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  1. Zhou LX, Xiao Y, Xia W, Yang YD
    Genet. Mol. Res., 2015;14(4):16247-54.
    PMID: 26662418 DOI: 10.4238/2015.December.8.15
    Genetic diversity and patterns of population structure of the 94 oil palm lines were investigated using species-specific simple sequence repeat (SSR) markers. We designed primers for 63 SSR loci based on their flanking sequences and conducted amplification in 94 oil palm DNA samples. The amplification result showed that a relatively high level of genetic diversity was observed between oil palm individuals according a set of 21 polymorphic microsatellite loci. The observed heterozygosity (Ho) was 0.3683 and 0.4035, with an average of 0.3859. The Ho value was a reliable determinant of the discriminatory power of the SSR primer combinations. The principal component analysis and unweighted pair-group method with arithmetic averaging cluster analysis showed the 94 oil palm lines were grouped into one cluster. These results demonstrated that the oil palm in Hainan Province of China and the germplasm introduced from Malaysia may be from the same source. The SSR protocol was effective and reliable for assessing the genetic diversity of oil palm. Knowledge of the genetic diversity and population structure will be crucial for establishing appropriate management stocks for this species.
  2. Zhou L, Wang P, Zhang J, Heng BC, Tong GQ
    Zygote, 2016 Feb;24(1):89-97.
    PMID: 25672483 DOI: 10.1017/S0967199414000768
    ING2 (inhibitor of growth protein-2) is a member of the ING-gene family and participates in diverse cellular processes involving tumor suppression, DNA repair, cell cycle regulation, and cellular senescence. As a subunit of the Sin3 histone deacetylase complex co-repressor complex, ING2 binds to H3K4me3 to regulate chromatin modification and gene expression. Additionally, ING2 recruits histone methyltransferase (HMT) activity for gene repression, which is independent of the HDAC class I or II pathway. However, the physiological function of ING2 in mouse preimplantation embryo development has not yet been characterized previously. The expression, localization and function of ING2 during preimplantation development were investigated in this study. We showed increasing expression of ING2 within the nucleus from the 4-cell embryo stage onwards; and that down-regulation of ING2 expression by endoribonuclease-prepared small interfering RNA (esiRNA) microinjection results in developmental arrest during the morula to blastocyst transition. Embryonic cells microinjected with ING2-specific esiRNA exhibited decreased blastulation rate compared to the negative control. Further investigation of the underlying mechanism indicated that down-regulation of ING2 significantly increased expression of p21, whilst decreasing expression of HDAC1. These results suggest that ING2 may play a crucial role in the process of preimplantation embryo development through chromatin regulation.
  3. Hss AS, Koh MT, Tan KK, Chan LG, Zhou L, Bouckenooghe A, et al.
    Vaccine, 2013 Dec 2;31(49):5814-21.
    PMID: 24135573 DOI: 10.1016/j.vaccine.2013.10.013
    Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia.
  4. Zhang Y, Zhou L, Zhang C, Show PL, Du A, Fu J, et al.
    Carbohydr Polym, 2020 Nov 01;247:116670.
    PMID: 32829798 DOI: 10.1016/j.carbpol.2020.116670
    With the growing interest in food safety and in environmental protection, it is more attractive to develop novel biodegradable packaging films. In this regard, one new blending film was prepared with curdlan (CD)/polyvinyl alcohol (PVA)/thyme essential oil. Our results demonstrated that the mechanical properties of the blending film were the best when the ratio of the CD and PVA was 4:1. Further, the barrier properties of the film were optimized by incorporating with thyme essential oil. It was proved that not only water vapor permeability was lower, but also the elongation at break was improved, when 2% (w/w) thyme essential oil used. The potential interactions of the film matrix were analyzed by FTIR, XRD and Cryo-scanning electron microscopy. Importantly, both the antioxidant activity and antibacterial activity were improved. Finally, the blending film was employed for the preservation of chilled meat, while the shelf life was extended up to 10 days.
  5. Xu W, Lee SH, Qiu F, Zhou L, Wang X, Ye T, et al.
    PLoS One, 2021;16(5):e0250634.
    PMID: 34048444 DOI: 10.1371/journal.pone.0250634
    BACKGROUND: Drug resistance frequently led to the failure of chemotherapy for malignant cancers, hence causing cancer relapse. Thus, understanding mechanism of drug resistance in cancer is vital to improve the treatment efficacy. Here, we aim to evaluate the association between SMAD4 expression and the drug resistance in cancers by performing a meta-analysis.

