Browse publications by year: 2025

  1. Haysom-McDowell A, Paudel KR, Yeung S, Kokkinis S, El Sherkawi T, Chellappan DK, et al.
    Mol Oncol, 2025 Jan;19(1):15-36.
    PMID: 39592417 DOI: 10.1002/1878-0261.13764
    Lung cancer is the leading cause of cancer death globally, with non-small cell lung cancer accounting for the majority (85%) of cases. Standard treatments including chemotherapy and radiotherapy present multiple adverse effects. Medicinal plants, used for centuries, are traditionally processed by methods such as boiling and oral ingestion, However, water solubility, absorption, and hepatic metabolism reduce phytoceutical bioavailability. More recently, isolated molecular compounds from these plants can be extracted with these phytoceuticals administered either individually or as an adjunct with standard therapy. Phytoceuticals have been shown to alleviate symptoms, may reduce dosage of chemotherapy and, in some cases, enhance pharmaceutical mechanisms. Research has identified many phytoceuticals' actions on cancer-associated pathways, such as oncogenesis, the tumour microenvironment, tumour cell proliferation, metastasis, and apoptosis. The development of novel nanoparticle delivery systems such as solid lipid nanoparticles, liquid crystalline nanoparticles, and liposomes has enhanced the bioavailability and targeted delivery of pharmaceuticals and phytoceuticals. This review explores the biological pathways associated with non-small cell lung cancer, a diverse range of phytoceuticals, the cancer pathways they act upon, and the pros and cons of several nanoparticle delivery systems.
    MeSH terms: Animals; Antineoplastic Agents, Phytogenic/administration & dosage; Antineoplastic Agents, Phytogenic/pharmacology; Antineoplastic Agents, Phytogenic/therapeutic use; Antineoplastic Agents, Phytogenic/chemistry; Humans; Drug Delivery Systems; Nanoparticles/chemistry; Phytochemicals/pharmacology; Phytochemicals/therapeutic use; Phytochemicals/chemistry
  2. Retnosari R, Abdul Ghani MA, Majed Alkharji M, Wan Nawi WNIS, Ahmad Rushdan AS, Mahadi MK, et al.
    Cardiovasc Toxicol, 2025 Feb;25(2):167-181.
    PMID: 39592525 DOI: 10.1007/s12012-024-09940-8
    Doxorubicin (DOX) is a remarkable chemotherapeutic agent, however, its adverse effect on DOX-induced cardiotoxicity (DIC) is a rising concern. Recent research has identified carvacrol (CAR), an antioxidant and anti-inflammatory agent, as a promising natural compound for protecting against DIC. This study aims to investigate the potential cardioprotective effects properties of CAR in vitro and in vivo. The cardioprotective effect of CAR was assessed by pretreating H9c2 cells with non-toxic CAR for 24 h, followed by co-treatment with DOX (10 μM) for an additional 24 h. The cell viability was determined using an MTT assay. For the in vivo study, male Sprague-Dawley rats (200-250 g) were randomly divided into three groups: control, cardiotoxicity (DOX), and treatment (CAR + DOX) groups. CAR (50 mg/kg, BW) was administered orally to the CAR + DOX groups for 14 days. Then, a single dose of DOX (15 mg/kg/i.p, BW) was administered on day 15 for DOX and CAR + DOX groups. The rats were allowed to recover for 3 days before being sacrificed. Our results demonstrated that DOX (10 µM) significantly reduced H9c2 cell viability by 50% (p 
    MeSH terms: Animals; Antioxidants/pharmacology; Cell Line; Disease Models, Animal; Fibrosis; Heart Diseases/chemically induced; Heart Diseases/metabolism; Heart Diseases/pathology; Heart Diseases/physiopathology; Heart Diseases/prevention & control; Male; Ventricular Function, Left/drug effects; Rats, Sprague-Dawley*; Cytoprotection; Monoterpenes/pharmacology; Rats; Cardiotoxicity*
  3. Khandwala K, Farooqi J, Ali R, Bakhshi SK, Anwar SSM
    Neuroradiology, 2025 Jan;67(1):25-36.
    PMID: 39585369 DOI: 10.1007/s00234-024-03510-z
    PURPOSE: The study aims to evaluate the magnetic resonance (MR) features of central nervous system (CNS) fungal infections and determine the associations between these findings and the type of fungus. Our main objective was to assess whether imaging can serve as a predictor for identifying the specific group of fungi responsible for the infection using microbiology and histopathology as a benchmark.

