Displaying publications 541 - 560 of 1087 in total

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  1. Lan NSR, Chih H, Brennan AL, Dwivedi G, Figtree GA, Dinh D, et al.
    PMID: 39248198 DOI: 10.1002/ccd.31205
    BACKGROUND: Among ST-elevation myocardial infarction (STEMI) patients, those with no standard modifiable risk factors (SMuRFs: hypertension, diabetes mellitus, hypercholesterolemia, and smoking) have higher 30-day mortality than those with SMuRFs. Differences in coronary lesion characteristics remain unclear.

    METHODS: Data from STEMI patients aged ≤60 years from the Asia Pacific Evaluation of Cardiovascular Therapies Network (Australia, Hong Kong, Malaysia, Singapore, and Vietnam) was retrospectively analysed. Exclusion criteria included incomplete SMuRF data, prior myocardial infarction, or prior coronary revascularisation. Lesion type was defined using the American College of Cardiology criteria. Major adverse cardiovascular events (MACE) were defined as peri-procedural myocardial infarction, emergency coronary artery bypass surgery, cerebrovascular event, or mortality. Multiple logistic regressions were used.

    RESULTS: Of 4404 patients, 767 (17.4%) were SMuRFless. SMuRFless patients were more frequently younger (median age 51 vs. 53 years; p 

  2. Arn Ng Q, Yew Shuen Ang C, Shiong Chiew Y, Wang X, Pin Tan C, Basri Mat Nor M, et al.
    HardwareX, 2022 Oct;12:e00358.
    PMID: 36117541 DOI: 10.1016/j.ohx.2022.e00358
    Mechanical ventilation (MV) provides respiratory support for critically ill patients in the intensive care unit (ICU). Waveform data output by the ventilator provides valuable physiological and diagnostic information. However, existing systems do not provide full access to this information nor allow for real-time, non-invasive data collection. Therefore, large amounts of data are lost and analysis is limited to short samples of breathing cycles. This study presents a data acquisition device for acquiring and monitoring patient ventilation waveform data. Acquired data can be exported to other systems, allowing users to further analyse data and develop further clinically useful parameters. These parameters, together with other ventilatory information, can help personalise and guide MV treatment. The device is designed to be easily replicable, low-cost, and scalable according to the number of patient beds. Validation was carried out by assessing system performance and stability over prolonged periods of 7 days of continuous use. The device provides a platform for future integration of machine-learning or model-based modules, potentially allowing real-time, proactive, patient-specific MV guidance and decision support to improve the quality and productivity of care and outcomes.
  3. Notz Q, Lee ZY, Menger J, Elke G, Hill A, Kranke P, et al.
    Crit Care, 2022 01 19;26(1):23.
    PMID: 35045885 DOI: 10.1186/s13054-022-03896-3
    BACKGROUND: Parenteral lipid emulsions in critical care are traditionally based on soybean oil (SO) and rich in pro-inflammatory omega-6 fatty acids (FAs). Parenteral nutrition (PN) strategies with the aim of reducing omega-6 FAs may potentially decrease the morbidity and mortality in critically ill patients.

    METHODS: A systematic search of MEDLINE, EMBASE, CINAHL and CENTRAL was conducted to identify all randomized controlled trials in critically ill patients published from inception to June 2021, which investigated clinical omega-6 sparing effects. Two independent reviewers extracted bias risk, treatment details, patient characteristics and clinical outcomes. Random effect meta-analysis was performed.

    RESULTS: 1054 studies were identified in our electronic search, 136 trials were assessed for eligibility and 26 trials with 1733 critically ill patients were included. The median methodologic score was 9 out of 14 points (95% confidence interval [CI] 7, 10). Omega-6 FA sparing PN in comparison with traditional lipid emulsions did not decrease overall mortality (20 studies; risk ratio [RR] 0.91; 95% CI 0.76, 1.10; p = 0.34) but hospital length of stay was substantially reduced (6 studies; weighted mean difference [WMD] - 6.88; 95% CI - 11.27, - 2.49; p = 0.002). Among the different lipid emulsions, fish oil (FO) containing PN reduced the length of intensive care (8 studies; WMD - 3.53; 95% CI - 6.16, - 0.90; p = 0.009) and rate of infectious complications (4 studies; RR 0.65; 95% CI 0.44, 0.95; p = 0.03). When FO was administered as a stand-alone medication outside PN, potential mortality benefits were observed compared to standard care.

