Browse publications by year: 2023

  1. Chen C, Yi R, Igisu M, Sakaguchi C, Afrin R, Potiszil C, et al.
    Small Methods, 2023 Dec;7(12):e2300119.
    PMID: 37203261 DOI: 10.1002/smtd.202300119
    α-Hydroxy acids are prebiotic monomers that undergo dehydration synthesis to form polyester gels, which assemble into membraneless microdroplets upon aqueous rehydration. These microdroplets are proposed as protocells that can segregate and compartmentalize primitive molecules/reactions. Different primitive aqueous environments with a variety of salts could have hosted chemistries that formed polyester microdroplets. These salts could be essential cofactors of compartmentalized prebiotic reactions or even directly affect protocell structure. However, fully understanding polyester-salt interactions remains elusive, partially due to technical challenges of quantitative measurements in condensed phases. Here, spectroscopic and biophysical methods are applied to analyze salt uptake by polyester microdroplets. Inductively coupled plasma mass spectrometry is applied to measure the cation concentration within polyester microdroplets after addition of chloride salts. Combined with methods to determine the effects of salt uptake on droplet turbidity, size, surface potential and internal water distribution, it was observed that polyester microdroplets can selectively partition salt cations, leading to differential microdroplet coalescence due to ionic screening effects reducing electrostatic repulsion forces between microdroplets. Through applying existing techniques to novel analyses related to primitive compartment chemistry and biophysics, this study suggests that even minor differences in analyte uptake can lead to significant protocellular structural change.
  2. Hoo JX, Yang YF, Tan JY, Yang J, Yang A, Lim LL
    Eur Heart J Qual Care Clin Outcomes, 2023 Apr 26;9(3):258-267.
    PMID: 35687013 DOI: 10.1093/ehjqcco/qcac032
    AIMS: Multicomponent integrated care is associated with sustained control of multiple cardiometabolic risk factors among patients with type 2 diabetes. There is a lack of data in patients with acute coronary syndrome (ACS). We aimed to examine its efficacy on mortality and hospitalization outcomes among patients with ACS in outpatient settings.

    METHODS AND RESULTS: A literature search was conducted on PubMed, EMBASE, Ovid, and Cochrane library databases for randomized controlled trials, published in English language between January 1980 and November 2020. Multicomponent integrated care defined as two or more quality improvement strategies targeting different domains (the healthcare system, healthcare providers, and patients) for one month or more. The study outcomes were all-cause and cardiovascular-related mortality, hospitalization, and emergency department visits. We pooled the risk ratio (RR) with 95% confidence interval (CI) for the association between multicomponent integrated care and study outcomes using the Mantel-Haenszel test. 74 trials (n = 93 278 patients with ACS) were eligible. The most common quality improvement strategies were team change (83.8%), patient education (62.2%), and facilitated patient-provider relay (54.1%). Compared with usual care, multicomponent integrated care was associated with reduced risks for all-cause mortality (RR 0.83, 95% CI 0.77-0.90; P 

