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  1. Adikusuma W, Zakaria ZA, Irham LM, Nopitasari BL, Pradiningsih A, Firdayani F, et al.
    Sci Rep, 2023 Jun 20;13(1):10032.
    PMID: 37340026 DOI: 10.1038/s41598-023-37120-1
    Diabetic foot ulcers (DFUs) are a common complication of diabetes and can lead to severe disability and even amputation. Despite advances in treatment, there is currently no cure for DFUs and available drugs for treatment are limited. This study aimed to identify new candidate drugs and repurpose existing drugs to treat DFUs based on transcriptomics analysis. A total of 31 differentially expressed genes (DEGs) were identified and used to prioritize the biological risk genes for DFUs. Further investigation using the database DGIdb revealed 12 druggable target genes among 50 biological DFU risk genes, corresponding to 31 drugs. Interestingly, we highlighted that two drugs (urokinase and lidocaine) are under clinical investigation for DFU and 29 drugs are potential candidates to be repurposed for DFU therapy. The top 5 potential biomarkers for DFU from our findings are IL6ST, CXCL9, IL1R1, CXCR2, and IL10. This study highlights IL1R1 as a highly promising biomarker for DFU due to its high systemic score in functional annotations, that can be targeted with an existing drug, Anakinra. Our study proposed that the integration of transcriptomic and bioinformatic-based approaches has the potential to drive drug repurposing for DFUs. Further research will further examine the mechanisms by which targeting IL1R1 can be used to treat DFU.
    Matched MeSH terms: Humans
  2. Rengarajoo J, Harun RH, Royan SJ, Kohir S, Mamat MR
    Ann R Coll Surg Engl, 2022 Jul;104(7):556.
    PMID: 35174718 DOI: 10.1308/rcsann.2021.0299
    Matched MeSH terms: Humans
  3. Yap LS, Lee WL, Ting ASY
    Prep Biochem Biotechnol, 2023;53(6):653-671.
    PMID: 36137173 DOI: 10.1080/10826068.2022.2122064
    L-asparaginase is an enzyme commonly used to treat acute lymphoblastic leukemia. Commercialized bacterial L-asparaginase has been reported to cause several life-threatening complications during treatment, hence the need to seek alternative sources of L-asparaginase. In this study, the novelty of upstream and downstream bioprocessing of L-asparaginase from a fungal endophyte, Colletotrichum gloeosporioides, and the cytotoxicity evaluation was demonstrated. Six variables (carbon source and concentration, nitrogen source and concentration, incubation period, temperature, pH and agitation rate) known to influence L-asparaginase production were studied using One-Factor-At-A-Time (OFAT) approach, with four significant variables further optimized using Response Surface Methodology (RSM). The crude extract produced using optimized condition was purified, characterized and examined for its anticancer effect. Purification of fungal L-asparaginase was performed via ultrafiltration and size exclusion chromatography, which are less common techniques. The protein profile and monomeric weight of L-asparaginase were determined using SDS-PAGE and Western blot. Cytotoxicity of purified L-asparaginase on leukemic Jurkat E6 and oral carcinoma cells were studied using MTS assay for 24 h and 48 h. OFAT results from optimization showed that glucose and L-asparagine concentrations, incubation period and temperature, were significant factors affecting L-asparaginase production by C. gloeosporioides. RSM analysis further evidence the significant interaction between glucose and L-asparagine concentrations in inducing L-asparaginase production. Purified L-asparaginase was profiled with specific activity of 255.02 IU/mg protein, purification fold of 6.12, and 34.63% of enzyme recovery. SDS and Western blot revealed that the purified L-asparaginase might be a tetramer with monomeric units of 25 kDa. Purified L-asparaginase was discovered to be more efficient against Jurkat leukemic cells than against H103 oral carcinoma cells, as lower IC50 value was observed for Jurkat cell lines (46 .36 ± 1.52 µg/mL for Jurkat and 125.56 ± 7.28 µg/mL for H103). In short, purified L-asparaginase derived from endophytic C. gloeosporioides showed high purity and significant anticancer effect toward cancer cells. This study therefore demonstrated the potential of fungal L-asparaginase as alternative chemotherapy drug in the future.
    Matched MeSH terms: Humans
  4. Im SA, Gennari A, Park YH, Kim JH, Jiang ZF, Gupta S, et al.
    ESMO Open, 2023 Jun;8(3):101541.
    PMID: 37178669 DOI: 10.1016/j.esmoop.2023.101541
    The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer (MBC) was published in 2021. A special, hybrid guidelines meeting was convened by ESMO and the Korean Society of Medical Oncology (KSMO) in collaboration with nine other Asian national oncology societies in May 2022 in order to adapt the ESMO 2021 guidelines to take into account the differences associated with the treatment of MBC in Asia. These guidelines represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with MBC representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). The voting was based on the best available scientific evidence and was independent of drug access or practice restrictions in the different Asian countries. The latter were discussed when appropriate. The aim of these guidelines is to provide guidance for the harmonisation of the management of patients with MBC across the different regions of Asia, drawing from data provided by global and Asian trials whilst at the same time integrating the differences in genetics, demographics and scientific evidence, together with restricted access to certain therapeutic strategies.
    Matched MeSH terms: Humans
  5. Bernhardt J, Churilov L, Dewey H, Donnan G, Ellery F, English C, et al.
    Int J Stroke, 2023 Jul;18(6):745-750.
    PMID: 36398582 DOI: 10.1177/17474930221142207
    RATIONALE: The evidence base for acute post-stroke rehabilitation is inadequate and global guideline recommendations vary.

