Displaying publications 21 - 36 of 36 in total

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  1. Fulltext Identification and genomic analysis of temperate Halomonas bacteriophage vB_HmeY_H4907 from the surface sediment of the Mariana Trench at a depth of 8,900 m
    Su Y, Zhang W, Liang Y, Wang H, Liu Y, Zheng K, et al.
    Microbiol Spectr, 2023 Sep 20;11(5):e0191223.
    PMID: 37728551 DOI: 10.1128/spectrum.01912-23
    Viruses play crucial roles in the ecosystem by modulating the host community structure, mediating biogeochemical cycles, and compensating for the metabolism of host cells. Mariana Trench, the world's deepest hadal habitat, harbors a variety of unique microorganisms that have adapted to its extreme conditions of low temperatures, high pressure, and nutrient scarcity. However, our knowledge about isolated hadal phage strains in the hadal trench is still limited. This study reported the discovery of a temperate phage, vB_HmeY_H4907, infecting Halomonas meridiana H4907, isolated from surface sediment from the Mariana Trench at a depth of 8,900 m. To our best knowledge, it is the deepest isolated siphovirus from the ocean. Its 40,452 bp linear dsDNA genome has 57.64% GC content and 55 open reading frames, and it is highly homologous to its host. Phylogenetic analysis and average nucleotide sequence identification reveal that vB_HmeY_H4907 is separated from the isolated phages and represents a new family, Suviridae, with eight predicted proviruses and six uncultured viral genomes. They are widely distributed in the ocean, suggesting a prevalence of this viral family in the deep sea. These findings expand our understanding of the phylogenetic diversity and genomic features of hadal lysogenic phages, provide essential information for further studies of phage-host interactions and evolution, and may reveal new insights into the lysogenic lifestyles of viruses inhabiting the hadal ocean. IMPORTANCE Halomonas phage vB_HmeY_H4907 is the deepest isolated siphovirus from the ocean, and it represents a novel abundant viral family in the ocean. This study provides insights into the genomic, phylogenetic, and ecological characteristics of the new viral family, namely, Suviridae.
  2. Genome analysis of vB_SupP_AX, a novel N4-like phage infecting Sulfitobacter
    Liu Y, Zhu C, Liang Y, McMinn A, Zheng K, Wang Z, et al.
    Int Microbiol, 2024 Jan 08.
    PMID: 38190086 DOI: 10.1007/s10123-023-00476-5
    Sulfitobacter is a bacterium recognized for its production of AMP-independent sulfite oxidase, which is instrumental in the creation of sulfite biosensors. This capability underscores its ecological and economic relevance. In this study, we present a newly discovered phage, Sulfitobacter phage vB_SupP_AX, which was isolated from Maidao of Qingdao, China. The vB_SupP_AX genome is linear and double-stranded and measures 75,445 bp with a GC content of 49%. It encompasses four transfer RNA (tRNA) sequences and 79 open reading frames (ORFs), one of which is an auxiliary metabolic gene encoding thioredoxin. Consistent with other N4-like phages, vB_SupP_AX possesses three distinct RNA polymerases and is characterized by the presence of four tRNA molecules. Comparative genomic and phylogenetic analyses position vB_SupP_AX and three other viral genomes from the Integrated Microbial Genomes/Virus v4 database within the Rhodovirinae virus subfamily. The identification of vB_SupP_AX enhances our understanding of virus-host interactions within marine ecosystems.
  3. Muscle cellularity, growth performance and growth-related gene expression of juvenile climbing perch Anabas testudineus in response to different eggs incubation temperature
    Ahammad AKS, Asaduzzaman M, Uddin Ahmed MB, Akter S, Islam MS, Haque MM, et al.
    J Therm Biol, 2021 Feb;96:102830.
    PMID: 33627269 DOI: 10.1016/j.jtherbio.2020.102830
    Although indigenous climbing perch (Anabas testudineusis) is a highly valuable species, slow growth pattern during the culture period impeding its commercial success in aquaculture. In many fish species, it has been demonstrated that incubation temperature of eggs influenced the muscle development and growth rates, which persisted throughout the subsequent larval and juvenile phases. Therefore, this study aimed to investigate whether different incubation temperature of eggs prior to hatching can stimulate the muscle development, growth, and growth-related gene expression of the slow-growing indigenous species of climbing perch. The fertilized eggs of A. testudineus from an artificial breeding program were incubated under control temperature of 24 °C (IT24), 26 °C (IT26), 28 °C (IT28), and 30 °C (IT30) in 10L glass aquaria with four replicated units for each temperature treatment. After hatching, the larvae from each incubated temperature were separately reared at ambient temperature for 10 days in aquarium, 20 days in hapas, and the next 42 days in cages, totaling 72 days post-hatching (dph). The hatching rates were found significantly (P 
  4. Fulltext Molecular Characterization and Gene Expression of Glutathione Peroxidase 1 in Tor tambroides Exposed to Temperature Stress
    Do TD, Thi Mai N, Duy Khoa TN, Abol-Munafi AB, Liew HJ, Kim CB, et al.