    MeSH terms: Diabetes Mellitus, Type 2*; Hospitalization; Humans; Delivery of Health Care, Integrated*
  3. Patel VK, Shirbhate E, Tiwari P, Kore R, Veerasamy R, Mishra A, et al.
    Curr Med Chem, 2023;30(24):2762-2795.
    PMID: 36154583 DOI: 10.2174/0929867329666220922105615
    Multi-targeted agents can interact with multiple targets sequentially, resulting in synergistic and more effective therapies for several complicated disorders, including cancer, even with relatively modest activity. Histone deacetylase (HDAC) inhibitors are low molecular weight small compounds that increase the acetylation of histone and nonhistone proteins, altering gene expression and thereby impacting angiogenesis, metastasis, and apoptosis, among other processes. The HDAC inhibitors affect multiple cellular pathways thus producing adverse issues, causing therapeutic resistance, and they have poor pharmacokinetic properties. The designing of HDAC-based dual/multi-target inhibitor is an important strategy to overcome adverse effects, drug resistance and increase the effectiveness in controlling cancer. The selection of target combinations to design multitarget HDAC inhibitor is generally accomplished on the basis of systematic highthroughput screening (HTS), network pharmacology analysis methods. The identification of the pharmacophore against individual targets is performed using rational or computation methods. The identified pharmacophore can combine with merged, fused, or linked with the cleavable or non-cleavable linker to retain the interaction with the original target while being compatible with the other target. The objective of this review is to elucidate the potential targets' design strategies, biological activity, and the recent development of dual/multi-targeting HDAC inhibitors as potential anticancer agents. This review elucidates the designing strategies of the potential target along with biological activity and the recent development of dual/multi-targeting HDAC inhibitors as potential anticancer agents. The development of HDAC-based dual/multi-target inhibitors is important for overcoming side effects, drug resistance, and effective cancer control.
    MeSH terms: Histone Deacetylase Inhibitors/pharmacology; Histone Deacetylase Inhibitors/therapeutic use
  4. Krishnan K, Law ZK, Woodhouse LJ, Dineen RA, Sprigg N, Wardlaw JM, et al.
    Stroke Vasc Neurol, 2023 Apr;8(2):151-160.
    PMID: 36202546 DOI: 10.1136/svn-2021-001375
    BACKGROUND AND PURPOSE: Intracerebral haemorrhage volume (ICHV) is prognostically important but does not account for intracranial volume (ICV) and cerebral parenchymal volume (CPV). We assessed measures of intracranial compartments in acute ICH using computerised tomography scans and whether ICHV/ICV and ICHV/CPV predict functional outcomes. We also assessed if cistern effacement, midline shift, old infarcts, leukoaraiosis and brain atrophy were associated with outcomes.

    METHODS: Data from 133 participants from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial trial were analysed. Measures included ICHV (using ABC/2) and ICV (XYZ/2) (by independent observers); ICHV, ICV and CPV (semiautomated segmentation, SAS); atrophy (intercaudate distance, ICD, Sylvian fissure ratio, SFR); midline shift; leukoaraiosis and cistern effacement (visual assessment). The effects of these measures on death at day 4 and poor functional outcome at day 90 (modified Rankin scale, mRS of >3) was assessed.

    RESULTS: ICV was significantly different between XYZ and SAS: mean (SD) of 1357 (219) vs 1420 (196), mean difference (MD) 62 mL (p<0.001). There was no significant difference in ICHV between ABC/2 and SAS. There was very good agreement for ICV measured by SAS, CPV, ICD, SFR, leukoaraiosis and cistern score (all interclass correlations, n=10: interobserver 0.72-0.99, intraobserver 0.73-1.00). ICHV/ICV and ICHV/CPV were significantly associated with mRS at day 90, death at day 4 and acute neurological deterioration (all p<0.05), similar to ICHV. Midline shift and cistern effacement at baseline were associated with poor functional outcome but old infarcts, leukoaraiosis and brain atrophy were not.

    CONCLUSIONS: Intracranial compartment measures and visual estimates are reproducible. ICHV adjusted for ICH and CPV could be useful to prognosticate in acute stroke. The presence of midline shift and cistern effacement may predict outcome but the mechanisms need validation in larger studies.

    MeSH terms: Atrophy/complications; Cerebral Hemorrhage/complications; Cerebral Hemorrhage/drug therapy; Nitroglycerin/adverse effects; Humans; Stroke*
  5. Liew A, Lee CC, Subramaniam V, Lan BL, Tan M
    J Magn Reson Imaging, 2023 Jun;57(6):1728-1740.
    PMID: 36208095 DOI: 10.1002/jmri.28456
    BACKGROUND: Research suggests that treatment of multiple brain metastases (BMs) with stereotactic radiosurgery shows improvement when metastases are detected early, providing a case for BM detection capabilities on small lesions.

    PURPOSE: To demonstrate automatic detection of BM on three MRI datasets using a deep learning-based approach. To improve the performance of the network is iteratively co-trained with datasets from different domains. A systematic approach is proposed to prevent catastrophic forgetting during co-training.

    STUDY TYPE: Retrospective.

    POPULATION: A total of 156 patients (105 ground truth and 51 pseudo labels) with 1502 BM (BrainMetShare); 121 patients with 722 BM (local); 400 patients with 447 primary gliomas (BrATS). Training/pseudo labels/validation data were distributed 84/51/21 (BrainMetShare). Training/validation data were split: 121/23 (local) and 375/25 (BrATS).