    METHOD: Relevant studies detecting SMAD4 expression in cancer patients treated with chemo-drugs up till December 2020 were systematically searched in four common scientific databases using selected keywords. The pooled hazard ratio (HR) was the ratio of hazard rate between SMAD4neg population vs SMAD4pos population. The HRs and risk ratios (RRs) with 95% confidence intervals (CIs) were used to explore the association between SMAD4 expression losses with drug resistance in cancers.

    RESULT: After an initial screening according to the inclusion and exclusion criteria, eleven studies were included in the meta-analysis. There were a total of 2092 patients from all the included studies in this analysis. Results obtained indicated that loss of SMAD4 expression was significantly correlated with drug resistance with pooled HRs (95% CI) of 1.23 (1.01-1.45), metastasis with pooled RRs (95% CI) of 1.10 (0.97-1.25) and recurrence with pooled RRs (95% CI) of 1.32 (1.06-1.64). In the subgroup analysis, cancer type, drug type, sample size and antibody brand did not affect the significance of association between loss of SMAD4 expression and drug resistance. In addition, there was no evidence of publication bias as suggested by Begg's test.

    CONCLUSION: Findings from our meta-analysis demonstrated that loss of SMAD4 expression was correlated with drug resistance, metastasis and recurrence. Therefore, SMAD4 expression could be potentially used as a molecular marker for cancer resistance.

  6. Dai C, Li S, Duan Y, Leong KH, Tu Y, Zhou L
    Sci Total Environ, 2021 Dec 20;801:149730.
    PMID: 34467938 DOI: 10.1016/j.scitotenv.2021.149730
    Pharmaceuticals in aquatic environment have raised wide attention in recent years due to their potential adverse effects and bioaccumulation in biota. China has been a major producer and consumer of pharmaceuticals, however, the potential human health risk of these chemicals is yet to be determined in China. In this study, we evaluated available exposure data for twenty pharmaceuticals in surface waters from Chinese five major river basins (the Yangtze, Haihe, Pearl, Songliao, and Yellow River Basins), and human health risk assessment was performed. Based on the concentration data and risk data, we conducted research on the source, cause, and control measures of the pharmaceuticals. The twenty pharmaceuticals were found to be ubiquitous in China with median concentrations between 0.09 and 304 ng/L. The estimated daily intake of pharmaceuticals from drinking water and eating fish was calculated. The intake via drinking water was significantly lower than that via eating fish. The risk quotients via water intake and fish consumption ranged from 0 to 17.2, with estrogen and sulfapyridine highest among the twenty pharmaceuticals. High risks of exposure were mainly in North China, including the Haihe and Songliao River Basins. This is the first analysis in Chinese major river basins that has filled the gaps in the research on the human health risks of pharmaceuticals. The results of the study provide basic information of pharmaceutical intake from drinking water and eating fish in China and provide insights into the risk management guidance of pharmaceuticals, and will facilitate the optimization of health advisories and policy making.
  7. Dai C, Han Y, Duan Y, Lai X, Fu R, Liu S, et al.
    Environ Res, 2022 Apr 01;205:112423.
    PMID: 34838568 DOI: 10.1016/j.envres.2021.112423
    The rapid economic and population growth in coastal areas is causing increasingly serious polycyclic aromatic hydrocarbons (PAHs) pollution in these regions. This review compared the PAHs pollution characteristics of different coastal areas, including industrial zones, commercial ports, touristic cities, aquacultural & agricultural areas, oil & gas exploitation areas and megacities. Currently there are various treatment methods to remediate soils and sediments contaminated with PAHs. However, it is necessary to provide a comprehensive overview of all the available remediation technologies up to date, so appropriate technologies can be selected to remediate PAHs pollution. In view of that, we analyzed the characteristics of the remediation mechanism, summarized the remediation methods for soil or sediments in coastal areas, which were physical repair, chemical oxidation, bioremediation and integrated approaches. Besides, this review also reported the development of new multi-functional green and sustainable systems, namely, micro-nano bubble (MNB), biochar, reversible surfactants and peracetic acid. While physical repair, expensive but efficient, was regarded as a suitable method for the PAHs remediation in coastal areas because of land shortage, integrated approaches would produce better results. The ultimate aim of the review was to ensure the successful restructuring of PAHs contaminated soil and sediments in coastal areas. Due to the environment heterogeneity, PAHs pollution in coastal areas remains as a daunting challenge. Therefore, new and suitable technologies are still needed to address the environmental issue.
  8. Zhou L, Song Y, Jiang Y, Wei Y, Jiang S, Chen Y, et al.
    Food Funct, 2023 Oct 02;14(19):8876-8892.
    PMID: 37698234 DOI: 10.1039/d3fo03041e
    Thinned peach fruit is a by-product with abundant yields. However, it is barely utilized. This study aimed to study the physicochemical properties and anti-diabetic ability of polysaccharides (PPSs) from a thinned peach fruit to investigate its application potential. Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM) characterizations were performed together with tests to determine rheology properties, monosaccharide composition, and molecular weight of the obtained polysaccharide. Moreover, the antioxidant activity, α-amylase inhibitory activity, binding abilities to bile salts, and effects on type 2 diabetic mice were analyzed. The results indicated that PPS consisted of two components with molecular weights of 287.38 kDa and 12.02 kDa, accounting for 89.83% and 10.17% of the composition, respectively. The dominant monosaccharides were galactose, galacturonic acid, and arabinose, exhibiting α-configurations. The concentration was positively related to the viscosity of PPS. As the temperature was increased from 25 °C to 37 °C and the pH from 2.0 to 7.0, the viscosity decreased. The IC50 values for scavenging DPPH and ABTS were around 0.22 and 1.47 mg mL-1. Also, PPS could inhibit α-amylase ability and bind bile salts. The administration of PPS significantly inhibited emaciation, organ damage, improved oral glucose tolerance and insulin resistance, enhanced the content of short-chain fatty acids (SCFAs), and regulated blood lipid profiles and the composition and structure of colon microbiota in type-2 diabetic mice. These results provide new evidence for the potential of PPS as a bioactive ingredient with anti-diabetic properties for use in the food industry.
  9. Cheng LE, Amoura Z, Cheah B, Hiepe F, Sullivan BA, Zhou L, et al.
    Arthritis Rheumatol, 2018 07;70(7):1071-1076.
    PMID: 29513931 DOI: 10.1002/art.40479
    OBJECTIVE: To evaluate the safety and potential efficacy of AMG 557, a fully human antibody directed against the inducible T cell costimulator ligand (ICOSL) in patients with systemic lupus erythematosus (SLE) with arthritis.