    CONCLUSION: Overall, these findings highlight distinctive omega-6 sparing effects attributed to PN. Among the different lipid emulsions, FO in combination with PN or as a stand-alone treatment may have the greatest clinical impact. Trial registration PROSPERO international prospective database of systematic reviews (CRD42021259238).

  4. Koh CMM, Ping LSY, Xuan CHH, Theng LB, San HS, Palombo EA, et al.
    Bioengineered, 2023 Dec;14(1):2243416.
    PMID: 37552115 DOI: 10.1080/21655979.2023.2243416
    The rampant spread of multidrug-resistant Pseudomonas aeruginosa strains severely threatens global health. This severity is compounded against the backdrop of a stagnating antibiotics development pipeline. Moreover, with many promising therapeutics falling short of expectations in clinical trials, targeting the las quorum sensing (QS) system remains an attractive therapeutic strategy to combat P. aeruginosa infection. Thus, our primary goal was to develop a drug prediction algorithm using machine learning to identify potent LasR inhibitors. In this work, we demonstrated using a Multilayer Perceptron (MLP) algorithm boosted with AdaBoostM1 to discriminate between active and inactive LasR inhibitors. The optimal model performance was evaluated using 5-fold cross-validation and test sets. Our best model achieved a 90.7% accuracy in distinguishing active from inactive LasR inhibitors, an area under the Receiver Operating Characteristic Curve value of 0.95, and a Matthews correlation coefficient value of 0.81 when evaluated using test sets. Subsequently, we deployed the model against the Enamine database. The top-ranked compounds were further evaluated for their target engagement activity using molecular docking studies, Molecular Dynamics simulations, MM-GBSA analysis, and Free Energy Landscape analysis. Our data indicate that several of our chosen top hits showed better ligand-binding affinities than naringenin, a competitive LasR inhibitor. Among the six top hits, five of these compounds were predicted to be LasR inhibitors that could be used to treat P. aeruginosa-associated infections. To our knowledge, this study provides the first assessment of using an MLP-based QSAR model for discovering potent LasR inhibitors to attenuate P. aeruginosa infections.
  5. Main BJ, Nicholson J, Winokur OC, Steiner C, Riemersma KK, Stuart J, et al.
    PLoS Negl Trop Dis, 2018 Jun;12(6):e0006524.
    PMID: 29927940 DOI: 10.1371/journal.pntd.0006524
    Zika virus (ZIKV) has emerged since 2013 as a significant global human health threat following outbreaks in the Pacific Islands and rapid spread throughout South and Central America. Severe congenital and neurological sequelae have been linked to ZIKV infections. Assessing the ability of common mosquito species to transmit ZIKV and characterizing variation in mosquito transmission of different ZIKV strains is important for estimating regional outbreak potential and for prioritizing local mosquito control strategies for Aedes and Culex species. In this study, we evaluated the laboratory vector competence of Aedes aegypti, Culex quinquefasciatus, and Culex tarsalis that originated in areas of California where ZIKV cases in travelers since 2015 were frequent. We compared infection, dissemination, and transmission rates by measuring ZIKV RNA levels in cohorts of mosquitoes that ingested blood meals from type I interferon-deficient mice infected with either a Puerto Rican ZIKV strain from 2015 (PR15), a Brazilian ZIKV strain from 2015 (BR15), or an ancestral Asian-lineage Malaysian ZIKV strain from 1966 (MA66). With PR15, Cx. quinquefasciatus was refractory to infection (0%, N = 42) and Cx. tarsalis was infected at 4% (N = 46). No ZIKV RNA was detected in saliva from either Culex species 14 or 21 days post feeding (dpf). In contrast, Ae. aegypti developed infection rates of 85% (PR15; N = 46), 90% (BR15; N = 20), and 81% (MA66; N = 85) 14 or 15 dpf. Although MA66-infected Ae. aegypti showed higher levels of ZIKV RNA in mosquito bodies and legs, transmission rates were not significantly different across virus strains (P = 0.13, Fisher's exact test). To confirm infectivity and measure the transmitted ZIKV dose, we enumerated infectious ZIKV in Ae. aegypti saliva using Vero cell plaque assays. The expectorated plaque forming units PFU varied by viral strain: MA66-infected expectorated 13±4 PFU (mean±SE, N = 13) compared to 29±6 PFU for PR15-infected (N = 13) and 35±8 PFU for BR15-infected (N = 6; ANOVA, df = 2, F = 3.8, P = 0.035). These laboratory vector competence results support an emerging consensus that Cx. tarsalis and Cx. quinquefasciatus are not vectors of ZIKV. These results also indicate that Ae. aegypti from California are efficient laboratory vectors of ancestral and contemporary Asian lineage ZIKV.
  6. Ang CYS, Chiew YS, Wang X, Ooi EH, Nor MBM, Cove ME, et al.
    Comput Methods Programs Biomed, 2023 Oct;240:107728.
    PMID: 37531693 DOI: 10.1016/j.cmpb.2023.107728
    BACKGROUND AND OBJECTIVE: Healthcare datasets are plagued by issues of data scarcity and class imbalance. Clinically validated virtual patient (VP) models can provide accurate in-silico representations of real patients and thus a means for synthetic data generation in hospital critical care settings. This research presents a realistic, time-varying mechanically ventilated respiratory failure VP profile synthesised using a stochastic model.

