
RESULTS: From the study sample of 212 pesticide poisoning patients aged 15 years or above, the majority were self-poisoning cases (75.5%) with a disproportionate over-representation of Indian ethnic minority (44.8%). Most pesticide poisoning cases had socio-environmental stressors (62.30%). The commonest stressors were domestic interpersonal conflicts (61.36%). 42.15% of pesticide poisoning survivors had a psychiatric diagnosis. Paraquat poisoning accounted for 31.6% of all patients and 66.7% of fatalities. Case fatality was positively associated with male gender, current suicidal intent, and paraquat poisoning. After the paraquat ban, the proportion of pesticide poisoning cases using paraquat decreased from 35.8 to 24.0%, and the overall case-fatality dropped slightly from 21.2 to 17.3%.
CONCLUSIONS: Socio-environmental stressors in specific domestic interpersonal conflicts, seemed more prominent in pesticide poisoning compared to psychiatric diagnosis. Paraquat accounted for the majority of pesticide-associated deaths occurring in hospitals in the study areas. There was preliminary evidence that the 2020 paraquat ban led to a fall in case fatality from pesticide poisoning.
Fulltext Asia-Pacific Real-World Evolocumab Use, LDL-C Reduction, Physician Goals, and Patient Perceptions: HALES Observational Study

Tse HF, Chang HY, Colquhoun D, Kim JS, Poh KK, Kostner K, et al.

Cardiol Ther, 2024 Dec;13(4):737-760.
PMID: 39455535 DOI: 10.1007/s40119-024-00384-3

INTRODUCTION: Real-world data are needed to understand the effectiveness of new therapeutic options for low-density lipoprotein cholesterol (LDL-C) reduction in Asia-Pacific clinical practice. Description of evolocumab use among adults with establisHed Atherosclerotic cardiovascuLar diseasE or hypercholesterolemia in ASia-Pacific region (HALES) was performed to better understand characteristics of and clinical decision-making for adults with established atherosclerotic cardiovascular disease/hypercholesterolemia after local evolocumab approval.
METHODS: The HALES observational study, conducted at 33 sites (Hong Kong, Thailand, South Korea, Singapore, Taiwan, and Australia) comprised (1) chart review of patients who received evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i), and (2) physician/patient survey and one-time data collection of patients with high cardiovascular risk initiating evolocumab or initiating/continuing non-PCSK9i lipid-lowering therapy. Patients could only enroll in (1) or (2).
RESULTS: Chart review included 724 very high-risk patients initiating evolocumab from regulatory approval to 2021. From median baseline LDL-C of 3.2 mmol/L (123.7 mg/dL), patients had a median percent change in LDL-C of - 60.8% at 1-6 months. Goal achievement increased from 7.9% to 69.8% for
Downregulation of CRNN gene and genomic instability at 1q21.3 in oral squamous cell carcinoma

Salahshourifar I, Vincent-Chong VK, Chang HY, Ser HL, Ramanathan A, Kallarakkal TG, et al.

Clin Oral Investig, 2015 Dec;19(9):2273-83.
PMID: 25846277 DOI: 10.1007/s00784-015-1467-7

OBJECTIVES: This study includes the direct sequencing of cornulin (CRNN) gene to elucidate the possible mechanism of CRNN downregulation and explore the genetic imbalances at 1q21.3 across oral squamous cell carcinoma (OSCC) samples.
MATERIALS AND METHODS: In mutation screening of CRNN gene, gDNA from OSCC tissues were extracted, amplified, and followed by direct sequencing. OSCC samples were also subjected to fragment analysis on CRNN gene to investigate its microsatellite instability (MSI) and loss of heterozygosity (LOH). Immunohistochemistry was performed to validate CRNN downregulation in OSCC samples.
RESULTS: No pathogenic mutation was found in CRNN gene, while high frequency of allelic imbalances was found at 1q21.3 region. MSI was found more frequent (25.3 %) than LOH (9.3 %). Approximately 22.6 % of cases had high MSI which reflects higher probability of inactivation of DNA mismatch repair genes. MSI showed significant association with no betel quid chewing (p = 0.003) and tongue subsite (p = 0.026). LOH was associated with ethnicity (p = 0.008) and advanced staging (p = 0.039). The LOH at 1q21.3 was identified to be as an independent prognostic marker in OSCC (HRR = 7.15 (95 % CI, 1.41-36.25), p = 0.018). Downregulation of CRNN was found among MSI-positive OSCCs and was associated with poor prognosis (p = 0.044).
CONCLUSION: This study showed a significant correlation between LOH/MSI at 1q21.3 with clinical outcomes and that downregulation of CRNN gene could be considered as a prognostic marker of OSCC.
CLINICAL RELEVANCE: Insights of the downregulation mode of CRNN gene lays the basis of drug development on this gene as well as revealing its prognostic value.