    Evol Bioinform Online, 2019;15:1176934319853580.
    PMID: 31236006 DOI: 10.1177/1176934319853580
    Temperature is an abiotic factor that affects various biological and physiological processes in fish. Temperature stress is known to increase the production of reactive oxygen species (ROS) that subsequently cause oxidative stress. Fish is known to evolve a system of antioxidant enzymes to reduce ROS toxicology. Glutathione peroxidase (GPx) family consists of key enzymes that protect fish from oxidative stress. In this study, full-length GPx1 cDNA (GenBank accession no. KY984468) of Tor tambroides was cloned and characterized by rapid amplification of cDNA ends (RACE). The 899-base-pair (bp) GPx1 cDNA includes a 576-bp open reading frame encoding for 191 amino acids, plus 28 bp of 5'-untranslated region (UTR) and 295 bp of 3'-UTR. Homology analysis revealed that GPx1 of T tambroides (Tor-GPx1) shared high similarity with GPx1 sequences of other fish species. The phylogenetic construction based on the amino acid sequence showed that Tor-GPx1 formed a clade with GPx1 sequences of various fish species. Real-time polymerase chain reaction (PCR) was performed to assess the levels of GPx1 gene expression in the liver and muscle of T tambroides under thermal stress. The results indicated that GPx1 gene expression was down-regulated under decreased temperature. However, there was no significant difference between GPx1 gene expression in fish exposed to high temperature and control. Our study provides the first data regarding GPx gene expression in T tambroides under thermal stress.
  5. Fulltext Population Genomics of an Anadromous Hilsa Shad Tenualosa ilisha Species across Its Diverse Migratory Habitats: Discrimination by Fine-Scale Local Adaptation
    Asaduzzaman M, Igarashi Y, Wahab MA, Nahiduzzaman M, Rahman MJ, Phillips MJ, et al.
    Genes (Basel), 2019 12 30;11(1).
    PMID: 31905942 DOI: 10.3390/genes11010046
    The migration of anadromous fish in heterogenic environments unceasingly imposes a selective pressure that results in genetic variation for local adaptation. However, discrimination of anadromous fish populations by fine-scale local adaptation is challenging because of their high rate of gene flow, highly connected divergent population, and large population size. Recent advances in next-generation sequencing (NGS) have expanded the prospects of defining the weakly structured population of anadromous fish. Therefore, we used NGS-based restriction site-associated DNA (NextRAD) techniques on 300 individuals of an anadromous Hilsa shad (Tenualosa ilisha) species, collected from nine strategic habitats, across their diverse migratory habitats, which include sea, estuary, and different freshwater rivers. The NextRAD technique successfully identified 15,453 single nucleotide polymorphism (SNP) loci. Outlier tests using the FST OutFLANK and pcadapt approaches identified 74 and 449 SNPs (49 SNPs being common), respectively, as putative adaptive loci under a divergent selection process. Our results, based on the different cluster analyses of these putatively adaptive loci, suggested that local adaptation has divided the Hilsa shad population into two genetically structured clusters, in which marine and estuarine collection sites were dominated by individuals of one genetic cluster and different riverine collection sites were dominated by individuals of another genetic cluster. The phylogenetic analysis revealed that all the riverine populations of Hilsa shad were further subdivided into the north-western riverine (turbid freshwater) and the north-eastern riverine (clear freshwater) ecotypes. Among all of the putatively adaptive loci, only 36 loci were observed to be in the coding region, and the encoded genes might be associated with important biological functions related to the local adaptation of Hilsa shad. In summary, our study provides both neutral and adaptive contexts for the observed genetic divergence of Hilsa shad and, consequently, resolves the previous inconclusive findings on their population genetic structure across their diverse migratory habitats. Moreover, the study has clearly demonstrated that NextRAD sequencing is an innovative approach to explore how dispersal and local adaptation can shape genetic divergence of non-model anadromous fish that intersect diverse migratory habitats during their life-history stages.