    MATERIALS AND METHODS: A retrospective analysis was done on 50 patients with proven CNS fungal infections. Fungal type was determined and grouped according to microbial classifications into four subtypes: hyalohyphomycetes, mucorales, yeasts and dematiaceous molds. MR findings were compared with histopathology/microbiology and associations between fungal groups were sought.

    RESULTS: A total of 37 males and 13 females with a mean age of 39.3 years were included in the study. Aspergillus spp. infection (48%) was the most common. Most patients (54%) had an underlying risk factor for the infection. Pseudo-tumoral mass-like behavior was observed with Aspergillus, and the presence of meningitis was associated with yeast infections (p 

    MeSH terms: Adolescent; Adult; Aged; Child; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Retrospective Studies
  4. Ibrahim NNIN, Rasool AHG, Rahman RA, Azlan M, Aziz AA
    Microvasc Res, 2025 Mar;158:104772.
    PMID: 39586372 DOI: 10.1016/j.mvr.2024.104772
    BACKGROUND: Pulse wave analysis (PWA) assesses endothelial dependent vasodilation (EDV) via the change in augmentation index (AIx) and has been used as a tool to assess endothelial function. However, its effectiveness in assessing the response to lipid lowering treatment has not been evaluated. The study aimed to describe and correlate the change in EDV following lipid lowering intervention in patients with hypercholesterolemia.

    METHODS: 48 newly diagnosed patients with hypercholesterolemia underwent 6 months intervention with statin and/or therapeutic lifestyle changes (TLC) in clinical setting. Lipid profile measurement and endothelial function assessment using PWA were performed pre- and post-intervention.

    RESULTS: Significant reductions in low density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (non-HDL-C) and total cholesterol (TC) with corresponding significant improvement in EDV (2.94 ± 3.69 % to 7.50 ± 3.79 %, p 

    MeSH terms: Adult; Aged; Female; Humans; Lipids/blood; Cholesterol, LDL/blood; Male; Middle Aged; Predictive Value of Tests; Time Factors; Treatment Outcome; Pulse Wave Analysis*
  5. Seri AFD, Arendt M
    J Hum Lact, 2025 Feb;41(1):10-15.
    PMID: 39588693 DOI: 10.1177/08903344241297589
    Anwar Fazal has been a driving force in the founding of several civil society organizations in the areas of health, human rights, environment, and peace, that have been at the forefront of activism locally, nationally, and globally. In this interview, he shares his journey of 6 decades, involving a multiverse of public interest issues, which led him into the breastfeeding movement. It began with the setting up of the International Baby Food Action Network (IBFAN), a pioneering action that triggered the formation of Health Action International (HAI), Pesticide Action Network (PAN), and the World Alliance for Breastfeeding Action (WABA). Each of these resulted in several unique frameworks and codes relating to the marketing of infant foods, pharmaceuticals, and pesticides. They also led to the formation of World Breastfeeding Week, now being celebrated globally. Anwar studied Economics at the University of Malaya and did his postgraduate studies in Education. Anwar has served as a visiting professor at the University of Science Malaysia and the International Islamic University Malaysia (IIUM). He is the recipient of the Right Livelihood Award, popularly known as the "Alternative Nobel Prize," for his work on breastfeeding and infant nutrition and other health, environmental, and consumer issues. La Leche League International (LLLI) and the United Nations Development Programme (UNDP) have honored him with the International Health Award and the Millennium Development Goals Award. He has written extensively on breastfeeding. He is currently Chairperson Emeritus of the World Alliance for Breastfeeding Action (WABA) and continues to speak out actively on protecting, promoting, and supporting breastfeeding.
    MeSH terms: Female; Health Promotion/history; Health Promotion/methods; Humans; History, 20th Century; History, 21st Century
  6. Acharya M, Deo RC, Tao X, Barua PD, Devi A, Atmakuru A, et al.
    Comput Methods Programs Biomed, 2025 Feb;259:108506.
    PMID: 39581069 DOI: 10.1016/j.cmpb.2024.108506
    BACKGROUND AND OBJECTIVES: Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) are progressive neurological disorders that significantly impair the cognitive functions, memory, and daily activities. They affect millions of individuals worldwide, posing a significant challenge for its diagnosis and management, leading to detrimental impacts on patients' quality of lives and increased burden on caregivers. Hence, early detection of MCI and AD is crucial for timely intervention and effective disease management.