    METHODS: In this phase Ib, randomized, double-blind, placebo-controlled study, patients received AMG 557 210 mg (n = 10) or placebo (n = 10) weekly for 3 weeks, then every other week for 10 additional doses. The corticosteroid dosage was tapered to ≤7.5 mg/day by day 85, and immunosuppressants were discontinued by day 29. Primary end points on day 169 were safety, immunogenicity, the Lupus Arthritis Response Index (LARI; defined by a reduction in the tender and swollen joint counts), ≥1-letter improvement in the musculoskeletal domain of the British Isles Lupus Assessment Group (BILAG) index, and medication discontinuation. The secondary/exploratory end points were changes in the tender and swollen joint counts, BILAG index scores (musculoskeletal, global), and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).

    RESULTS: The incidence of adverse events, most of which were mild, was similar between groups. LARI responses occurred in 3 of 10 patients receiving AMG 557 and 1 of 10 patients receiving placebo (P = 0.58). More patients in the AMG 557 group achieved a ≥4-point improvement in the SLEDAI score on day 169 (7 of 10 patients) compared with the placebo group (2 of 10 patients) (P = 0.07). Patients treated with AMG 557 (versus placebo) had greater improvements from baseline in the global BILAG index scores (-36.3% versus -24.7%) and the SLEDAI score (-47.8% versus -10.7%) and in tender (-22.8% versus -13.5%) and swollen (-62.1% versus -7.8%) joint counts on day 169.

    CONCLUSION: AMG 557 showed safety and potential efficacy, supporting further evaluation of the clinical efficacy of ICOSL blockade in patients with SLE.