  6. Fulltext Naturally Acquired Human Plasmodium cynomolgi and P. knowlesi Infections, Malaysian Borneo
    Raja TN, Hu TH, Kadir KA, Mohamad DSA, Rosli N, Wong LL, et al.
    Emerg Infect Dis, 2020 08;26(8):1801-1809.
    PMID: 32687020 DOI: 10.3201/eid2608.200343
    To monitor the incidence of Plasmodium knowlesi infections and determine whether other simian malaria parasites are being transmitted to humans, we examined 1,047 blood samples from patients with malaria at Kapit Hospital in Kapit, Malaysia, during June 24, 2013-December 31, 2017. Using nested PCR assays, we found 845 (80.6%) patients had either P. knowlesi monoinfection (n = 815) or co-infection with other Plasmodium species (n = 30). We noted the annual number of these zoonotic infections increased greatly in 2017 (n = 284). We identified 6 patients, 17-65 years of age, with P. cynomolgi and P. knowlesi co-infections, confirmed by phylogenetic analyses of the Plasmodium cytochrome c oxidase subunit 1 gene sequences. P. knowlesi continues to be a public health concern in the Kapit Division of Sarawak, Malaysian Borneo. In addition, another simian malaria parasite, P. cynomolgi, also is an emerging cause of malaria in humans.
  7. Fulltext Characterization and genomic analysis of Stutzerimonas stutzeri phage vB_PstS_ZQG1, representing a novel viral genus
    Ge F, Guo R, Liang Y, Chen Y, Shao H, Sung YY, et al.
    Virus Res, 2023 Oct 15;336:199226.
    PMID: 37739268 DOI: 10.1016/j.virusres.2023.199226
    Stutzerimonas stutzeri is an opportunistic pathogenic bacterium belonging to the Gammaproteobacteria, exhibiting wide distribution in the environment and playing significant ecological roles such as nitrogen fixation or pollutant degradation. Despite its ecological importance, only two S. stutzeri phages have been isolated to date. Here, a novel S. stutzeri phage, vB_PstS_ZQG1, was isolated from the surface seawater of Qingdao, China. Transmission electron microscopy analysis indicates that vB_PstS_ZQG1 has a morphology characterized by a long non-contractile tail. The genomic sequence of vB_PstS_ZQG1 contains a linear, double-strand 61,790-bp with the G+C content of 53.24% and encodes 90 putative open reading frames. Two auxiliary metabolic genes encoding TolA protein and nucleotide pyrophosphohydrolase were identified, which are likely involved in host adaptation and phage reproduction. Phylogenetic and comparative genomic analyses demonstrated that vB_PstS_ZQG1 exhibits low similarity with previously isolated phages or uncultured viruses (average nucleotide identity values range from 21.7 to 29.4), suggesting that it represents a novel viral genus by itself, here named as Fuevirus. Biogeographic analysis showed that vB_PstS_ZQG1 was only detected in epipelagic and mesopelagic zone with low abundance. In summary, our findings of the phage vB_PstS_ZQG1 will provide helpful insights for further research on the interactions between S. stutzeri phages and their hosts, and contribute to discovering unknown viral sequences in the metagenomic database.
  8. Fulltext Cyst viability and stress tolerance upon heat shock protein 70 knockdown in the brine shrimp Artemia franciscana
    Iryani MTM, Sorgeloos P, Danish-Daniel M, Tan MP, Wong LL, Mok WJ, et al.
    Cell Stress Chaperones, 2020 Nov;25(6):1099-1103.
    PMID: 32383141 DOI: 10.1007/s12192-020-01113-0
    Females of the brine shrimp Artemia franciscana produce either free-swimming nauplii via ovoviviparous pathway of reproduction or encysted embryos, known as cysts, via oviparous pathway, in which biological processes are arrested. While previous study has shown a crucial role of ATP-dependent molecular chaperone, heat shock protein 70 (Hsp70) in protecting A. franciscana nauplii against various abiotic and abiotic stressors, the function of this protein in diapausing embryos and cyst development, however, remains unknown. RNA interference (RNAi) was applied in this study to examine the role of Hsp70 in cyst development and stress tolerance, with the latter performed by desiccation and freezing, a common method used for diapause termination in Artemia cysts. Hsp70 knockdown was apparent in cysts released from females that were injected with Hsp70 dsRNA. The loss of Hsp70 affected neither the development nor morphology of the cysts. The time between fertilization and cyst release from Artemia females injected with Hsp70 dsRNA was delayed slightly, but the differences were not significant when compared to the controls. However, the hatching percentage of cysts which lacks Hsp70 were reduced following desiccation and freezing. Taken together, these results indicated that Hsp70 possibly plays a role in the stress tolerance but not in the development of diapause-destined embryos of Artemia. This research makes fundamental contributions to our understanding of the role molecular chaperone Hsp70 plays in Artemia, an excellent model organism for diapause studies of the crustaceans.