    METHODS: This study presents a comprehensive systematic review focusing on the applications of deep learning in detecting MCI and AD using electroencephalogram (EEG) signals. Through a rigorous literature screening process based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the research has investigated 74 different papers in detail to analyze the different approaches used to detect MCI and AD neurological disorders.

    RESULTS: The findings of this study stand out as the first to deal with the classification of dual MCI and AD (MCI+AD) using EEG signals. This unique approach has enabled us to highlight the state-of-the-art high-performing models, specifically focusing on deep learning while examining their strengths and limitations in detecting the MCI, AD, and the MCI+AD comorbidity situations.

    CONCLUSION: The present study has not only identified the current limitations in deep learning area for MCI and AD detection but also proposes specific future directions to address these neurological disorders by implement best practice deep learning approaches. Our main goal is to offer insights as references for future research encouraging the development of deep learning techniques in early detection and diagnosis of MCI and AD neurological disorders. By recommending the most effective deep learning tools, we have also provided a benchmark for future research, with clear implications for the practical use of these techniques in healthcare.

    MeSH terms: Humans
  7. Tan SY, Foo CN, Ng FL, Tan CH, Lim YM
    Gene, 2025 Jan 30;935:149043.
    PMID: 39486662 DOI: 10.1016/j.gene.2024.149043
    Breast cancer remains a significant global health concern, impacting millions of women every year. Maslinic acid (MA), a pentacyclic triterpene has been found to exert promising anticancer effect in various cancers, including breast cancer, yet the underlying mechanisms remain unclear. This study aims to elucidate the anticancer properties of MA via gene expression profiles in breast cancer cells. Cytotoxicity assay results revealed that MCF-7 exerts the highest sensitivity after 72 h of MA treatment followed by T-47D and MDA-MB-231. MCF-7 were then selected for in-depth analysis using the Nanostring nCounter Pancancer Pathway Panel to analyze the differential expression of genes (DEGs). Across three time points (24, 48, and 72 h), 20 significant DEGs were identified, of which 5 were upregulated and 15 were downregulated. In silico analysis indicated that these DEGs were involved in Pathway of Cancer, Focal Adhesion-PI3K-mTOR Signaling Pathway, PI3K-Akt, and Ras Signaling Pathway. The regulation of these DEGs contributes to several cellular activities such as apoptosis, inhibition of cell proliferation, cell cycle and survival, reduction of glycolysis, angiogenesis, and DNA repair. Additionally, the unfolded protein response emerged as a noteworthy biological process in this study. This study unravels the molecular mechanisms underpinning the therapeutic potential of MA against breast cancer.
    MeSH terms: Female; Humans; Oleanolic Acid/analogs & derivatives; Apoptosis/drug effects; Cell Line, Tumor; Cell Proliferation/drug effects; MCF-7 Cells
  8. Almassri HF, Abdul Kadir A, Srour M, Foo LH
    Clin Nutr ESPEN, 2025 Feb;65:64-75.
    PMID: 39577691 DOI: 10.1016/j.clnesp.2024.11.014
    BACKGROUND AND AIMS: Nutritional intervention is one of the primary steps to improvement of health status and quality of life (QoL) in patients with cancer treated by chemotherapy. There is limited evidence on the potential nutritional intervention to complement active oncological treatment strategies in breast cancer (BC) patients in developing countries. The aim of the present study was to assess the effects of omega-3 fatty acids (ω3) and vitamin D3 (VitD) supplementations on the QoL and blood inflammation markers of tumor necrosis factor-alpha (TNF-α) and high-sensitive C-reactive protein (hsCRP) assessed among women newly diagnosed with BC in the Gaza Strip, Palestine.