  10. Gao M, Sun Y, Wang Q, Ma S, Guo X, Zhou L, et al.
    PMID: 34523748 DOI: 10.1002/bab.2254
    Nanomaterial on the sensing area elevates the biomolecular immobilization by its right orientation with a proper alignment, and zeolite is one of the suitable materials. In this research, the zeolite nanoparticles were synthesized using rice hush ash as the basic source and the prepared zeolite by the addition of sodium silicate was utilized to attach antibody as a probe on a gap-fingered dielectrode surface to identify the colon cancer biomarker, "colon cancer-secreted protein-2" (CCSP-2). Field Emission Scanning Electron Microscopy and Field Emission Transmission Electron Microscopy images confirmed the size of the nanoparticle to be ∼15 nm and the occurrence of silica and alumina. Zeolite was modified on the electrode surface through the amine linker, and then anti-CCSP-2 was attached by an aldehyde linker. On this surface, CCSP-2 was detected and attained the detection limit to be 3 nM on the linear regression curve with 3-5 nM of CCSP-2. Estimated by the determination coefficient of y = 2.3952x - 4.4869 and R2 = 9041 with 3δ (n = 3). In addition, control proteins did not produce the notable current response representing the specific sensing of CCSP-2. This research is suitable to identify CCSP-2 at a lower level in the bloodstream under the physiological condition of a colon cancer patient.
  11. Sun S, Tan LT, Fang YL, Jin ZJ, Zhou L, Goh BH, et al.
    Mol Plant Microbe Interact, 2020 Mar;33(3):488-498.
    PMID: 31710580 DOI: 10.1094/MPMI-09-19-0264-R
    Phenazine-1-carboxylic acid (PCA) is the primary active component in the newly registered, commercial biopesticide Shenqinmycin and is produced during fermentation by the engineered rhizobacterium strain Pseudomonas PA1201. Both phz1 and phz2 gene clusters contribute to PCA biosynthesis. In this study, we evaluated the role of OxyR in the regulation of PCA biosynthesis in PA1201. We first showed a functional link between oxyR expression and PCA biosynthesis. Deletion of oxyR and overexpression of oxyR both increase PCA biosynthesis. The molecular mechanisms underlying OxyR regulation of PCA production were investigated using several approaches. OxyR acts divergently in phz1 and phz2. Overexpression of oxyR activated the expression of phz1 and phz1-dependent PCA production. However, overexpression of oxyR had little effect on phz2-dependent PCA biosynthesis, while deletion of oxyR promoted phz2-dependent PCA production and exerted a negative effect on phz2 expression. Further, OxyR directly bound to the phz2 promoter region. In addition, the regulation of PCA biosynthesis by OxyR was associated with quorum sensing (QS) systems. Overexpression of OxyR positively regulated pqs QS system. Finally, transcriptomic analysis and subsequent genetic analysis revealed the small RNA phrS plays a key role in OxyR-dependent PCA accumulation. Specifically, OxyR directly binds to the phrS promoter region to positively regulate phrS expression wherein PhrS regulates the PCA positive regulator MvfR in order to control PCA biosynthesis.
  12. Dai C, Shen H, Duan Y, You X, Lai X, Liu S, et al.
    PMID: 34505247 DOI: 10.1007/s11356-021-16266-3
    Nanomaterials are threatening the environment and human health, but there has been little discussion about the stability and mobility of nanoparticles (NPs) in saturated porous media at environmentally relevant concentrations of surfactants, which is a knowledge gap in exploring the fate of engineered NPs in groundwater. Therefore, the influences of the anionic surfactant (sodium dodecylbenzene sulfonate, SDBS), the cationic surfactant (cetyltrimethylammonium bromide, CTAB), and the nonionic surfactant (Tween-80) with environmentally relevant concentrations of 0, 5, 10, and 20 mg/L on nano-TiO2 (nTiO2, negatively charged) and nano-CeO2 (nCeO2, positively charged) transport through saturated porous media were examined by column experiments. On the whole, with increasing SDBS concentration from 0 to 20 mg/L, the concentration peak of nTiO2 and nCeO2 in effluents increased by approximately 0.2 and 0.3 (dimensionless concentration, C/C0), respectively, because of enhanced stability and reduced aggregate size resulting from enhanced electrostatic and steric repulsions. By contrast, the transportability of NPs significantly decreased with increasing CTAB concentration due to the attachment of positive charges, which was opposite to the charge on the medium surface and facilitated the NP deposition. On the other hand, the addition of Tween-80 had no significant influence on the stability and mobility of nTiO2 and nCeO2. The results were also demonstrated by the colloid filtration theory (CFT) modeling and the Derjaguin-Landau-Verwey-Overbeek (DLVO) interaction calculations; it might promote the assessment and remediation of NP pollution in subsurface environments.
  13. Zou JJ, Dai C, Hu J, Tong WK, Gao MT, Zhang Y, et al.
    Sci Total Environ, 2024 Apr 20;922:171201.
    PMID: 38417506 DOI: 10.1016/j.scitotenv.2024.171201
    Mycelial pellets formed by Penicillium thomii ZJJ were applied as efficient biosorbents for the removal of polycyclic aromatic hydrocarbons (PAHs), which are a type of ubiquitous harmful hydrophobic pollutants. The live mycelial pellets were able to remove 93.48 % of pyrene at a concentration of 100 mg/L within 48 h, demonstrating a maximum adsorption capacity of 285.63 mg/g. Meanwhile, the heat-killed one also achieved a removal rate of 65.01 %. Among the six typical PAHs (pyrene, phenanthrene, fluorene, anthracene, fluoranthene, benzo[a]pyrene), the mycelial pellets preferentially adsorbed the high molecular weight PAHs, which also have higher toxicity, resulting in higher removal efficiency. The experimental results showed that the biosorption of mycelial pellets was mainly a spontaneous physical adsorption process that occurred as a monolayer on a homogeneous surface, with mass transfer being the key rate-limiting step. The main adsorption sites on the surface of mycelia were carboxyl and N-containing groups. Extracellular polymeric substances (EPS) produced by mycelial pellets could enhance adsorption, and its coupling with dead mycelia could achieve basically the same removal effect to that of living one. It can be concluded that biosorption by mycelial pellets occurred due to the influence of electrostatic and hydrophobic interactions, consisting of five steps. Furthermore, the potential applicability of mycelial pellets has been investigated considering diverse factors. The mycelia showed high environmental tolerance, which could effectively remove pyrene across a wide range of pH and salt concentration. And pellets diameters and humic acid concentration had a significant effect on microbial adsorption effect. Based on a cost-effectiveness analysis, mycelium pellets were found to be a low-cost adsorbent. The research outcomes facilitate a thorough comprehension of the adsorption process of pyrene by mycelial pellets and their relevant applications, proposing a cost-effective method without potential environmental issues (heat-killed mycelial pellets plus EPS) to removal PAHs.
  14. Ng DS, Ho M, Chen LJ, Yip FL, Teh WM, Zhou L, et al.
    Am J Ophthalmol, 2021 12;232:70-82.
    PMID: 34116008 DOI: 10.1016/j.ajo.2021.05.029
    PURPOSE: To assess the diagnostic accuracy of optical coherence tomography angiography (OCTA) compared with multimodal imaging for choroidal neovascularization (CNV) in central serous chorioretinopathy (CSC) eyes and to determine the features that predicted CNV.