    FIELD STRENGTH/SEQUENCE: A 5 T and 3 T/T1 spin-echo postcontrast (T1-gradient echo) (BrainMetShare), 3 T/T1 magnetization prepared rapid acquisition gradient echo postcontrast (T1-MPRAGE) (local), 0.5 T, 1 T, and 1.16 T/T1-weighted-fluid-attenuated inversion recovery (T1-FLAIR) (BrATS).

    ASSESSMENT: The ground truth was manually segmented by two (BrainMetShare) and four (BrATS) radiologists and manually annotated by one (local) radiologist. Confidence and volume based domain adaptation (CAVEAT) method of co-training the three datasets on a 3D nonlocal convolutional neural network (CNN) architecture was implemented to detect BM.

    STATISTICAL TESTS: The performance was evaluated using sensitivity and false positive rates per patient (FP/patient) and free receiver operating characteristic (FROC) analysis at seven predefined (1/8, 1/4, 1/2, 1, 2, 4, and 8) FPs per scan.

    RESULTS: The sensitivity and FP/patient from a held-out set registered 0.811 at 2.952 FP/patient (BrainMetShare), 0.74 at 3.130 (local), and 0.723 at 2.240 (BrATS) using the CAVEAT approach with lesions as small as 1 mm being detected.

    DATA CONCLUSION: Improved sensitivities at lower FP can be achieved by co-training datasets via the CAVEAT paradigm to address the problem of data sparsity.

    LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

    MeSH terms: Humans; Magnetic Resonance Imaging/methods; Retrospective Studies; Neural Networks (Computer)
  6. Mahalingam G, Samtani S, Lam BCP, Lipnicki DM, Lima-Costa MF, Blay SL, et al.
    Alzheimers Dement, 2023 Nov;19(11):5114-5128.
    PMID: 37102417 DOI: 10.1002/alz.13072
    INTRODUCTION: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers.

    METHODS: We used individual participant data (N = 39271, Mage  = 70.67 (40-102), 58.86% female, Meducation  = 8.43 years, Mfollow-up  = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes.

    RESULTS: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.

    DISCUSSION: Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally.

    HIGHLIGHTS: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.