    METHODS: A total of 88 BC women were randomly assigned into one of four groups: i) omega-3 fatty acid (ω3) group; ii) vitamin D (VitD) group; iii) ω3+VitD group, and iv) the control. Participants were received either two 300 mg ω3 capsules daily, or one 50,000IU VitD tablet weekly, or both supplementation for 9-weeks. The QoL status was assessed by the European Organization for Research and Treatment of Cancer (EORTC) instruments of QLQ-C30 and QLQ-BR23 tools, while blood inflammatory markers of TNF-α hsCRP were used. All measurements were taken from baseline to the end of the intervention period. The detailed procedures of the present study were registered on ClinicalTrial.gov with the identifier NCT05331807.

    RESULTS: At the end of the trial, participants in the ω3+VitD group showed a significant increase in overall global health status (p 

    MeSH terms: Adult; Cholecalciferol/administration & dosage; Cholecalciferol/therapeutic use; Female; Humans; Middle Aged; Quality of Life*; Vitamin D/administration & dosage; Vitamin D/blood; Dietary Supplements*
  9. Hussain A, Gorsi FI, Ali MQ, Yaqub S, Asif A, Bibi B, et al.
    Food Chem, 2025 Feb 15;465(Pt 2):142129.
    PMID: 39579399 DOI: 10.1016/j.foodchem.2024.142129
    Valorizing neglected crop byproducts through eco-friendly techniques has gained attention as underutilized crops offer new sources of bioactive components. This study examined the chemical composition, phytochemicals, and antioxidant activities in six fractions of the underutilized chayote (Sechium edule). Each fraction was microwave-dried and extracted with ultrasound assistance. Shoots were high in ash and fiber, while pulp had high moisture and carbohydrates, and seeds were rich in fat and protein. Shoots, leaves, roots, and peels had high mineral levels, particularly Ca, K, Mg, P, Fe, and Zn. Shoots were also high in phenolics, flavonoids, and ascorbic acid, while leaves had a high carotenoid content. Polyphenol compounds such as myricetin and catechin were abundant in shoots, which exhibited the highest antioxidant activity. Chayote shoots, roots, and leaves are abundant in bioactive compounds that can be utilized in food and, therefore, offers an opportunity for utilization of a currently neglected plant byproduct.
    MeSH terms: Desiccation; Flavonoids/analysis; Flavonoids/chemistry; Phenols/analysis; Phenols/chemistry; Seeds/chemistry; Plant Leaves/chemistry; Plant Roots/chemistry; Phytochemicals/isolation & purification; Phytochemicals/chemistry
  10. Wu H, Yu M, Huang J, Zhang Q, Yao R, Liu H, et al.
    Mar Pollut Bull, 2025 Jan;210:117317.
    PMID: 39579595 DOI: 10.1016/j.marpolbul.2024.117317
    Organophosphate esters (OPEs) are emerging pollutants and used extensively in industrial production as alternative to the traditional flame retardants. This study investigated the contamination characteristics and health risks of OPEs in 104 mollusks from 15 cities along the coastal region of South China. Σ8OPEs ranged from 48.2 to 1937 ng/g dw, with a mean value of 295 ng/g dw. TDCIPP, TCPP, and TCEP were the dominant OPEs. Different spatial distributions were observed, with higher concentrations in Guangdong Province. A statistically positive but non-significant linear correlation was found between the trophic level of mollusk and OPEs concentration. The trophic magnification factors were >1, suggesting that OPEs have the potential to biomagnify in mollusks. OPEs in mollusks pose low non-carcinogenic and carcinogenic risks to consumers. This study provides an important basis for managing the safety risks associated with OPEs in mollusks.
    MeSH terms: Animals; China; Environmental Monitoring*; Flame Retardants/analysis; Mollusca*; Risk Assessment
  11. Prithula J, Islam KR, Kumar J, Tan TL, Reaz MBI, Rahman T, et al.
    Comput Biol Med, 2025 Jan;184:109284.
    PMID: 39579661 DOI: 10.1016/j.compbiomed.2024.109284
    Sepsis, a life-threatening condition triggered by the body's response to infection, remains a significant global health challenge, annually affecting millions in the United States alone with substantial mortality and healthcare costs. Early prediction of sepsis is critical for timely intervention and improved patient outcomes. This study introduces an innovative predictive model leveraging machine learning techniques and a specific data-splitting approach on highly imbalanced electronic health records (EHRs). Using PhysioNet/CinC Challenge 2019 data from 40,336 patients, including vital signs, lab values, and demographics. Preliminary assessments using classical and stacked ML models with Synthetic Minority Oversampling Technique (SMOTE) augmentation were conducted, showing improved performance. It is found that stacking ML models enhances overall accuracy but faces limitations in precision, recall, and F1 score for positive class prediction. A novel data-splitting approach with 5-fold cross-validation and SMOTE and COPULA augmentation techniques demonstrated promise, with F1 scores ranging from 93 % to 94 % using the COPULA technique. COPULA excelled at predictions for different hours' onsets compared to the SMOTE technique. The proposed model outperformed existing studies, suggesting clinical viability for early sepsis prediction.