    DESIGN: Prospective cross-sectional study.

    METHODS: Consecutive CSC patients were recruited from retina clinic. The reference standard for CNV was determined by interpretation of multimodal imaging with OCTA, structural OCT line scan, fluorescein angiography (FA), indocyanine green angiography (ICGA), ultra-widefield fundus photography and fundus autofluorescence (FAF). Two independent masked graders examined OCTA without FA and ICGA to diagnose CNV. Univariate and multivariate analyses were performed to evaluate factors associated with CNV.

    RESULTS: CNV was detected in 69 eyes in 64 out of 277 CSC patients according to reference standard. The two masked graders who examined OCTA had sensitivity of 81.2% (95% Confidence Interval [CI], 71.9%-90.4%) and 78.3% (95% CI, 68.5%-88.0%), specificity of 97.3% (95% CI, 95.9%-98.8%) and 96.2% (95% CI, 94.5%-98.0%), positive predictive values of 82.4% (95% CI, 73.3%-91.4%) and 76.1% (95% CI, 66.1%-86.0%), and negative predictive values of 97.1% (95% CI, 95.6%-98.7%) and 96.7% (95% CI, 95.0%-98.3%). Their mean area under the receiver operating characteristic curve (AUC) was 0.88 with good agreement (Kappa coefficient 0.80 [95% CI, 0.72-0.89]). Flat irregular pigment epithelial detachment on structural OCT, neovascular network on OCTA and ill-defined late leakage on FA significantly correlated with CNV in CSC from multiple regression (P < 0.001, P < 0.001 and P = 0.005, respectively).