  9. Fulltext Fine-scale population structure and ecotypes of anadromous Hilsa shad (Tenualosa ilisha) across complex aquatic ecosystems revealed by NextRAD genotyping
    Asaduzzaman M, Wahab MA, Rahman MJ, Nahiduzzzaman M, Dickson MW, Igarashi Y, et al.
    Sci Rep, 2019 11 05;9(1):16050.
    PMID: 31690767 DOI: 10.1038/s41598-019-52465-2
    The anadromous Hilsa shad (Tenualosa ilisha) live in the Bay of Bengal and migrate to the estuaries and freshwater rivers for spawning and nursing of the juveniles. This has led to two pertinent questions: (i) do all Hilsa shad that migrate from marine to freshwater rivers come from the same population? and (ii) is there any relationship between adults and juveniles of a particular habitat? To address these questions, NextRAD sequencing was applied to genotype 31,276 single nucleotide polymorphism (SNP) loci for 180 individuals collected from six strategic locations of riverine, estuarine and marine habitats. FST OutFLANK approach identified 14,815 SNP loci as putatively neutral and 79 SNP loci as putatively adaptive. We observed that divergent local adaptations in differing environmental habitats have divided Hilsa shad into three genetically structured ecotypes: turbid freshwater (Western Riverine), clear freshwater (Eastern Riverine) and brackish-saline (Southern Estuarine-Marine). Our results also revealed that genes involved in neuronal activity may have facilitated the juveniles' Hilsa shad in returning to their respective natal rivers for spawning. This study emphasized the application of fundamental population genomics information in strategizing conservation and management of anadromous fish such as Hilsa shad that intersect diverse ecotypes during their life-history stages.
  10. Putative Roles for Metallothionein and HSP70 Genes in Relation with Heavy Metal Accumulation and Parasitic Cymothoid in the Fish Nemipterus furcosus
    Thinh DD, Rasid MH, Deris ZM, Shazili NA, De Boeck G, Wong LL
    Arch Environ Contam Toxicol, 2016 Nov;71(4):530-540.
    PMID: 27638714
    To assess stress level induced by multiple stressors in aquatic organism, biomarkers have been adopted as early warning indicator due to their high accuracy, rapidity, and sensitivity. We investigated the effects of ectoparasitic isopod infection on heavy metal bioaccumulation (Fe, Cu, Zn, and Cd) in the fish Nemipterus furcosus and profiled the expression of metallothionein (MT) and heat shock proteins 70 (HSP70) genes of the fish host. Sixty individuals (parasitized and nonparasitized with Cymothoa truncata) were collected from three sites differing in the levels of anthropogenic activities off the South China Sea. Our results revealed no significant difference in heavy metal concentrations between infected and nonparasitized fish. We observed a positive correlation between heavy metal bioaccumulation in the fish host and anthropogenic activities. Accordingly, expression analysis of MT genes in fish liver showed significant differences in expression level between sampling sites, with lowest level in the least exploited site (Batu Rakit). A reverse pattern in HSP70 gene expression was demonstrated in fish muscle, showing the highest expression at Batu Rakit. While cymothoid infection in N. furcosus had no significant impact on fish MT gene expression, it resulted in a reduction of HSP70 level in liver of parasitized fish. These findings highlight the putative roles of MT in heavy metal assessment. Future studies should determine the kinetics of cymothoid infection and other potential stressors in characterizing the HSP70 gene expression profile.
  11. Fulltext Transcriptome Analysis and Differential Gene Expression on the Testis of Orange Mud Crab, Scylla olivacea, during Sexual Maturation
    Waiho K, Fazhan H, Shahreza MS, Moh JH, Noorbaiduri S, Wong LL, et al.
    PLoS One, 2017;12(1):e0171095.