    MeSH terms: Machine Learning*; Female; Humans; Intensive Care Units*; Male; Electronic Health Records*
  12. Yong MY, Tan KY, Tan CH
    PMID: 39579840 DOI: 10.1016/j.cbpc.2024.110077
    High molecular weight proteins are present abundantly in viperid venoms. The amino acid sequence can be highly variable, contributing to the structure and function diversity of snake venom protein. However, this variability remains poorly understood in many species. The study investigated the venom protein variability in a distinct clade of Asian pit vipers (Trimeresurus species complex) through comparative proteomics, applying gel electrophoresis (SDS-PAGE), liquid chromatography-tandem mass spectrometry (LCMS/MS), and bioinformatic approaches. The proteomes revealed a number of conserved protein families, within each are variably expressed protein paralogs that are unrelated to the snake phylogeny and geographic origin. The expression levels of two major enzymes, i.e., snake venom serine proteinase and metalloproteinase, correlate weakly with procoagulant and hemorrhagic activities, implying co-expression of other functionally versatile toxins in the venom. The phospholipase A2 (PLA2) abundance correlates strongly with its enzymatic activity, and a unique phenotype was discovered in two species expressing extremely little PLA2. The commercial mono-specific antivenom effectively neutralized the venoms' procoagulant and hemorrhagic effects but failed to inhibit the PLA2 activities. Instead, the PLA2 activities of all venoms were effectively inhibited by the small molecule inhibitor varespladib, suggesting its potential to be repurposed as a highly potent adjuvant therapeutic in snakebite envenoming.
    MeSH terms: Animals; Antivenins/pharmacology; Phylogeny; Species Specificity; Reptilian Proteins/antagonists & inhibitors; Reptilian Proteins/genetics; Reptilian Proteins/metabolism; Proteomics/methods; Phospholipase A2 Inhibitors/pharmacology
  13. Lee FCH, Sitam FT, Tan LP
    J Virol Methods, 2025 Feb;332:115074.
    PMID: 39580121 DOI: 10.1016/j.jviromet.2024.115074
    DNA samples selected for long read sequencing (LRS) are routinely required to be 'pure' with high DNA concentration. Hence the usefulness of samples with substandard DNA quality for LRS is unknown. We aim to perform de-novo assembly of Adenovirus sequenced from non-human primate (NHP) faeces using the Oxford Nanopore technologies (ONT), an LRS platform. Guided by initial conventional PCR screening, we performed ONT sequencing on 34 Adenovirus positive DNA samples, without prior selection based on faeces freshness level or DNA quality. Non-parametric correlation analysis showed that ONT sequencing outputs is not significantly associated (p > 0.05) with DNA concentrations, faeces freshness levels and the OD ratios of A260/A280 and A260/A230. This indicated that conventional DNA quality parameters may not be the most critical factors in determining the suitability of samples for ONT sequencing. A total of 61.76 % (21/34) of the positive-by-PCR-screening samples yielded Adenovirus reads while 38.24 % (13/34) did not in the PCR-free ONT workflow, although rarefaction analysis showed that sequencing saturation was achieved by all samples. Among the 21 samples with adenovirus reads, ten resulted in at least one Adenovirus contig by the Flye assembler while nine did not and two samples had only a single Adenovirus read. Identity similarity above 90 % in conventional PCR screening may help in selecting ONT positive samples.
    MeSH terms: Adenoviridae Infections/diagnosis; Adenoviridae Infections/veterinary; Adenoviridae Infections/virology; Animals; Primates/virology; Polymerase Chain Reaction/methods; Sequence Analysis, DNA; High-Throughput Nucleotide Sequencing/methods; High-Throughput Nucleotide Sequencing/standards
  14. Lagutkin D, Panaifo L, Nurul-Aain AF, Israelsson L, Hansson M, Lundberg K, et al.
    ACR Open Rheumatol, 2025 Jan;7(1):e11767.
    PMID: 39576054 DOI: 10.1002/acr2.11767
    OBJECTIVE: Autoantibodies serve as essential clinical biomarkers and may indicate etiological mechanisms in rheumatic diseases. In light of the increasing knowledge concerning the diversity and biologic implications of anti-citrullinated peptide/protein antibodies (ACPAs), we have re-evaluated the association between the ACPA response and the HLA-DRB1 allelic groups, known to represent a major genetic risk factor for rheumatoid arthritis (RA).