    CONCLUSIONS: There is discordance between OCTA and multimodal imaging in diagnosing CNV in CSC. This study demonstrated the caveats in OCTA interpretation, such as small extrafoveal lesions and retinal pigment epithelial alterations. Comprehensive interpretation of OCTA with dye angiography and structural OCT is recommended.

  15. Wang L, Tan H, Yu J, ZhangBao J, Huang W, Chang X, et al.
    Eur J Neurol, 2023 Feb;30(2):443-452.
    PMID: 36286605 DOI: 10.1111/ene.15612
    BACKGROUND AND PURPOSE: The aim was to evaluate the potential of retinal nerve fiber layer thickness (RNFLT) measured with optical coherence tomography in predicting disease progression in relapsing-remitting multiple sclerosis (RRMS).

    METHODS: Analyses were conducted post hoc of this 24-month, phase III, double-blind study, in which RRMS patients were randomized (1:1:1) to once daily oral fingolimod 0.5 mg, 1.25 mg or placebo. The key outcomes were the association between baseline RNFLT and baseline clinical characteristics and clinical/imaging outcomes up to 24 months. Change of RNFLT with fingolimod versus placebo within 24 months and time to retinal nerve fiber layer (RNFL) thinning were evaluated.

    RESULTS: Altogether 885 patients were included. At baseline, lower RNFLT was correlated with higher Expanded Disability Status Scale score (r = -1.085, p = 0.018), lower brain volume (r = 0.025, p = 0.006) and deep gray matter volume (r = 0.731, p 

  16. Tong WK, Dai C, Hu J, Li J, Gao MT, You X, et al.
    Sci Total Environ, 2024 Jan 10;907:168099.
    PMID: 37884130 DOI: 10.1016/j.scitotenv.2023.168099
    Nanobubbles (NBs), given their unique properties, could theoretically be paired with rhamnolipids (RL) to tackle polycyclic aromatic hydrocarbon contamination in groundwater. This approach may overcome the limitations of traditional surfactants, such as high toxicity and low efficiency. In this study, the remediation efficiency of RL, with or without NBs, was assessed through soil column experiments (soil contaminated with phenanthrene). Through the analysis of the two-site non-equilibrium diffusion model, there was a synergistic effect between NBs and RL. The introduction of NBs led to a reduction of up to 24.3 % in the total removal time of phenanthrene. The direct reason for this was that with NBs, the retardation factor of RL was reduced by 1.9 % to 15.4 %, which accelerated the solute replacement of RL. The reasons for this synergy were multifaceted. Detailed analysis reveals that NBs improve RL's colloidal stability, increase its absolute zeta potential, and reduce its soil adsorption capacity by 13.3 %-19.9 %. Furthermore, NBs and their interaction with RL substantially diminish the surface tension, contact angle, and dynamic viscosity of the leaching solution. These changes in surface thermodynamic and rheological properties significantly enhance the migration efficiency of the eluent. The research outcomes facilitate a thorough comprehension of NBs' attributes and their relevant applications, and propose an eco-friendly method to improve the efficiency of surfactant remediation.
  17. Kasabov N, Scott NM, Tu E, Marks S, Sengupta N, Capecci E, et al.
    Neural Netw, 2016 Jun;78:1-14.
    PMID: 26576468 DOI: 10.1016/j.neunet.2015.09.011
    The paper describes a new type of evolving connectionist systems (ECOS) called evolving spatio-temporal data machines based on neuromorphic, brain-like information processing principles (eSTDM). These are multi-modular computer systems designed to deal with large and fast spatio/spectro temporal data using spiking neural networks (SNN) as major processing modules. ECOS and eSTDM in particular can learn incrementally from data streams, can include 'on the fly' new input variables, new output class labels or regression outputs, can continuously adapt their structure and functionality, can be visualised and interpreted for new knowledge discovery and for a better understanding of the data and the processes that generated it. eSTDM can be used for early event prediction due to the ability of the SNN to spike early, before whole input vectors (they were trained on) are presented. A framework for building eSTDM called NeuCube along with a design methodology for building eSTDM using this is presented. The implementation of this framework in MATLAB, Java, and PyNN (Python) is presented. The latter facilitates the use of neuromorphic hardware platforms to run the eSTDM. Selected examples are given of eSTDM for pattern recognition and early event prediction on EEG data, fMRI data, multisensory seismic data, ecological data, climate data, audio-visual data. Future directions are discussed, including extension of the NeuCube framework for building neurogenetic eSTDM and also new applications of eSTDM.
  18. Zandi K, Bassit L, Amblard F, Cox BD, Hassandarvish P, Moghaddam E, et al.
    PMID: 31061163 DOI: 10.1128/AAC.00397-19
    Dengue virus (DENV) and Japanese encephalitis virus (JEV) are important arthropod-borne viruses from the Flaviviridae family. DENV is a global public health problem with significant social and economic impacts, especially in tropical and subtropical areas. JEV is a neurotropic arbovirus endemic to east and southeast Asia. There are no U.S. FDA-approved antiviral drugs available to treat or to prevent DENV and JEV infections, leaving nearly one-third of the world's population at risk for infection. Therefore, it is crucial to discover potent antiviral agents against these viruses. Nucleoside analogs, as a class, are widely used for the treatment of viral infections. In this study, we discovered nucleoside analogs that possess potent and selective anti-JEV and anti-DENV activities across all serotypes in cell-based assay systems. Both viruses were susceptible to sugar-substituted 2'-C-methyl analogs with either cytosine or 7-deaza-7-fluoro-adenine nucleobases. Mouse studies confirmed the anti-DENV activity of these nucleoside analogs. Molecular models were assembled for DENV serotype 2 (DENV-2) and JEV RNA-dependent RNA polymerase replication complexes bound to nucleotide inhibitors. These models show similarities between JEV and DENV-2, which recognize the same nucleotide inhibitors. Collectively, our findings provide promising compounds and a structural rationale for the development of direct-acting antiviral agents with dual activity against JEV and DENV infections.
  19. Calleja N, AbdAllah A, Abad N, Ahmed N, Albarracin D, Altieri E, et al.
    JMIR Infodemiology, 2021 09 15;1(1):e30979.
    PMID: 34604708 DOI: 10.2196/30979
    Background: An infodemic is an overflow of information of varying quality that surges across digital and physical environments during an acute public health event. It leads to confusion, risk-taking, and behaviors that can harm health and lead to erosion of trust in health authorities and public health responses. Owing to the global scale and high stakes of the health emergency, responding to the infodemic related to the pandemic is particularly urgent. Building on diverse research disciplines and expanding the discipline of infodemiology, more evidence-based interventions are needed to design infodemic management interventions and tools and implement them by health emergency responders.