    METHODS: A stochastic model was developed using respiratory elastance (Ers) data from two clinical cohorts and averaged over 30-minute time intervals. The stochastic model was used to generate future Ers data based on current Ers values with added normally distributed random noise. Self-validation of the VPs was performed via Monte Carlo simulation and retrospective Ers profile fitting. A stochastic VP cohort of temporal Ers evolution was synthesised and then compared to an independent retrospective patient cohort data in a virtual trial across several measured patient responses, where similarity of profiles validates the realism of stochastic model generated VP profiles.

    RESULTS: A total of 120,000 3-hour VPs for pressure control (PC) and volume control (VC) ventilation modes are generated using stochastic simulation. Optimisation of the stochastic simulation process yields an ideal noise percentage of 5-10% and simulation iteration of 200,000 iterations, allowing the simulation of a realistic and diverse set of Ers profiles. Results of self-validation show the retrospective Ers profiles were able to be recreated accurately with a mean squared error of only 0.099 [0.009-0.790]% for the PC cohort and 0.051 [0.030-0.126]% for the VC cohort. A virtual trial demonstrates the ability of the stochastic VP cohort to capture Ers trends within and beyond the retrospective patient cohort providing cohort-level validation.

    CONCLUSION: VPs capable of temporal evolution demonstrate feasibility for use in designing, developing, and optimising bedside MV guidance protocols through in-silico simulation and validation. Overall, the temporal VPs developed using stochastic simulation alleviate the need for lengthy, resource intensive, high cost clinical trials, while facilitating statistically robust virtual trials, ultimately leading to improved patient care and outcomes in mechanical ventilation.

  7. Alregib AH, Tan HY, Wong YH, Kasbollah A, Wong EH, Abdullah BJJ, et al.
    J Labelled Comp Radiopharm, 2023 Aug;66(10):308-320.
    PMID: 37287213 DOI: 10.1002/jlcr.4046
    Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are promising treatments for unresectable liver tumours. Some recent studies suggested that combining TACE and TARE in one treatment course might improve treatment efficacy through synergistic cytotoxicity effects. Nonetheless, current formulations do not facilitate a combination of chemo- and radio-embolic agents in one delivery system. Therefore, this study aimed to synthesise a hybrid biodegradable microsphere loaded with both radioactive agent, samarium-153 (153 Sm) and chemotherapeutic drug, doxorubicin (Dox) for potential radio-chemoembolization of advanced liver tumours. 152 Sm and Dox-loaded polyhydroxybutyrate-co-3-hydroxyvalerate (PHBV) microspheres were prepared using water-in-oil-in-water solvent evaporation method. The microspheres were then sent for neutron activation in a neutron flux of 2 × 1012  n/cm2 /s. The physicochemical properties, radioactivity, radionuclide purity, 153 Sm retention efficiency, and Dox release profile of the Dox-153 Sm-PHBV microspheres were analysed. In addition, in vitro cytotoxicity of the formulation was tested using MTT assay on HepG2 cell line at 24 and 72 h. The mean diameter of the Dox-153 Sm-PHBV microspheres was 30.08 ± 2.79 μm. The specific radioactivity was 8.68 ± 0.17 GBq/g, or 177.69 Bq per microsphere. The 153 Sm retention efficiency was more than 99%, tested in phosphate-buffered saline (PBS) and human blood plasma over 26 days. The cumulative release of Dox from the microspheres after 41 days was 65.21 ± 1.96% and 29.96 ± 0.03% in PBS solution of pH 7.4 and pH 5.5, respectively. The Dox-153 Sm-PHBV microspheres achieved a greater in vitro cytotoxicity effect on HepG2 cells (85.73 ± 3.63%) than 153 Sm-PHBV (70.03 ± 5.61%) and Dox-PHBV (74.06 ± 0.78%) microspheres at 300 μg/mL at 72 h. In conclusion, a novel biodegradable microspheres formulation loaded with chemotherapeutic drug (Dox) and radioactive agent (153 Sm) was successfully developed in this study. The formulation fulfilled all the desired physicochemical properties of a chemo-radioembolic agent and achieved better in vitro cytotoxicity on HepG2 cells. Further investigations are needed to evaluate the biosafety, radiation dosimetry, and synergetic anticancer properties of the formulation.
  8. Choon SE, Wright AK, Griffiths CEM, Wong KW, Tey KE, Lim YT, et al.
    Br J Dermatol, 2023 Sep 15;189(4):410-418.
    PMID: 37162007 DOI: 10.1093/bjd/ljad158
    BACKGROUND: There is limited understanding of the epidemiology of generalized pustular psoriasis (GPP) internationally, with no population-based estimates of GPP in South East Asia.