    AIM: To define optimal early mobility intervention regimens for ischemic stroke patients of mild and moderate severity.

    HYPOTHESES: Compared with a prespecified reference arm, the optimal dose regimen(s) will result in more participants experiencing little or no disability (mRS 0-2) at 3 months post-stroke (primary), fewer deaths at 3 months, fewer and less severe complications during the intervention period, faster recovery of unassisted walking, and better quality of life at 3 months (secondary). We also hypothesize that these regimens will be more cost-effective.

    SAMPLE SIZE ESTIMATES: For the primary outcome, recruitment of 1300 mild and 1400 moderate participants will yield 80% power to detect a 10% risk difference.

    METHODS AND DESIGN: Multi-arm multi-stage covariate-adjusted response-adaptive randomized trial of mobility training commenced within 48 h of stroke in mild (NIHSS  2) and hemorrhagic stroke. With four arms per stratum (reference arm retained throughout), only the single treatment arm demonstrating the highest proportion of favorable outcomes at the first stage will proceed to the second stage in each stratum, resulting in a final comparison with the reference arm. Three prognostic covariates of age, geographic region and reperfusion interventions, as well as previously observed mRS 0-2 responses inform the adaptive randomization procedure. Participants randomized receive prespecified mobility training regimens (functional task-specific), provided by physiotherapists/nurses until discharge or 14 days. Interventions replace usual mobility training. Fifty hospitals in seven countries (Australia, Malaysia, United Kingdom, Ireland, India, Brazil, Singapore) are expected to participate.

    SUMMARY: Our novel adaptive trial design will evaluate a wider variety of mobility regimes than a traditional two-arm design. The data-driven adaptions during the trial will enable a more efficient evaluation to determine the optimal early mobility intervention for patients with mild and moderate ischemic stroke.