    MeSH terms: Aged; Aging/psychology; Female; Humans; Longitudinal Studies; Male; Cohort Studies
  7. Bashiri Z, Moghaddaszadeh A, Falak R, Khadivi F, Afzali A, Abbasi M, et al.
    Macromol Biosci, 2023 Sep;23(9):e2200574.
    PMID: 37116215 DOI: 10.1002/mabi.202200574
    In vitro production of sperm is a desirable idea for fertility preservation in azoospermic men and prepubertal boys suffering from cancer. In this study, a biocompatible porous scaffold based on a triad mixture of silk fibroin (SF), alginate (Alg), and laminin (LM) is developed to facilitate the differentiation of mouse spermatogonia stem cells (SSCs). Following SF extraction, the content is analyzed by SDS-PAGE and stable porous 3D scaffolds are successfully prepared by merely Alg, SF, and a combination of Alg-SF, or Alg-SF-LM through freeze-drying. Then, the biomimetic scaffolds are characterized regarding the structural and biological properties, water absorption capacity, biocompatibility, biodegradability, and mechanical behavior. Neonatal mice testicular cells are seeded on three-dimensional scaffolds and their differentiation efficiency is evaluated using real-time PCR, flow cytometry, immunohistochemistry. Blend matrices showed uniform porous microstructures with interconnected networks, which maintained long-term stability and mechanical properties better than homogenous structures. Molecular analysis of the cells after 21 days of culture showed that the expression of differentiation-related proteins in cells that are developed in composite scaffolds is significantly higher than in other groups. The application of a composite system can lead to the differentiation of SSCs, paving the way for a novel infertility treatment landscape in the future.
    MeSH terms: Alginates; Animals; Haploidy; Laminin; Male; Semen/metabolism; Spermatids/metabolism; Porosity; Tissue Engineering/methods; Silk/chemistry; Mice; Tissue Scaffolds/chemistry
  8. Swami V, Voracek M, Furnham A, Robinson C, Tran US
    Body Image, 2023 Jun;45:391-400.
    PMID: 37116305 DOI: 10.1016/j.bodyim.2023.04.005
    In the present study, we sought to position support for weight-related anti-discrimination laws and policies within a broader political and socioeconomic context. Specifically, we hypothesised that individualistic (rather than structural) anti-poverty attitudes would provide the basis for negative weight-related dispositions. To test this hypothesis, we asked 392 respondents from the United Kingdom to complete measures of support for weight-related anti-discrimination laws and policies, attributions about the causes of being larger-bodied, and weight-related stigma and prejudice. Path analysis with robust maximum likelihood estimation indicated that greater individualistic anti-poverty attitudes were significantly and directly associated with lower support for weight-related anti-discrimination laws and policies. This direct association was also significantly mediated by weight-related stigma and via a serial mediation involving both weight-related stigma and prejudice. Although greater individualistic anti-poverty attitudes were significantly associated with greater personal attributions for being larger-bodied, the latter did not emerge as a significant mediation pathway. The present findings highlight the importance of considering broader political and socioeconomic contextual factors that may provide a basis for the development, maintenance, and manifestation of negative weight-related dispositions.
    MeSH terms: Attitude; Body Image/psychology; Humans; Prejudice; Social Stigma; Policy
  9. Usman J, Salami BA, Gbadamosi A, Adamu H, Usman AG, Benaafi M, et al.
    Chemosphere, 2023 Aug;331:138726.
    PMID: 37116721 DOI: 10.1016/j.chemosphere.2023.138726
    Due to the significant energy and economic losses brought on by the global oil spill, there has been an increased interest in oil-water separation. This study presents strong non-linear machine learning models (support vector regression (SVR) and Gaussian process regression (GPR)) with the Response surface method (RSM) to predict the oil flux and oil-water separation efficiency of wastewater using ceramic membrane technology. For the model development and prediction of oil flux (OF) and oil-water separation efficiency (OSE), oil concentration (mg/L), feed flow rate (mL/min), and pH were considered as input variables. The input variables are combined in three combinations to study the most contributing input features to the models' performance. Mean square error (MSE) and Nash-Sutcliffe coefficient efficiency (NSE) were used to assess the prediction performances of the developed models with the different number of input combinations considered in the study. For the two target variables (OF and OSE), GPR and SVR models were used to separately predict them. For OF, the SVR-2 [Combo-2] model (MSE = 0.9255 and NSE = 2.7976) performed better with higher prediction accuracy compared to GPR-2 [Combo-2] model (MSE = 0.763 and NSE = 6.437). In addition, for OSE, the GPR-3 [Combo-3] model (MSE = 0.995 and NSE = 0.5544) performed slightly better than SVR-3 [Combo-3] model (MSE = 0.992 and NSE = 0.8066). The results showed that the SVR model with the combo-2 and GPR-3 models for OF and OSE variables are the proposed models with the best performance and accuracy. This machine learning study will aid in better evaluating the function of materials such as ceramic in membrane performance features such as oil flux and rejection prediction, separation efficiency, water recovery, membrane fouling, and so on. As for academics and manufacturers, this machine learning (ML) strategy will boost performance and allow a better understanding of system governance.
    MeSH terms: Ceramics; Water; Hydrophobic and Hydrophilic Interactions; Waste Water*
  10. Kaplan E, Baygin M, Barua PD, Dogan S, Tuncer T, Altunisik E, et al.
    Med Eng Phys, 2023 May;115:103971.
    PMID: 37120169 DOI: 10.1016/j.medengphy.2023.103971
    PURPOSE: The classification of medical images is an important priority for clinical research and helps to improve the diagnosis of various disorders. This work aims to classify the neuroradiological features of patients with Alzheimer's disease (AD) using an automatic hand-modeled method with high accuracy.

    MATERIALS AND METHOD: This work uses two (private and public) datasets. The private dataset consists of 3807 magnetic resonance imaging (MRI) and computer tomography (CT) images belonging to two (normal and AD) classes. The second public (Kaggle AD) dataset contains 6400 MR images. The presented classification model comprises three fundamental phases: feature extraction using an exemplar hybrid feature extractor, neighborhood component analysis-based feature selection, and classification utilizing eight different classifiers. The novelty of this model is feature extraction. Vision transformers inspire this phase, and hence 16 exemplars are generated. Histogram-oriented gradients (HOG), local binary pattern (LBP) and local phase quantization (LPQ) feature extraction functions have been applied to each exemplar/patch and raw brain image. Finally, the created features are merged, and the best features are selected using neighborhood component analysis (NCA). These features are fed to eight classifiers to obtain highest classification performance using our proposed method. The presented image classification model uses exemplar histogram-based features; hence, it is called ExHiF.