    OBJECTIVES: To determine the incidence and prevalence of GPP in the Malaysian population and characterize its flares and trigger factors.

    METHODS: We conducted a population-based cohort study using the Teleprimary Care database between January 2010 and December 2020. We identified 230 dermatologist-confirmed GPP cases using International Classification of Diseases, 10th revision, diagnostic codes. Annual prevalence and incidence rates were stratified by age, sex and ethnicity. We compared data regarding flares and trigger factors for patients with GPP who had associated psoriasis vulgaris (PV) with those who did not have associated PV.

    RESULTS: The prevalence of GPP was 198 per million (267 women, 127 men) and incidence was 27.2 per million person-years [95% confidence interval (CI) 22.8-31.6]; 35.3 (28.4-42.2) per million person-years for women and 18.3 (13.1-23.5) per million person-years for men. Rates were higher in Chinese individuals [prevalence 271 per million; incidence 41.6 per million person-years (28.9-54.3)] than in the Malay population [prevalence 186; incidence 24.6 (19.4-29.7)] or the Indian ethnic group [prevalence 179; incidence 25.0 (13.8-36.3)]. Annual prevalence was consistently higher in women than in men and highest among the Chinese population, followed by the Indian and Malay populations. Overall, 67% of patients with GPP had associated PV. The prevalence and incidence of GPP without PV were lower than GPP with PV at 66 vs. 132 per million and 19.3 (95% CI 15.6-23.0) vs. 8.0 (95% CI 5.6-10.3) per million person-years, respectively. The mean age at GPP onset was 42.7 years (SD 18.4). A bimodal trend in the age of GPP onset was observed, with first and second peaks at age 20-29 years and age 50-59 years, respectively. Disease onset was significantly earlier in patients with GPP without PV than in those with PV [mean age 37.5 years (SD 20.7) vs. 44.9 years (SD 17.0), P = 0.026]. Flares occurred more frequently in patients without PV than in those with PV [mean number of flares per patient per year was 1.35 (SD 0.77) vs. 1.25 (SD 0.58), P = 0.039]. Common triggers of flares in patients with GPP who did not have PV were infections, pregnancy, menstruation and stress, whereas withdrawal of therapy, particularly systemic corticosteroids, was a more frequent trigger in patients with GPP who also had PV.

    CONCLUSIONS: Our findings contribute to the global mapping of GPP, which will help inform the management of this rare condition.

  9. Su TT, Adekunjo FO, Schliemann D, Cardwell CR, Htay MNN, Dahlui M, et al.
    BMJ Open, 2023 Aug 31;13(8):e072166.
    PMID: 37652591 DOI: 10.1136/bmjopen-2023-072166
    OBJECTIVE: To conduct a cultural adaptation and validation of the Champion Health Belief Model Scale (CHBMS) for colorectal cancer (CRC) screening (CHBMS-CRC-M) in order to assess and investigate perceptions and beliefs about CRC screening in Malaysia.

    DESIGNS AND PARTICIPANTS: The results from an evidence synthesis and the outcomes from an expert panel discussion were used to shape CHBMS scale content into an assessment of beliefs about CRC screening (CHBMS-CRC). This questionnaire assessment was translated into the official language of Malaysia. An initial study tested the face validity of the new scale or questionnaire with 30 men and women from various ethnic groups. Factorial or structural validity was investigated in a community sample of 954 multiethnic Malaysians.

    SETTING: Selangor state, Malaysia.