    Matched MeSH terms: Humans
  6. Blaauw M, Ridikas D, Baytelesov S, Salas PS, Chakrova Y, Eun-Ha C, et al.
    J Radioanal Nucl Chem, 2017;311(1):409-418.
    PMID: 28111485 DOI: 10.1007/s10967-016-5036-6
    Molybdenum-99 is one of the most important radionuclides for medical diagnostics. In 2015, the International Atomic Energy Agency organized a round-robin exercise where the participants measured and calculated specific saturation activities achievable for the (98)Mo(n,γ)(99)Mo reaction. This reaction is of interest as a means to locally, and on a small scale, produce (99)Mo from natural molybdenum. The current paper summarises a set of experimental results and reviews the methodology for calculating the corresponding saturation activities. Activation by epithermal neutrons and also epithermal neutron self-shielding are found to be of high importance in this case.
    Matched MeSH terms: Humans
  7. Khan PA, Johl SK, Kumar A, Luthra S
    Environ Sci Pollut Res Int, 2023 Apr;30(19):55237-55254.
    PMID: 36882655 DOI: 10.1007/s11356-023-26262-4
    The current production and conception have impacted the environmental hazards. Green innovation (GI) is the ideal solution for sustainable production, consumption, and ecological conservation. The objective of the study is to compare comprehensive green innovation (green product, process, service, and organization) impact on firm financial performance in Malaysia and Indonesia, along with the first study to measure the moderation role of the corporate governance index. This study has addressed the gap by developing the green innovation and corporate governance index. Collected panel data from the top 188 publicly listed firms for 3 years and analyzed it using the general least square method. The empirical evidence demonstrates that the green innovation practice is better in Malaysia, and the outcome also shows that the significance level is higher in Indonesia. This study also provides empirical evidence that board composition has a positive moderation relationship betwixt GI and business performance in Malaysia but is insignificant in Indonesia. This comparative study provides new insights to the policymakers and practitioners of both countries to monitor and manage green innovation practices.
    Matched MeSH terms: Humans
  8. Inoue K, Chieh JTW, Yeh LC, Chiang SJ, Phrommintikul A, Suwanasom P, et al.
    Trials, 2022 Dec 07;23(1):986.
    PMID: 36476401 DOI: 10.1186/s13063-022-06907-4
    BACKGROUND: More than half of the world's population lives in Asia. With current life expectancies in Asian countries, the burden of cardiovascular disease is increasing exponentially. Overcrowding in the emergency departments (ED) has become a public health problem. Since 2015, the European Society of Cardiology recommends the use of a 0/1-h algorithm based on high-sensitivity cardiac troponin (hs-cTn) for rapid triage of patients with suspected non-ST elevation acute coronary syndrome (NSTE-ACS). However, these algorithms are currently not recommended by Asian guidelines due to the lack of suitable data.

    METHODS: The DROP-Asian ACS is a prospective, stepped wedge, cluster-randomized trial enrolling 4260 participants presenting with chest pain to the ED of 12 acute care hospitals in five Asian countries (UMIN; 000042461). Consecutive patients presenting with suspected acute coronary syndrome between July 2022 and Apr 2024 were included. Initially, all clusters will apply "usual care" according to local standard operating procedures including hs-cTnT but not the 0/1-h algorithm. The primary outcome is the incidence of major adverse cardiac events (MACE), the composite of all-cause death, myocardial infarction, unstable angina, or unplanned revascularization within 30 days. The difference in MACE (with one-sided 95% CI) was estimated to evaluate non-inferiority. The non-inferiority margin was prespecified at 1.5%. Secondary efficacy outcomes include costs for healthcare resources and duration of stay in ED.

    CONCLUSIONS: This study provides important evidence concerning the safety and efficacy of the 0/1-h algorithm in Asian countries and may help to reduce congestion of the ED as well as medical costs.

    Matched MeSH terms: Humans
  9. Karuppaiah A, Selvaraj D, Sellappan M, Nagarajan A, Babu D, Rahman H, et al.
    Curr Pharm Des, 2023;29(4):239-245.
    PMID: 36624648 DOI: 10.2174/1381612829666230109111635
    Metallic nanoparticles (MNPs) have been widely used for diagnostic and therapeutic purposes in clinical practice. A number of MNP formulations are being investigated in clinical trials for various applications. This increase in the use of NPs results in higher exposure to humans, leading to toxicity issues. Hence, it is necessary to determine the possible undesirable effects of the MNPs after in-vivo application and exposure. One of the main reasons for the toxicity of MNPs is the release of their respective metallic ions throughout the body. Many research studies are in progress investigating the various strategies to reduce the toxicity of MNPs. These research studies aim to change the size, dose, agglomeration, release, and excretion rates of MNPs. In this perspective review, we discussed the possible strategies to improve the therapeutic effects of MNPs through various processes, with lessons learned from the studies involving silver nanoparticles (AgNPs). We also discussed the ways to manage the toxicity of MNPs by purification, surface functionalization, synergistic effect, and targeted therapy approach. All these strategies could reduce the dose of the MNPs without compromising their therapeutic benefits, which could decrease the toxicity of MNPs. Additionally, we briefly discussed the market and toxicology testing for FDA-regulated MNPs.
    Matched MeSH terms: Humans
  10. Tan SP, Ng LC, Lyndon N, Aman Z, Kannan P, Hashim K, et al.
    PeerJ, 2023;11:e15228.
    PMID: 37151297 DOI: 10.7717/peerj.15228
    BACKGROUND: Malaysia is strongly supported by the agriculture sector as the backbone to drive the economy. However, COVID-19 has significantly affected agriculture across the production, supply, and marketing chains. It also disturbs the balance of food supply and demand in Malaysia. COVID-19 was an unexpected pandemic that resulted in shock and panic and caused a huge global impact. However, the impacts of this pandemic on the agriculture sector in Malaysia, particularly in the production and supply chains, are still unclear and scarce. This review offers insights into the challenges, particularly in sustaining agri-food production and supply chains. It also highlights the opportunity and relevant measures towards sustainability in agriculture to avoid agri-food disasters in the future.

