Browse publications by year: 2019

  1. Axtner J, Crampton-Platt A, Hörig LA, Mohamed A, Xu CCY, Yu DW, et al.
    Gigascience, 2019 Apr 01;8(4).
    PMID: 30997489 DOI: 10.1093/gigascience/giz029
    BACKGROUND: The use of environmental DNA for species detection via metabarcoding is growing rapidly. We present a co-designed lab workflow and bioinformatic pipeline to mitigate the 2 most important risks of environmental DNA use: sample contamination and taxonomic misassignment. These risks arise from the need for polymerase chain reaction (PCR) amplification to detect the trace amounts of DNA combined with the necessity of using short target regions due to DNA degradation.

    FINDINGS: Our high-throughput workflow minimizes these risks via a 4-step strategy: (i) technical replication with 2 PCR replicates and 2 extraction replicates; (ii) using multi-markers (12S,16S,CytB); (iii) a "twin-tagging," 2-step PCR protocol; and (iv) use of the probabilistic taxonomic assignment method PROTAX, which can account for incomplete reference databases. Because annotation errors in the reference sequences can result in taxonomic misassignment, we supply a protocol for curating sequence datasets. For some taxonomic groups and some markers, curation resulted in >50% of sequences being deleted from public reference databases, owing to (i) limited overlap between our target amplicon and reference sequences, (ii) mislabelling of reference sequences, and (iii) redundancy. Finally, we provide a bioinformatic pipeline to process amplicons and conduct PROTAX assignment and tested it on an invertebrate-derived DNA dataset from 1,532 leeches from Sabah, Malaysia. Twin-tagging allowed us to detect and exclude sequences with non-matching tags. The smallest DNA fragment (16S) amplified most frequently for all samples but was less powerful for discriminating at species rank. Using a stringent and lax acceptance criterion we found 162 (stringent) and 190 (lax) vertebrate detections of 95 (stringent) and 109 (lax) leech samples.

    CONCLUSIONS: Our metabarcoding workflow should help research groups increase the robustness of their results and therefore facilitate wider use of environmental and invertebrate-derived DNA, which is turning into a valuable source of ecological and conservation information on tetrapods.