    RESULTS: The new scale was culturally acceptable to the three main ethnic groups in Malaysia and achieved good face validity. Cronbach's alpha coefficients ranged from 0.66 to 0.93, indicating moderate to good internal consistency. Items relating to perceived susceptibility to CRC 'loaded' on Factor 1 (with loadings scoring above 0.90); perceived benefits of CRC screening items loaded on factor 2 and were correlated strongly (loadings ranged between 0.63 and 0.83) and perceived barriers (PBA) to CRC screening (PBA) items loaded on factor 3 (range 0.30-0.72).

    CONCLUSION: The newly developed CHBMS-CRC-M fills an important gap by providing a robust scale with which to investigate and assess CRC screening beliefs and contribute to efforts to enhance CRC screening uptake and early detection of CRC in Malaysia and in other Malay-speaking communities in the region.

  10. Ricketts CJ, Morris MR, Gentle D, Shuib S, Brown M, Clarke N, et al.
    Clin Epigenetics, 2013 Sep 13;5(1):16.
    PMID: 24034811 DOI: 10.1186/1868-7083-5-16
    BACKGROUND: Despite therapeutic advances in targeted therapy, metastatic renal cell carcinoma (RCC) remains incurable for the vast majority of patients. Key molecular events in the pathogenesis of RCC include inactivation of the VHL tumour suppressor gene (TSG), inactivation of chromosome 3p TSGs implicated in chromatin modification and remodelling and de novo tumour-specific promoter methylation of renal TSGs. In the light of these observations it can be proposed that, as in some haematological malignancies, demethylating agents such as azacitidine might be beneficial for the treatment of advanced RCC.

    RESULTS: Here we report that the treatment of RCC cell lines with azacitidine suppressed cell proliferation in all 15 lines tested. A marked response to azacitidine therapy (>50% reduction in colony formation assay) was detected in the three cell lines with VHL promoter methylation but some RCC cell lines without VHL TSG methylation also demonstrated a similar response suggesting that multiple methylated TSGs might determine the response to demethylating therapies. To identify novel candidate methylated TSGs implicated in RCC we undertook a combined analysis of copy number and CpG methylation array data. Candidate novel epigenetically inactivated TSGs were further prioritised by expression analysis of RCC cell lines pre and post-azacitidine therapy and comparative expression analysis of tumour/normal pairs. Thus, with subsequent investigation two candidate genes were found to be methylated in more than 25% of our series and in the TCGA methylation dataset for 199 RCC samples: RGS7 (25.6% and 35.2% of tumours respectively) and NEFM in (25.6% and 30.2%). In addition three candidate genes were methylated in >10% of both datasets (TMEM74 (15.4% and 14.6%), GCM2 (41.0% and 14.6%) and AEBP1 (30.8% and 13.1%)). Methylation of GCM2 (P = 0.0324), NEFM (P = 0.0024) and RGS7 (P = 0.0067) was associated with prognosis.

    CONCLUSIONS: These findings provide preclinical evidence that treatment with demethylating agents such as azacitidine might be useful for the treatment of advanced RCC and further insights into the role of epigenetic changes in the pathogenesis of RCC.

  11. Chuah KH, Black CJ, Tee V, Lim SZ, Hian WX, Sahran NF, et al.
    Aliment Pharmacol Ther, 2023 Jul;58(2):168-174.
    PMID: 37259882 DOI: 10.1111/apt.17567
    BACKGROUND: The prevalence of irritable bowel syndrome (IBS) is now known to be similar in various geographical regions, but there has been no study directly comparing characteristics of patients with IBS between populations.

    AIMS: To evaluate clinical and psychological differences between adults with IBS seen in secondary care in the United Kingdom (UK) and Malaysia.

    METHODS: Age- and sex-matched patients with IBS from a single centre in the UK (Leeds) and two centres in Malaysia (Kuala Lumpur and Kota Bharu), who fulfilled Rome III criteria, were recruited prospectively. Demographic characteristics and gastrointestinal and psychological symptoms were compared between both groups.