    METHODS: This study was carried out through a desk review of the secondary source of information covering the impact of COVID-19 in Malaysia particularly in the agri-food aspect, and a wide range of strategies and initiatives as the effective measures to overcome the crisis of this pandemic. Online desk research of the government published data and customer desk research were utilized to complete this study. Search engines such as Google Scholar and the statistical data from the official websites including the Department of Statistics Malaysia (DOSM) and the Food and Fertilizer Technology Center for the Asian and Pacific Region (FFTC-AP), were utilized. Keywords such as impact of COVID-19, pandemic, and agri-food supply chain were used to conduct the searches. The articles identified to be related to the study's objective were then downloaded and included in the study. Descriptive methods were used as the primary analysis technique following the descriptive analysis and visual data analysis in performing the sources obtained.

    RESULTS: This devastating impact damages the lives by causing 4.3 million confirmed infections and more than 290,000 deaths. This disease presents an unprecedented challenge to the public health. The lockdown restriction under the movement control order (MCO), for more than of the world's population in the year 2020 to control the virus from spreading, has disrupted most of the economic sectors. The agriculture industry was seen as one of the essential industries and allowed to operate under strict standard operating procedures (SOP). Working under strict regulations came with a huge price paid for almost all industries.

    CONCLUSION: This pandemic has affected the national agri-food availability and accessibility in Malaysia. This outbreak created a reflection of opportunity for sharing a more flexible approaches in handling emergencies on agricultural food production and supply chains. Therefore, the government should be ready with the roadmap and enforce the measures to control the pandemic without disrupting the agri-food supply chain in the near future.