    RESULTS: We have developed the ExHiF model with a ten-fold cross-validation strategy using two (private and public) datasets with shallow classifiers. We have obtained 100% classification accuracy using cubic support vector machine (CSVM) and fine k nearest neighbor (FkNN) classifiers for both datasets.

    CONCLUSIONS: Our developed model is ready to be validated with more datasets and has the potential to be employed in mental hospitals to assist neurologists in confirming their manual screening of AD using MRI/CT images.

    MeSH terms: Humans; Image Interpretation, Computer-Assisted/methods; Magnetic Resonance Imaging/methods; Tomography, X-Ray Computed
  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.
    MeSH terms: Animals; Humans; Indonesia; Malaysia; Mammals; Reoviridae Infections*
  12. 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.

    MeSH terms: Agriculture; Communicable Disease Control; Humans; Malaysia/epidemiology
  13. Federspiel F, Mitchell R, Asokan A, Umana C, McCoy D
    BMJ Glob Health, 2023 May;8(5).
    PMID: 37160371 DOI: 10.1136/bmjgh-2022-010435
    While artificial intelligence (AI) offers promising solutions in healthcare, it also poses a number of threats to human health and well-being via social, political, economic and security-related determinants of health. We describe three such main ways misused narrow AI serves as a threat to human health: through increasing opportunities for control and manipulation of people; enhancing and dehumanising lethal weapon capacity and by rendering human labour increasingly obsolescent. We then examine self-improving 'artificial general intelligence' (AGI) and how this could pose an existential threat to humanity itself. Finally, we discuss the critical need for effective regulation, including the prohibition of certain types and applications of AI, and echo calls for a moratorium on the development of self-improving AGI. We ask the medical and public health community to engage in evidence-based advocacy for safe AI, rooted in the precautionary principle.
    MeSH terms: Artificial Intelligence*; Female; Humans; Labor, Obstetric*; Pregnancy; Public Health
  14. Chen H
    Environ Sci Pollut Res Int, 2023 Jun;30(29):73361-73371.
    PMID: 37184784 DOI: 10.1007/s11356-023-27520-1
    Carbon emission trading is an important environmental policy tool to promote carbon emission reduction. With the panel data of carbon emissions trading (CET) pilots, this paper used the spatial difference-in-difference model (SDID) to test whether CET can affect the enterprise environmental responsibility and the spatial spillover effect of carbon emissions trading. The study found that CET can significantly improve the environmental responsibility level of enterprises in pilot areas. The environmental responsibility level of enterprises in surrounding areas are also improved driven by CET. In the time dimension, the role of CET in improving the enterprise environmental responsibility is gradually increasing. The impact of CET on enterprise environmental responsibility has significant heterogeneity in the dimension of ownership attributes and environmental regulation. Promoting corporate environmental protection investment is the main path for CET to improve the enterprise environmental responsibility.
    MeSH terms: Carbon*; China; Investments; Ownership; Environmental Policy*
  15. Chan EEH, Merchant K, Othman MY, Laksmi NK
    BMJ Case Rep, 2023 Apr 25;16(4).
    PMID: 37185243 DOI: 10.1136/bcr-2022-252484
    Hirschsprung's disease (HD) is one of the most well-known gastrointestinal motility disorders. Diagnosis and management of other lesser-known motility disorders are often challenging and tedious. We describe a teenager who was severely constipated from birth and needed intensive care admissions for life-threatening enterocolitis. She also had concomitant anal stenosis. Several rectal biopsies were unable to yield a conclusive diagnosis. Surgical level of resection had to be identified based on the motility of the bowel as determined by transit studies using oral ingestion of a milk feed labelled with Technetium-99m colloid. After completion of all operative stages, histopathological examination of the excised specimens concluded that she had short-segment HD associated with reduced interstitial cells of Cajal in the large bowel. She is currently continent, evacuating voluntarily approximately four times a day and is relieved of all her symptoms.
    MeSH terms: Adolescent; Constriction, Pathologic; Female; Humans; Intestine, Large; Intestines; Anorectal Malformations*
  16. Kamal A, Kanchau JD, Shahuri NS, Mohamed-Yassin MS, Baharudin N, Abdul Razak S, et al.
    Am J Case Rep, 2023 Apr 27;24:e939489.
    PMID: 37185657 DOI: 10.12659/AJCR.939489
    BACKGROUND In Malaysia, the prevalence of genetically confirmed heterozygous familial hypercholesterolemia (FH) was reported as 1 in 427. Despite this, FH remains largely underdiagnosed and undertreated in primary care. CASE REPORT In this case series, we report 3 FH cases detected in primary care due to mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein-B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. The mutations in case 1 (frameshift c.660del pathogenic variant in LDLR gene) and case 2 (missense c.10579C>T pathogenic variant in APOB gene) were confirmed as pathogenic, while the mutation in case 3 (missense c.277C>T mutation in PCSK9 gene) may have been benign. In case 1, the patient had the highest LDL-c level, 8.6 mmol/L, and prominent tendon xanthomas. In case 2, the patient had an LDL-c level of 5.7 mmol/L and premature corneal arcus. In case 3, the patient had an LDL-c level of 5.4 mmol/L but had neither of the classical physical findings. Genetic counseling and diagnosis were delivered by primary care physicians. These index cases were initially managed in primary care with statins and therapeutic lifestyle modifications. They were referred to the lipid specialists for up-titration of lipid lowering medications. First-degree relatives were identified and referred for cascade testing. CONCLUSIONS This case series highlights different phenotypical expressions in patients with 3 different FH genetic mutations. Primary care physicians should play a pivotal role in the detection of FH index cases, genetic testing, management, and cascade screening of family members, in partnership with lipid specialists.