    RESULTS: A total of 266 (133 UK and 133 Malaysian) age- and sex-matched patients with Rome III IBS were recruited (mean age: 45.1 years Malaysia, vs. 46.5 years UK; 57.9% female). UK patients were more likely to consume alcohol than Malaysian patients (54.1% vs. 10.5%, p 

  12. Kavana N, Sonaimuthu P, Kasanga C, Kassuku A, Al-Mekhlafi HM, Fong MY, et al.
    Am J Trop Med Hyg, 2016 Oct 05;95(4):874-876.
    PMID: 27481059 DOI: 10.4269/ajtmh.16-0211
    In this study, the seroprevalence of sparganosis and its relationship with sociodemographic factors in northern Tanzania have been assessed. A total of 216 serum samples from two rural districts, Monduli and Babati, were tested for sparganosis using an enzyme-linked immunosorbent assay. The seroprevalence of anti-sparganum IgG antibodies was 62.5% (95% confidence interval [CI] = 56.1-68.9) in all age groups. There were significant associations between district (relative risk [RR] = 1.95, 95% CI = 1.42-2.69), education (RR = 1.40, 95% CI = 1.15-1.70), and pet ownership with seropositivity (RR = 1.48, 95% CI = 1.02-2.16) based on univariate analysis. However, only the district was significantly associated with seropositivity (odds ratio = 4.20, 95% CI = 1.89-9.32) in binary logistic regression analysis. Providing health education to people residing in sparganosis-endemic areas is likely to improve the efficacy of preventative measures and reduce human disease burden.
  13. Green CG, Ong MLY, Rowland SN, Bongiovanni T, James LJ, Clifford T, et al.
    Food Funct, 2024 Nov 25;15(23):11525-11536.
    PMID: 39498577 DOI: 10.1039/d4fo04028g
    Acetate, propionate, and butyrate are naturally-occurring short-chain fatty acids (SCFAs) derived from bacterial metabolism of dietary fibre and have been associated with numerous positive health outcomes. All three acids have been shown to offer unique physiological and metabolic effects and, therefore, could be targeted for co-ingestion as part of a nutritional/medicinal plan. However, a better understanding of the outcomes of supplementing in combination on circulating concentration profiles is necessary to confirm uptake efficacy. This study sought to investigate the acute circulating concentration profiles of acetate, propionate, and butyrate following oral supplementation. Three experimental trials were conducted including investigations to understand the impact of capsule coating on circulating concentration profiles, the effect of supplementation dose on uptake kinetics, and the outcome of a short, repeated, supplementation routine on circulating levels. Serum samples were analysed for SCFA content using a quantitative GC-MS assay. It was observed that an acid-resistant coated capsule caused a delayed and blunted blood concentration response, with the non-acid resistant trial displaying earlier and more intense peak serum concentrations. For dose comparison investigations, all SCFAs peaked within 60 min and returned to baseline concentrations by 120 min post-supplementation. A graded dose relationship was present for propionate and butyrate when considering the total circulating exposure across a 240 min monitoring period. In addition, a one-week, twice-daily, repeated supplementation protocol resulted in no changes in basal serum SCFA concentrations. Overall, these data indicate that acetate, propionate, and butyrate display relatively similar circulating concentration profiles following oral co-ingestion, adding knowledge to help inform supplementation strategies for future outcomes where acute elevation of circulating SCFAs is desired.
  14. Wang H, Gao C, Guignard-Duff M, Cole C, Hall C, Baruah R, et al.
    Heart, 2025 Jan 29.
    PMID: 39880470 DOI: 10.1136/heartjnl-2024-324160
    BACKGROUND: Early heart failure (HF) diagnosis is crucial to ensure that optimal guideline-directed medical therapy (GDMT) is administered to reduce morbidity and mortality. Limited access to echocardiography could lead to a later diagnosis for patients, for example, during an HF hospitalisation (hHF). This study aimed to compare the incidence and outcomes of inpatient versus outpatient diagnosis of HF.

    METHODS: Electronic health records were linked to echocardiography data between 2015 and 2021 from patients in Tayside, Scotland (population~450 000). Incident HF diagnosis was classified into inpatient or outpatient and stratified by ejection fraction (EF). A non-HF comparator group with normal left ventricular function was also defined. The primary outcome was time to cardiovascular death or hHF within 12 months of diagnosis.

    RESULTS: In total, 5223 individuals were identified, 4231 with HF (1115 heart failure with reduced ejection fraction (HFrEF), 666 heart failure with mildly reduced ejection fraction, 1402 heart failure with preserved ejection fraction and 1048 HF with unknown EF) and 992 with non-HF comparators. Of the 4231 HF patients, 2169 (51.3%) were diagnosed as inpatients. The primary outcome was observed in 1193 individuals with HF (28.1%) and 32 (3.2%) non-HF comparators and was significantly more likely to occur in individuals diagnosed as inpatients than outpatients (809 vs 384 events; adjusted HR: 1.62 (1.39-1.89), p<0.001), and this was consistent regardless of EF. For HFrEF patients first diagnosed as inpatients, those discharged on ≥2 GDMT had a reduced incidence of the primary outcome compared with those discharged on <2 GDMT (303 vs 175 events; adjusted HR: 0.72 (0.55-0.94), p=0.016).