    Matched MeSH terms: Humans
  11. Tan CW, Gamage AM, Yap WC, Wei Tang LJ, Sun Y, Yang XL, et al.
    Emerg Microbes Infect, 2023 Dec;12(1):2208683.
    PMID: 37143369 DOI: 10.1080/22221751.2023.2208683
    Pteropine orthoreoviruses (PRVs) are an emerging group of fusogenic, bat-borne viruses from the Orthoreovirus genus. Since the isolation of PRV from a patient with acute respiratory tract infections in 2006, the zoonotic potential of PRV has been further highlighted following subsequent isolation of PRV species from patients in Malaysia, Hong Kong and Indonesia. However, the entry mechanism of PRV is currently unknown. In this study, we investigated the role of previously identified mammalian orthoreovirus (MRV) receptors, sialic acid and junctional adhesion molecule-1 for PRV infection. However, none of these receptors played a significant role in PRV infection, suggesting PRV uses a distinct entry receptor from MRV. Given its broad tissue tropism, we hypothesized that PRV may use a receptor that is widely expressed in all cell types, heparan sulphate (HS). Enzymatic removal of cell surface HS by heparinase treatment and genetic ablation of HS biosynthesis genes, SLC35B2, exostosin-1, N-deacetylase/N-sulfotransferase I and beta-1,3-glucuronyltransferase 3, significantly reduced infection with multiple genetically distinct PRV species. Replication kinetic of PRV3M in HS knockout cells revealed that HS plays a crucial role in the early phase of PRV infection. Mechanistic studies demonstrated that HS is an essential host-factor for PRV attachment and internalization into cells. To our knowledge, this is the first report on the use of HS as an attachment receptor by PRVs.
    Matched MeSH terms: Humans
  12. Majeed MA, Shafri HZM, Zulkafli Z, Wayayok A
    PMID: 36901139 DOI: 10.3390/ijerph20054130
    This research aims to predict dengue fever cases in Malaysia using machine learning techniques. A dataset consisting of weekly dengue cases at the state level in Malaysia from 2010 to 2016 was obtained from the Malaysia Open Data website and includes variables such as climate, geography, and demographics. Six different long short-term memory (LSTM) models were developed and compared for dengue prediction in Malaysia: LSTM, stacked LSTM (S-LSTM), LSTM with temporal attention (TA-LSTM), S-LSTM with temporal attention (STA-LSTM), LSTM with spatial attention (SA-LSTM), and S-LSTM with spatial attention (SSA-LSTM). The models were trained and evaluated on a dataset of monthly dengue cases in Malaysia from 2010 to 2016, with the task of predicting the number of dengue cases based on various climate, topographic, demographic, and land-use variables. The SSA-LSTM model, which used both stacked LSTM layers and spatial attention, performed the best, with an average root mean squared error (RMSE) of 3.17 across all lookback periods. When compared to three benchmark models (SVM, DT, ANN), the SSA-LSTM model had a significantly lower average RMSE. The SSA-LSTM model also performed well in different states in Malaysia, with RMSE values ranging from 2.91 to 4.55. When comparing temporal and spatial attention models, the spatial models generally performed better at predicting dengue cases. The SSA-LSTM model was also found to perform well at different prediction horizons, with the lowest RMSE at 4- and 5-month lookback periods. Overall, the results suggest that the SSA-LSTM model is effective at predicting dengue cases in Malaysia.
    Matched MeSH terms: Humans
  13. Baashar Y, Alkawsi G, Wan Ahmad WN, Alomari MA, Alhussian H, Tiong SK
    PMID: 36900951 DOI: 10.3390/ijerph20053940
    Head-mounted displays (HMDs) have the potential to greatly impact the surgical field by maintaining sterile conditions in healthcare environments. Google Glass (GG) and Microsoft HoloLens (MH) are examples of optical HMDs. In this comparative survey related to wearable augmented reality (AR) technology in the medical field, we examine the current developments in wearable AR technology, as well as the medical aspects, with a specific emphasis on smart glasses and HoloLens. The authors searched recent articles (between 2017 and 2022) in the PubMed, Web of Science, Scopus, and ScienceDirect databases and a total of 37 relevant studies were considered for this analysis. The selected studies were divided into two main groups; 15 of the studies (around 41%) focused on smart glasses (e.g., Google Glass) and 22 (59%) focused on Microsoft HoloLens. Google Glass was used in various surgical specialities and preoperative settings, namely dermatology visits and nursing skill training. Moreover, Microsoft HoloLens was used in telepresence applications and holographic navigation of shoulder and gait impairment rehabilitation, among others. However, some limitations were associated with their use, such as low battery life, limited memory size, and possible ocular pain. Promising results were obtained by different studies regarding the feasibility, usability, and acceptability of using both Google Glass and Microsoft HoloLens in patient-centric settings as well as medical education and training. Further work and development of rigorous research designs are required to evaluate the efficacy and cost-effectiveness of wearable AR devices in the future.
    Matched MeSH terms: Humans
  14. Vaithilingam S, Hwang LA, Nair M, Ng JWJ, Ahmed P, Musa KI
    PLoS One, 2023;18(3):e0282520.
    PMID: 36920970 DOI: 10.1371/journal.pone.0282520
    BACKGROUND: Sporadic outbreaks of COVID-19 remain a threat to public healthcare, especially if vaccination levels do not improve. As Malaysia begins its transition into the endemic phase, it is essential to identify the key determinants of COVID-19 vaccination intention amongst the pockets of the population who are still hesitant. Therefore, focusing on a sample of individuals who did not register for the COVID-19 vaccination, the current study integrated two widely used frameworks in the public health domain-the health belief model (HBM) and the theory of reasoned action (TRA)-to examine the inter-relationships of the predictors of vaccination intention amongst these individuals.