    Objective: The World Health Organization organized the first global infodemiology conference, entirely online, during June and July 2020, with a follow-up process from August to October 2020, to review current multidisciplinary evidence, interventions, and practices that can be applied to the COVID-19 infodemic response. This resulted in the creation of a public health research agenda for managing infodemics.

    Methods: As part of the conference, a structured expert judgment synthesis method was used to formulate a public health research agenda. A total of 110 participants represented diverse scientific disciplines from over 35 countries and global public health implementing partners. The conference used a laddered discussion sprint methodology by rotating participant teams, and a managed follow-up process was used to assemble a research agenda based on the discussion and structured expert feedback. This resulted in a five-workstream frame of the research agenda for infodemic management and 166 suggested research questions. The participants then ranked the questions for feasibility and expected public health impact. The expert consensus was summarized in a public health research agenda that included a list of priority research questions.

    Results: The public health research agenda for infodemic management has five workstreams: (1) measuring and continuously monitoring the impact of infodemics during health emergencies; (2) detecting signals and understanding the spread and risk of infodemics; (3) responding and deploying interventions that mitigate and protect against infodemics and their harmful effects; (4) evaluating infodemic interventions and strengthening the resilience of individuals and communities to infodemics; and (5) promoting the development, adaptation, and application of interventions and toolkits for infodemic management. Each workstream identifies research questions and highlights 49 high priority research questions.

    Conclusions: Public health authorities need to develop, validate, implement, and adapt tools and interventions for managing infodemics in acute public health events in ways that are appropriate for their countries and contexts. Infodemiology provides a scientific foundation to make this possible. This research agenda proposes a structured framework for targeted investment for the scientific community, policy makers, implementing organizations, and other stakeholders to consider.

  20. Global Burden of Disease 2019 Cancer Collaboration, Kocarnik JM, Compton K, Dean FE, Fu W, Gaw BL, et al.
    JAMA Oncol, 2022 Mar 01;8(3):420-444.
    PMID: 34967848 DOI: 10.1001/jamaoncol.2021.6987
    IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden.

    OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.

    EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs).

    FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles.

    CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

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