    CONCLUSIONS: Individuals whose first presentation was a HF hospitalisation had a significantly worse outcome than those who were diagnosed in the community. Among hospitalised individuals, higher use of GDMT was associated with improved outcomes. Our results highlight the importance of improving diagnostic pathways to allow for earlier identification and treatment of HF.

  15. Zhu CZ, Samuel OD, Taheri-Garavand A, Elboughdiri N, Paramasivam P, Hussain F, et al.
    Sci Rep, 2025 Feb 15;15(1):5638.
    PMID: 39955378 DOI: 10.1038/s41598-025-88901-9
    Researchers and stakeholders have shown interest in heterogeneous composite biodiesel (HCB) due to its enhanced fuel properties and environmental friendliness (EF). The lack of high viscosity datasets for parent hybrid oils has hindered their commercialisation. Reliable models are lacking to optimise the transesterification parameters for developing HCB, and the scarcity of predictive models has affected climate researchers and environmental experts. In this study, basic fuel properties were analysed, and models were developed models for the yield of HCB and kinematic viscosity (KV) for composite biodiesel/neem castor seed oil methyl ester (NCSOME) using Artificial Neural Network (ANN) and Adaptive Neuro Fuzzy Inference System (ANFIS). Statistical indices such as computed coefficient of determination (R2), root-mean-square-error (RMSE), standard error of prediction (SEP), mean average error (MAE), and average absolute deviation (AAD) were used to evaluate the effectiveness of the techniques. Emission models for NCSOME-diesel blends were also established. The study investigated the impact of optimised fuel types/NCSOME-diesel (10-30 vol%), ZnO nanoparticle dosage (400-800 ppm), engine speed (1100-1700 rpm), and engine load (10-30%) on emission characteristics and environmental friendliness indices (EFI) such as carbon monoxide (CO), Oxides of Nitrogen (NOx), and Unburnt Hydrocarbon (UHC) using Response Surface Methodology (RSM). The ANFIS model demonstrated superior performance in terms of R2, RMSE, SEP, MAE, and AAD compared to the ANN model in predicting yield and KV of HCB. The optimal emission levels for CO (49.26 ppm), NOx (0.5171 ppm), and UHC (2.783) were achieved with a fuel type of 23.4%, nanoparticle dosage of 685.432 ppm, engine speed of 1329.2 rpm, and engine load of 10% to ensure cleaner EFI. The hybrid ANFIS and ANN models can effectively predict and model fuel-related characteristics and improve the HCB process, while the RSM model can be a valuable tool for climate and environmental stakeholders in accurate forecasting and promoting a cleaner environment. The valuable datasets can also provide reliable information for strategic planning in the biodiesel and automotive industries.
  16. Wong WJ, Nguyen TV, Ahmad F, Vu HTT, Koh AS, Tan KM, et al.
    J Clin Hypertens (Greenwich), 2025 Jan;27(1):e14936.
    PMID: 39545715 DOI: 10.1111/jch.14936
    Diabetes is one of the most pressing health issues in the Southeast Asian region, and hypertension has been commonly reported as a comorbidity in adults with diabetes. This systematic review aimed to synthesize evidence on the prevalence and management of hypertension in adults with diabetes in Southeast Asian countries. A literature search was conducted in Ovid MEDLINE and Embase Classic + Embase from database inception until March 15, 2024. Studies were included if (1) they were conducted in Southeast Asian countries, (2) the study populations were adults with diabetes, and (3) there was information related to hypertension or blood pressure (BP) in the study results. Of the 7486 abstracts found, 90 studies qualified for this review. Most studies reported a hypertension prevalence of 70% or higher (ranging from 29.4% to 93.4%). Despite this high prevalence, a substantial proportion of these populations did not receive adequate BP control, with most studies indicating a control rate of less than 40%. There was limited evidence on the prescription of antihypertensive therapies and medication adherence. There was a lack of studies from 4 of the 11 countries in the region. This review highlights that BP control in adults with diabetes remains a significant challenge in Southeast Asia. Given the ongoing epidemiological transition, and the increasing older population in this region who are likely to accumulate multiple chronic conditions complicating medication strategies, this review highlights the urgent need to improve BP management in those with diabetes.
  17. Mulenga M, Rajamanikam A, Kumar S, Muhammad SB, Bhassu S, Samudid C, et al.
    PLoS One, 2025;20(1):e0316493.
    PMID: 39879257 DOI: 10.1371/journal.pone.0316493