    METHODOLOGY: Primary data from 117 respondents who did not register for the COVID-19 vaccination were collected using self-administered questionnaires to capture predictors of vaccination intention amongst individuals in a Malaysian context. The partial least squares structural equation modeling (PLS-SEM) technique was used to analyze the data.

    RESULTS: Subjective norms and attitude play key mediating roles between the HBM factors and vaccination intention amongst the unregistered respondents. In particular, subjective norms mediate the relationship between cues to action and vaccination intention, highlighting the significance of important others to influence unregistered individuals who are already exposed to information from mass media and interpersonal discussions regarding vaccines. Trust, perceived susceptibility, and perceived benefits indirectly influence vaccination intention through attitude, indicating that one's attitude is vital in promoting behavioral change.

    CONCLUSION: This study showed that the behavioral factors could help understand the reasons for vaccine refusal or acceptance, and shape and improve health interventions, particularly among the vaccine-hesitant group in a developing country. Therefore, policymakers and key stakeholders can develop effective strategies or interventions to encourage vaccination amongst the unvaccinated for future health pandemics by targeting subjective norms and attitude.

    Matched MeSH terms: Humans
  15. Chuah LH, Loo HL, Goh CF, Fu JY, Ng SF
    Drug Deliv Transl Res, 2023 May;13(5):1436-1455.
    PMID: 36808298 DOI: 10.1007/s13346-023-01307-w
    Atopic dermatitis (AD) is a complex, relapsing inflammatory skin disease with a considerable social and economic burden globally. AD is primarily characterized by its chronic pattern and it can have important modifications in the quality of life of the patients and caretakers. One of the fastest-growing topics in translational medicine today is the exploration of new or repurposed functional biomaterials into drug delivery therapeutic applications. This area has gained a considerable amount of research which produced many innovative drug delivery systems for inflammatory skin diseases like AD. Chitosan, a polysaccharide, has attracted attention as a functional biopolymer for diverse applications, especially in pharmaceutics and medicine, and has been considered a promising candidate for AD treatment due to its antimicrobial, antioxidative, and inflammatory response modulation properties. The current pharmacological treatment for AD involves prescribing topical corticosteroid and calcineurin inhibitors. However, the adverse reactions associated with the long-term usage of these drugs such as itching, burning, or stinging sensation are also well documented. Innovative formulation strategies, including the use of micro- and nanoparticulate systems, biopolymer hydrogel composites, nanofibers, and textile fabrication are being extensively researched with an aim to produce a safe and effective delivery system for AD treatment with minimal side effects. This review outlines the recent development of various chitosan-based drug delivery systems for the treatment of AD published in the past 10 years (2012-2022). These chitosan-based delivery systems include hydrogels, films, micro-, and nanoparticulate systems as well as chitosan textile. The global patent trends on chitosan-based formulations for the AD are also discussed.
    Matched MeSH terms: Humans
  16. Leung HK, Mahadeva S, Rajaram RB, Lai PSM
    Eur J Gastroenterol Hepatol, 2023 Mar 01;35(3):333-341.
    PMID: 36708305 DOI: 10.1097/MEG.0000000000002493
    BACKGROUND: Assessing a patient's knowledge regarding liver cirrhosis is important to improve patient outcomes. This study aimed to develop and validate the Adult cirrhosiS Knowledge Questionnaire (ASK-Q) to assess patients' knowledge regarding liver cirrhosis from multiple aspects.

    METHODS: A 24-item ASK-Q with four domains: self-understanding (5 items), aetiology (5 items), complications (5 items) and management (9 items) of liver cirrhosis was developed based on literature review and expert panel input. It was then piloted in five English-speaking patients with liver cirrhosis. These patients commented that the font size was too small. Hence, the font was enlarged and the final version of the ASK-Q was administered to English-speaking patients with liver cirrhosis, aged ≥18 years, with or without decompensation, at a tertiary hospital, from September 2020 to November 2021, at baseline and fortnight later. Patients with encephalopathy were excluded.