    PMID: 28135340 DOI: 10.1371/journal.pone.0171095
    Adequate genetic information is essential for sustainable crustacean fisheries and aquaculture management. The commercially important orange mud crab, Scylla olivacea, is prevalent in Southeast Asia region and is highly sought after. Although it is a suitable aquaculture candidate, full domestication of this species is hampered by the lack of knowledge about the sexual maturation process and the molecular mechanisms behind it, especially in males. To date, data on its whole genome is yet to be reported for S. olivacea. The available transcriptome data published previously on this species focus primarily on females and the role of central nervous system in reproductive development. De novo transcriptome sequencing for the testes of S. olivacea from immature, maturing and mature stages were performed. A total of approximately 144 million high-quality reads were generated and de novo assembled into 160,569 transcripts with a total length of 142.2 Mb. Approximately 15-23% of the total assembled transcripts were annotated when compared to public protein sequence databases (i.e. UniProt database, Interpro database, Pfam database and Drosophila melanogaster protein database), and GO-categorised with GO Ontology terms. A total of 156,181 high-quality Single-Nucleotide Polymorphisms (SNPs) were mined from the transcriptome data of present study. Transcriptome comparison among the testes of different maturation stages revealed one gene (beta crystallin like gene) with the most significant differential expression-up-regulated in immature stage and down-regulated in maturing and mature stages. This was further validated by qRT-PCR. In conclusion, a comprehensive transcriptome of the testis of orange mud crabs from different maturation stages were obtained. This report provides an invaluable resource for enhancing our understanding of this species' genome structure and biology, as expressed and controlled by their gonads.
  12. De novo whole genome sequencing data of two mangrove-isolated microalgae from Terengganu coastal waters
    Teh KY, Afifudeen CLW, Aziz A, Wong LL, Loh SH, Cha TS
    Data Brief, 2019 Dec;27:104680.
    PMID: 31720332 DOI: 10.1016/j.dib.2019.104680
    Interest in harvesting potential benefits from microalgae renders it necessary to have the many ecological niches of a single species to be investigated. This dataset comprises de novo whole genome assembly of two mangrove-isolated microalgae (from division Chlorophyta); Chlorella vulgaris UMT-M1 and Messastrum gracile SE-MC4 from Universiti Malaysia Terengganu, Malaysia. Library runs were carried out with 2 × 150 base paired-ends reads, whereas sequencing was conducted using Illumina Novaseq 2500 platform. Sequencing yielded raw reads amounting to ∼11 Gb in total bases for both species and was further assembled de novo. Genome assembly resulted in a 50.15 Mbp and 60.83 Mbp genome size for UMT-M1 and SE-MC4, respectively. All filtered and assembled genomic data sequences have been submitted to National Centre for Biotechnology Information (NCBI) and can be located at DDBJ/ENA/GenBank under the accession of VJNP00000000 (UMT-M1) and VIYE00000000 (SE-MC4).
  13. Transcriptome-wide study in the green microalga Messastrum gracile SE-MC4 identifies prominent roles of photosynthetic integral membrane protein genes during exponential growth stage
    Wan Afifudeen CL, Aziz A, Wong LL, Takahashi K, Toda T, Abd Wahid ME, et al.
    Phytochemistry, 2021 Dec;192:112936.
    PMID: 34509143 DOI: 10.1016/j.phytochem.2021.112936
    The non-model microalga Messastrum gracile SE-MC4 is a potential species for biodiesel production. However, low biomass productivity hinders it from passing the life cycle assessment for biodiesel production. Therefore, the current study was aimed at uncovering the differences in the transcriptome profiles of the microalgae at early exponential and early stationary growth phases and dissecting the roles of specific differential expressed genes (DEGs) involved in cell division during M. gracile cultivation. The transcriptome analysis revealed that the photosynthetic integral membrane protein genes such as photosynthetic antenna protein were severely down-regulated during the stationary growth phase. In addition, the signaling pathways involving transcription, glyoxylate metabolism and carbon metabolism were also down-regulated during stationary growth phase. Current findings suggested that the coordination between photosynthetic integral membrane protein genes, signaling through transcription and carbon metabolism classified as prominent strategies during exponential growth stage. These findings can be applied in genetic improvement of M. gracile for biodiesel application.
  14. Fulltext Transcriptomics de novo sequencing data of Messastrum gracile SE-MC4 under exponential and stationary growth stages
    Afifudeen CLW, Loh SH, Wong LL, Aziz A, Takahashi K, Wahid MEA, et al.