    MeSH terms: Apolipoproteins B/genetics; Apolipoproteins B/therapeutic use; Humans; Cholesterol, LDL/genetics; Cholesterol, LDL/therapeutic use; Mutation; Phenotype; Primary Health Care
  17. Kumarasamy G, Ismail MN, Tuan Sharif SE, Desire C, Mittal P, Hoffmann P, et al.
    Curr Issues Mol Biol, 2023 Apr 20;45(4):3603-3627.
    PMID: 37185759 DOI: 10.3390/cimb45040235
    Nearly 90% of cervical cancers are linked to human papillomavirus (HPV). Uncovering the protein signatures in each histological phase of cervical oncogenesis provides a path to biomarker discovery. The proteomes extracted from formalin-fixed paraffin-embedded tissues of the normal cervix, HPV16/18-associated squamous intraepithelial lesion (SIL), and squamous cell carcinoma (SCC) were compared using liquid chromatography-mass spectrometry (LC-MS). A total of 3597 proteins were identified, with 589, 550, and 1570 proteins unique to the normal cervix, SIL, and SCC groups, respectively, while 332 proteins overlapped between the three groups. In the transition from normal cervix to SIL, all 39 differentially expressed proteins were downregulated, while all 51 proteins discovered were upregulated in SIL to SCC. The binding process was the top molecular function, while chromatin silencing in the SIL vs. normal group, and nucleosome assembly in SCC vs. SIL groups was the top biological process. The PI3 kinase pathway appears crucial in initiating neoplastic transformation, while viral carcinogenesis and necroptosis are important for cell proliferation, migration, and metastasis in cervical cancer development. Annexin A2 and cornulin were selected for validation based on LC-MS results. The former was downregulated in the SIL vs. normal cervix and upregulated in the progression from SIL to SCC. In contrast, cornulin exhibited the highest expression in the normal cervix and lowest in SCC. Although other proteins, such as histones, collagen, and vimentin, were differentially expressed, their ubiquitous expression in most cells precluded further analysis. Immunohistochemical analysis of tissue microarrays found no significant difference in Annexin A2 expression between the groups. Conversely, cornulin exhibited the strongest expression in the normal cervix and lowest in SCC, supporting its role as a tumor suppressor and potential biomarker for disease progression.
  18. Abuhassna H, Alnawajha S
    Eur J Investig Health Psychol Educ, 2023 Mar 30;13(4):715-735.
    PMID: 37185907 DOI: 10.3390/ejihpe13040054
    Educators and course designers may face great hurdles when designing courses if they include an online setting. Instructional design (ID) has played a vital role as a change agent in facilitating the pedagogical and technological transformation of educators and students. However, some instructors still find ID challenging and there are information gaps regarding instructional design models, categories, educational context, and recommendations for future work. This systematic literature review (SLR) analyzed 31 publications using PRISMA to address this gap. The results of this review suggest combining ID models with broader theoretical frameworks. Investigations and research on ID should include a bigger number of ID types. It is highly recommended that extra frameworks be added to the ID procedure. To explore and grasp all parties engaged in ID, including the role of the instructor, the ID designer, and the student, it is important for additional educational contexts to be amalgamated. For novices in the field, such as graduate students, it is crucial to pay close attention to the several phases and techniques of ID. This review sheds light on the trends, future agenda, and research requirements associated with ID in educational settings. It might serve as a basis for future research on ID in educational contexts.
  19. Loo CY, Lee WH, Zhou QT
    Pharm Res, 2023 May;40(5):1015-1036.
    PMID: 37186073 DOI: 10.1007/s11095-023-03520-1
    With the rapid outbreak of respiratory viral infections, various biological (e.g. vaccines, peptides, recombinant proteins, antibodies and genes) and antiviral agents (e.g. ribavirin, palivizumab and valaciclovir) have been successfully developed for the treatment of respiratory virus infections such as influenza, respiratory syncytial virus and SARS-CoV-2 infections. These therapeutics are conventionally delivered via oral, intramuscular or injection route and are associated with several adverse events due to systemic toxicity. The inherent in vivo instability of biological therapeutics may hinder them from being administered without proper formulations. Therefore, we have witnessed a boom in nanotechnology coupled with a needle-free administration approach such as the inhalation route for the delivery of complex therapeutics to treat respiratory infections. This review discussed the recent advances in the inhalation strategies of nanoformulations that target virus respiratory infections.
    MeSH terms: Antiviral Agents/therapeutic use; Humans; Respiratory Syncytial Virus, Human*
  20. Ahmad Pouzi NA, Shaharir SS, Mohd Tamil A, Mustafar R, Ahmad Maulana S, Mageswaren E, et al.
    PLoS One, 2023;18(5):e0285461.
    PMID: 37186611 DOI: 10.1371/journal.pone.0285461
    OBJECTIVES: To assess the reliability and validity of two disease-specific questionnaires that assess the quality of life (QoL) among patients with Systemic Lupus Erythematosus (SLE); SLEQoL and LupusQoL in Malay language. This study also identified the factors affecting each domain of the questionnaires.