    RESULTS: 120/135 patients agreed to participate (response rate = 88.9%). The overall median score was 59.1 (45.6-68.2). A total of 7/22 (31.8%) items were "easy", 14/22 (63.6%) items were "moderately easy" and 1/22 (4.5%) items were "difficult". Exploratory factor analysis extracted nine factors, and two items were omitted. The ASK-Q was able to discriminate the knowledge level of patients with and without tertiary education [59.1 (50.0-72.7) vs. 54.5 (36.4-63.6); P 

    Matched MeSH terms: Humans
  17. Wang Y, Liu X, Dong L, Cheng KK, Lin C, Wang X, et al.
    Anal Chem, 2023 Apr 18;95(15):6203-6211.
    PMID: 37023366 DOI: 10.1021/acs.analchem.2c04603
    Drug combinations are commonly used to treat various diseases to achieve synergistic therapeutic effects or to alleviate drug resistance. Nevertheless, some drug combinations might lead to adverse effects, and thus, it is crucial to explore the mechanisms of drug interactions before clinical treatment. Generally, drug interactions have been studied using nonclinical pharmacokinetics, toxicology, and pharmacology. Here, we propose a complementary strategy based on metabolomics, which we call interaction metabolite set enrichment analysis, or iMSEA, to decipher drug interactions. First, a digraph-based heterogeneous network model was constructed to model the biological metabolic network based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Second, treatment-specific influences on all detected metabolites were calculated and propagated across the whole network model. Third, pathway activity was defined and enriched to quantify the influence of each treatment on the predefined functional metabolite sets, i.e., metabolic pathways. Finally, drug interactions were identified by comparing the pathway activity enriched by the drug combination treatments and the single drug treatments. A data set consisting of hepatocellular carcinoma (HCC) cells that were treated with oxaliplatin (OXA) and/or vitamin C (VC) was used to illustrate the effectiveness of the iMSEA strategy for evaluation of drug interactions. Performance evaluation using synthetic noise data was also performed to evaluate sensitivities and parameter settings for the iMSEA strategy. The iMSEA strategy highlighted synergistic effects of combined OXA and VC treatments including the alterations in the glycerophospholipid metabolism pathway and glycine, serine, and threonine metabolism pathway. This work provides an alternative method to reveal the mechanisms of drug combinations from the viewpoint of metabolomics.
    Matched MeSH terms: Humans
  18. Karajacob AS, Azizan NB, Al-Maleki ARM, Goh JPE, Loke MF, Khor HM, et al.
    PLoS One, 2023;18(4):e0284043.
    PMID: 37068057 DOI: 10.1371/journal.pone.0284043
    Overgrowth of Candida yeasts in the oral cavity may result in the development of oral thrush in immunocompromised individuals. This study analyzed the diversity and richness of the oral mycobiota of patients clinically diagnosed with oral thrush (OT), follow-up of oral thrush patients after antifungal therapy (AT), and healthy controls (HC). Oral rinse and oral swab samples were collected from 38 OT patients, 21 AT patients, and 41 healthy individuals (HC). Pellet from the oral rinse and oral swab were used for the isolation of oral Candida yeasts on Brilliance Candida Agar followed by molecular speciation. ITS1 amplicon sequencing using Illumina MiSeq was performed on DNA extracted from the oral rinse pellet of 16 OT, 7 AT, and 7 HC oral rinse samples. Trimmed sequence data were taxonomically grouped and analyzed using the CLC Microbial Genomics Module workflow. Candida yeasts were isolated at significantly higher rates from oral rinse and swab samples of OT (68.4%, p < 0.001) and AT (61.9%, p = 0.012) patients, as compared to HC (26.8%). Predominance of Candida albicans specifically, was noted in OT (60.5%, p < 0.001) and AT (42.9%, p = 0.006) vs. HC (9.8%), while non-albicans Candida species was dominant in HC. Analysis of oral mycobiota from OT patients showed the presence of 8 phyla, 222 genera, and 309 fungal species. Low alpha diversity (Shannon index, p = 0.006; Chao-1 biased corrected index, p = 0.01), varied beta diversity (Bray-Curtis, p = 0.01986; Jaccard, p = 0.02766; Weighted UniFrac, p = 0.00528), and increased relative abundance of C. albicans (p = 3.18E-02) was significantly associated with the oral mycobiota of OT vs. HC. This study supported that C. albicans is the main etiological agent in oral thrush and highlights the association of fungal biodiversity with the pathophysiology of oral thrush.
    Matched MeSH terms: Humans
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