    Data Brief, 2021 Dec;39:107607.
    PMID: 34869809 DOI: 10.1016/j.dib.2021.107607
    Messastrum gracile SE-MC4 is a non-model microalga exhibiting superior oil-accumulating abilities. However, biomass production in M. gracile SE-MC4 is limited due to low cell proliferation especially after prolonged cultivation under oil-inducing culture conditions. Present data consist of next generation RNA sequencing data of M. gracile SE-MC4 under exponential and stationary growth stages. RNA of six samples were extracted and sequenced with insert size of 100 bp paired-end strategy using BGISEQ-500 platform to produce a total of 59.64 Gb data with 314 million reads. Sequences were filtered and de novo assembled to form 53,307 number of gene sequences. Sequencing data were deposited in National Center for Biotechnology Information (NCBI) and can be accessed via BioProject ID PRJNA552165. This information can be used to enhance biomass production in M. gracile SE-MC4 and other microalgae aimed towards improving biodiesel development.
  15. Occurrence and the ecological implication of a tropical anguillid eel Anguilla marmorata from peninsular Malaysia
    Kadir SRA, Rasid MHFA, Kwong KO, Wong LL, Arai T
    Zookeys, 2017.
    PMID: 29134009 DOI: 10.3897/zookeys.695.13298
    Recent studies suggested that accurate species identification in the tropical anguillid eels based on morphological examination requires confirmation by molecular genetic analysis. Previous studies found that two tropical anguillid eels, Anguilla bicolor bicolor and A. bengalensis bengalensis, were found in peninsular Malaysia (West Malaysia) based on morphological and molecular genetic analyses. This study is the first record of A. marmorata in peninsular Malaysia confirmed by both morphological and molecular genetic analyses. The present study also suggests that accurate tropical eel species identification is difficult by morphological identification alone; therefore, molecular genetic analysis is needed for precise species confirmation.
  16. Fulltext Efficacy and Safety of Vagus Nerve Stimulation in Stroke Rehabilitation: A Systematic Review and Meta-Analysis
    Ananda R, Roslan MHB, Wong LL, Botross NP, Ngim CF, Mariapun J
    Cerebrovasc Dis, 2023;52(3):239-250.
    PMID: 36167034 DOI: 10.1159/000526470
    INTRODUCTION: Recent randomized controlled trials (RCTs) have assessed the role of vagus nerve stimulation (VNS) when paired with standard rehabilitation in stroke patients. This review aimed to evaluate the efficacy and safety of VNS as a novel treatment option for post-stroke recovery.

    METHODS: We searched PubMed, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL Plus for articles published from their date of inception to June 2021. RCTs investigating the efficacy or safety of VNS on post-stroke recovery were included. The outcomes were upper limb sensorimotor function, health-related quality of life, level of independence, cardiovascular effects, and adverse events. The risk of bias was assessed using the Cochrane risk-of-bias tool, while the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. Review Manager 5.4 was used to conduct the meta-analysis.

    RESULTS: Seven RCTs (n = 236 subjects) met the eligibility criteria. Upper limb sensorimotor function, assessed by the Fugl-Meyer Assessment for Upper Extremity (FMA-UE), improved at day 1 (n = 4 RCTs; standardized mean difference [SMD] 1.01; 95% confidence interval [CI]: 0.35-1.66) and day 90 post-intervention (n = 3 RCTs; SMD 0.64; 95% CI: 0.31-0.98; moderate certainty of evidence) but not at day 30 follow-up (n = 2 RCTs; SMD 1.54; 95% CI: -0.39 to 3.46). Clinically significant upper limb sensorimotor function recovery, as defined by ≥6 points increase in FMA-UE, was significantly higher at day 1 (n = 2 RCTs; risk ratio [RR] 2.01; 95% CI: 1.02-3.94) and day 90 post-intervention (n = 2 RCTs; RR 2.14; 95% CI: 1.32-3.45; moderate certainty of the evidence). The between-group effect sizes for upper limb sensorimotor function recovery was medium to large (Hedges' g 0.535-2.659). While the level of independence improved with VNS, its impact on health-related quality of life remains unclear as this was only studied in two trials with mixed results. Generally, adverse events reported were mild and self-limiting.

    CONCLUSION: VNS may be an effective and safe adjunct to standard rehabilitation for post-stroke recovery; however, its clinical significance and long-term efficacy and safety remain unclear.

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