    METHODS: This cross-sectional study was conducted from June 2021 until April 2022, and SLE patients were recruited to complete the SLEQoL, LupusQoL and Short Form Health Survey (SF-36) in Malay language. Disease activity were recorded using the modified SLE Disease Activity Index (M- SLEDAI) and British Isles Lupus Assessment Group 2004 (BILAG-2004) index. Presence of organ damage was determined using the SLICC Damage index. Cronbach's alpha was calculated to determine internal consistency while exploratory factor analysis was done to determine the construct validity. Concurrent validity was evaluated using correlation with SF-36. Multiple linear regression analysis was deployed to determine the factors affecting each domain of SLEQoL and LupusQoL.

    RESULTS: A total of 125 subjects were recruited. The Cronbach's α value for the Malay-SLEQoL (M-SLEQoL) and Malay-LupusQOL (M-LupusQoL) was 0.890 and 0.944 respectively. Exploratory factor analysis found formation of similar number of components with the original version of questionnaires and all items have good factor loading of >0.4. Both instruments also had good concurrent validity with SF-36. M-SLEQoL had good correlations with BILAG-2004 and M-SLEDAI scores. Musculoskeletal (MSK) involvement was independently associated with lower M-SLEQoL in physical function, activity and symptom domains. Meanwhile, MSK and NPSLE were associated with fatigue in M-LupusQoL.

    CONCLUSION: Both M-SLEQoL and M-LupusQoL are reliable and valid as disease -specific QoL instruments for Malaysian patients. The M-Lupus QoL has better discriminative validity compared to the M-SLEQoL. SLE patients with MSK involvement are at risk of poor QoL in multiple domains including physical function, activity, symptoms and fatigue.

    MeSH terms: Cross-Sectional Studies; Fatigue/complications; Humans; Language; Malaysia; Quality of Life*; Surveys and Questionnaires; Severity of Illness Index; Reproducibility of Results
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