    METHODS: We explored a collection of 4,392 well-characterized incident patients with RA of White European descent from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) new-onset RA study, as well as 1,199 cases of patients with RA of Southeast Asian origin from the Malaysian EIRA study. We focused on a quantitative analysis of the levels of anti-cyclic citrullinated peptide IgG antibodies, including those falling below the diagnostic threshold.

    RESULTS: Our data show that non-shared epitope alleles HLA-DRB1*09 and *15 exhibit significant associations with ACPA levels. Notably, these novel associations were independent of ethnicity. To validate our findings, we conducted an additional replication study in an independent pool of 4,109 patients with RA of White European origin.

    CONCLUSION: These results indicate a new, previously overlooked, role for the HLA locus in the regulation of the levels of ACPA RA-specific autoantibodies that goes beyond the shared epitope-defined gene variants.

  15. Yılmaz MK, Baochao J, Çakır N, Uzun A, Abbas AA, Culp B, et al.
    J Arthroplasty, 2025 Feb;40(2S1):S52-S54.
    PMID: 39428011 DOI: 10.1016/j.arth.2024.10.032
  16. Lee ZH, Tung WS, Santhiran KAJ, Shahzad H, Giribabu N, Salleh N
    Pflugers Arch, 2025 Feb;477(2):317-332.
    PMID: 39570400 DOI: 10.1007/s00424-024-03032-w
    This study aims to investigate the effect of estrogen hindrance, i.e., menopause in women for instance with rheumatoid arthritis on the brain hippocampal region by using collagen-induced arthritis (CIA) female rat model (RA). CIA was induced in female rats by injecting bovine type II collagen and incomplete Freund's adjuvant. Estrogen receptor antagonist, fulvestrant (Ful), was given to RA rats to create estrogen hindrance. Control (C) and RA rats were injected with saline and DMSO, respectively, while RA + Ful rats received a 7-day fulvestrant injection. Following experiment completion, rats were sacrificed, and brains were harvested. Brains were stained with H&E and cresyl violet staining and morphological changes in the hippocampus were identified. Additionally, oxidative stress, inflammatory, and apoptosis markers' levels in the hippocampus were analyzed by qPCR, ELISA, and immunohistochemistry techniques. RA + Ful rats showed neuronal atrophy and reduced neurogenesis in the hippocampal regions. NOX4, NF-κB, IL-1β, IL-6, TNF-α, IKK-β, and Bax protein expression levels in the hippocampus were increased, whereas hippocampal Bcl-2, caspase-3, caspase-9, and IGF-1R protein expression levels were decreased. Furthermore, RA + Ful rats had lower levels of antioxidants PON-1 and catalase in the hippocampal regions. The changes in these molecular markers were statistically significant when compared to RA rats without Ful treatment (p 
    MeSH terms: Animals; Arthritis, Rheumatoid/metabolism; Arthritis, Rheumatoid/pathology; Estradiol/pharmacology; Female; Rats, Sprague-Dawley*; Apoptosis/drug effects; Oxidative Stress/drug effects; Rats
  17. Chew EG, Liu Z, Li Z, Chung SJ, Lian MM, Tandiono M, et al.
    Nat Aging, 2025 Feb;5(2):205-218.
    PMID: 39572736 DOI: 10.1038/s43587-024-00760-7