    The emergence of Next Generation Sequencing (NGS) technology has catalyzed a paradigm shift in clinical diagnostics and personalized medicine, enabling unprecedented access to high-throughput microbiome data. However, the inherent high dimensionality, noise, and variability of microbiome data present substantial obstacles to conventional statistical methods and machine learning techniques. Even the promising deep learning (DL) methods are not immune to these challenges. This paper introduces a novel feature engineering method that circumvents these limitations by amalgamating two feature sets derived from input data to generate a new dataset, which is then subjected to feature selection. This innovative approach markedly enhances the Area Under the Curve (AUC) performance of the Deep Neural Network (DNN) algorithm in colorectal cancer (CRC) detection using gut microbiome data, elevating it from 0.800 to 0.923. The proposed method constitutes a significant advancement in the field, providing a robust solution to the intricacies of microbiome data analysis and amplifying the potential of DL methods in disease detection.
  18. Song HS, Ahamed F, Lee JY, Henry CS, Edirisinghe JN, Nelson WC, et al.
    Sci Rep, 2025 Feb 19;15(1):6042.
    PMID: 39972043 DOI: 10.1038/s41598-025-89997-9
    Integrating genome-scale metabolic networks with reactive transport models (RTMs) provides a detailed description of the dynamic changes in microbial growth and metabolism. Despite promising demonstrations in the past, computational inefficiency has been pointed out as a critical issue to overcome because it requires repeated application of linear programming (LP) to obtain flux balance analysis (FBA) solutions in every time step and spatial grid. To address this challenge, we propose a new simulation method where we train and validate artificial neural networks (ANNs) using randomly sampled FBA solutions and incorporate the resulting surrogate FBA model (represented as algebraic equations) into RTMs as source/sink terms. We demonstrate the efficiency of our method via a case study of Shewanella oneidensis MR-1. During aerobic growth on lactate, S. oneidensis produces metabolic byproducts (such as pyruvate and acetate), which are subsequently consumed as alternative carbon sources when the preferred nutrients are depleted. To effectively simulate these complex dynamics, we used a cybernetic approach that models metabolic switches as the outcome of dynamic competition among multiple growth options. In both zero-dimensional batch and one-dimensional column configurations, the ANN-based surrogate models achieved substantial reduction of computational time by several orders of magnitude compared to the original LP-based FBA models. Moreover, the ANN models produced robust solutions without any special measures to prevent numerical instability. These developments significantly promote our ability to utilize genome-scale networks in complex, multi-physics, and multi-dimensional ecosystem modeling.
  19. Koh CMM, Hwang SS, Lau BT, Palombo EA, Ginjom IRH, Ha CHX, et al.
    ACS Infect Dis, 2025 Feb 14;11(2):413-429.
    PMID: 39423324 DOI: 10.1021/acsinfecdis.4c00549
    Pseudomonas aeruginosa is the predominant bacterium found in many chronic biofilm infections. Over the past few decades, biofilm-related infections have posed a significant challenge to medical practice due to the increasing emergence of multidrug resistance. Cis-2-decenoic acid (CDA), a small molecule found in P. aeruginosa, has been shown to disperse biofilms formed by various bacteria and to work in synergy with common antibiotics. Despite that, the binding mechanism between CDA and the predicted cyclases/histidine kinases associated sensory extracellular (CHASE) domain of sensor protein DspS remains unknown in the absence of a crystallized protein structure. Moreover, the therapeutic potential of CDA is limited by its susceptibility to oxidative degradation and isomerization. In this work, we propose a structural model for the DspS CHASE domain. The resulting model displays an overall topology reminiscent of the sensor protein PcrK in Xanthomonas campestris. Through molecular dynamics simulations, a stable potential binding site for CDA was further identified. Virtual screening against the predicted site of DspS CHASE using our developed pipeline discovered two promising compounds, compounds 2 and 9, capable of dislodging 7-day P. aeruginosa biofilms at 50 μM without affecting bacterial growth. These compounds also enhanced the effects of ciprofloxacin against P. aeruginosa, reduced the survival of dispersed cells, and increased the expression of matrix-degrading enzyme genes pelA, pslG, and eddA. This study provides insights into CDA recognition by DspS and represents the first large-scale effort to uncover first-in-class DspS activators. At the same time, this work also underscores the effectiveness of a computational-aided drug discovery process in finding new activators, even without a known protein structure.
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