    Parkinson's disease (PD) is an incurable, progressive and common movement disorder that is increasing in incidence globally because of population aging. We hypothesized that the landscape of rare, protein-altering variants could provide further insights into disease pathogenesis. Here we performed whole-exome sequencing followed by gene-based tests on 4,298 PD cases and 5,512 controls of Asian ancestry. We showed that GBA1 and SMPD1 were significantly associated with PD risk, with replication in a further 5,585 PD cases and 5,642 controls. We further refined variant classification using in vitro assays and showed that SMPD1 variants with reduced enzymatic activity display the strongest association (<44% activity, odds ratio (OR) = 2.24, P = 1.25 × 10-15) with PD risk. Moreover, 80.5% of SMPD1 carriers harbored the Asian-specific p.Pro332Arg variant (OR = 2.16; P = 4.47 × 10-8). Our findings highlight the utility of performing exome sequencing in diverse ancestry groups to identify rare protein-altering variants in genes previously unassociated with disease.
    MeSH terms: Aged; Female; Glucosylceramidase/genetics; Humans; Male; Middle Aged; Risk Factors; Genetic Variation/genetics; Case-Control Studies; Genetic Predisposition to Disease*; Exome/genetics
  18. Ten KE, Rahman S, Tan HS
    FEBS Lett, 2025 Jan;599(1):120-139.
    PMID: 39572900 DOI: 10.1002/1873-3468.15061
    Acinetobacter baumannii, a top-priority WHO pathogen, causes life-threatening infections in immunocompromised patients, leading to prolonged hospitalisation and high mortality. Here, we used the Galleria mellonella model to investigate community strain C98 (Ab-C98) virulence via transcriptomic analysis. Ab-C98 showed greater killing and faster colonisation in larvae than the clinical reference strain (ATCC BAA1605). Genes in three iron clusters, acinetobactin, baumannoferrin and the Feo system, were significantly up-regulated. Targeted knockout of siderophore genes (basC, bfnD, and the gene encoding isochorismatase) significantly increased the survival of infected larvae by at least 35.16%, identifying these genes as potential targets for developing anti-virulence agents against A. baumannii.
    MeSH terms: Animals; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Imidazoles; Larva/microbiology; Moths/microbiology; Oxazoles; Virulence/genetics; Gene Expression Regulation, Bacterial; Gene Expression Profiling; Transcriptome*
  19. Chauhan K, Royse A, Goh I, Crozier I, Wynn G
    J Cardiovasc Electrophysiol, 2025 Jan;36(1):295-297.
    PMID: 39575491 DOI: 10.1111/jce.16511
    INTRODUCTION: Substernal extravascular defibrillators (EV ICDs) have been shown to be effective and safe for patients at risk of sudden cardiac death, however, there is little evidence around the safety of extracting chronic devices.

    METHODS AND RESULTS: We present a 50-year-old patient in whom a Medtronic EV ICD system was successfully removed without specialist extraction tools, 186 weeks after implantation, by an operator experienced in transvenous lead extraction but without formal training in EVICD implantation.

    CONCLUSION: The successful extraction of an EV ICD system is possible without specialised tools at least 3.6 years post-implant.

    MeSH terms: Humans; Male; Middle Aged; Prosthesis Design; Time Factors; Treatment Outcome; Defibrillators, Implantable*; Device Removal*
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