    MeSH terms: Laboratories; Quality Control; Computational Biology/methods; Databases, Nucleic Acid*; Metagenome*; Metagenomics/methods*; Workflow
  2. Sharma A, Kamble SH, León F, Chear NJ, King TI, Berthold EC, et al.
    Drug Test Anal, 2019 Aug;11(8):1162-1171.
    PMID: 30997725 DOI: 10.1002/dta.2604
    Kratom (Mitragyna speciosa) is a psychoactive plant popular in the United States for the self-treatment of pain and opioid addiction. For standardization and quality control of raw and commercial kratom products, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of ten key alkaloids, namely: corynantheidine, corynoxine, corynoxine B, 7-hydroxymitragynine, isocorynantheidine, mitragynine, mitraphylline, paynantheine, speciociliatine, and speciogynine. Chromatographic separation of diastereomers, or alkaloids sharing same ion transitions, was achieved on an Acquity BEH C18 column with a gradient elution using a mobile phase containing acetonitrile and aqueous ammonium acetate buffer (10mM, pH 3.5). The developed method was linear over a concentration range of 1-200 ng/mL for each alkaloid. The total analysis time per sample was 22.5 minutes. The analytical method was validated for accuracy, precision, robustness, and stability. After successful validation, the method was applied for the quantification of kratom alkaloids in alkaloid-rich fractions, ethanolic extracts, lyophilized teas, and commercial products. Mitragynine (0.7%-38.7% w/w), paynantheine (0.3%-12.8% w/w), speciociliatine (0.4%-12.3% w/w), and speciogynine (0.1%-5.3% w/w) were the major alkaloids in the analyzed kratom products/extracts. Minor kratom alkaloids (corynantheidine, corynoxine, corynoxine B, 7-hydroxymitragynine, isocorynantheidine) were also quantified (0.01%-2.8% w/w) in the analyzed products; however mitraphylline was below the lower limit of quantification in all analyses.
    MeSH terms: Alkaloids/analysis*; Chromatography, High Pressure Liquid/methods; Plant Extracts/chemistry*; Plant Leaves/chemistry*; Mitragyna/chemistry*; Tandem Mass Spectrometry/methods; Limit of Detection
  3. Chen YY, Ahmad M, Ismail FB
    Future Oncol, 2019 May;15(15):1759-1770.
    PMID: 30997858 DOI: 10.2217/fon-2018-0686
    Aim: The present study investigated the relationship between psychological problems, illness acceptance and cancer-related complaints among Malaysian cancer patients. Patients & methods: One hundred and six cancer patients were recruited and were requested to complete validated self-reported questionnaires that measured their psychological distresses, sleep quality, pain, fatigue and illness acceptance. Results: There was a significant relationship between cancer-related symptoms, illness acceptance and psychological distresses commonly experienced by local cancer patients (p < 0.05). Illness acceptance was shown to be a mediator of cancer-related complaints and psychological distresses. Conclusion: Malaysian cancer patients with more cancer-related complaints reported a higher level of psychological distresses and poorer illness acceptance. Increased level of illness acceptance was suggested in managing cancer patients with psychological distresses and cancer-related complaints.
    MeSH terms: Adaptation, Psychological*; Adult; Aged; Aged, 80 and over; Fatigue; Female; Humans; Malaysia/epidemiology; Male; Middle Aged; Neoplasms/epidemiology*; Neoplasms/psychology*; Pain; Surveys and Questionnaires; Sleep; Stress, Psychological*; Public Health Surveillance
  4. Birn AE, Brown TM
    Am J Public Health, 2019 Apr 18.
    PMID: 30998404 DOI: 10.2105/AJPH.2019.305065
    Elizabeth Fee was a remarkable and influential public health historian, whose personal and professional trajectories led her to speak truth to and about power in public health, past and present. Born in Northern Ireland in 1946 to Irish-Methodist missionary parents, Liz's childhood brought her into contact with peoples and struggles across the globe. At just five weeks of age, she was whisked away by her parents to civil war-era China, where she lost hearing in one ear from an untreated bout with scarlet fever. In midchildhood, she attended school in Malaysia, after which her family returned to Belfast. There, she came of age amid festering political and religious violence, learning firsthand that history is told and retold by protagonists and witnesses, oppressors and oppressed. (Am J Public Health. Published online ahead of print April 18, 2019: e1-e4. doi:10.2105/AJPH.2019.305065).
    MeSH terms: China; Female; Hearing Tests; Humans; Malaysia; Northern Ireland; Parents; Public Health; Scarlet Fever; Violence; Protestantism; Missionaries
  5. Pare R, Soon PS, Shah A, Lee CS
    PLoS One, 2019;14(4):e0214604.
    PMID: 30998679 DOI: 10.1371/journal.pone.0214604
    Breast cancer is a heterogeneous disease displaying different histopathological characteristics, molecular profiling and clinical behavior. This study describes the expression patterns of senescence markers P53, DEC1 and DCR2 and assesses their significance on patient survival as a single or combined marker with P16 or P14 using breast cancer progression series. One thousand and eighty (1080) patients with primary invasive ductal carcinoma, no special type, were recruited through an 11-year retrospective study period. We constructed tissue microarrays of normal, benign hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma from each patient and performed immunohistochemical staining to study the protein expression. Statistical analysis includes Pearson chi-square, Kaplan-Meier log ran test and Cox proportional hazard regression were undertaken to determine the associations and predict the survival outcomes. P53, DEC1 and DCR2 expression correlated significantly with normal, benign, premalignant and malignant tissues with (p<0.05). The expression profile of these genes increases from normal to benign to premalignant and plateaued from premalignant to malignant phenotype. There is a significant association between P53 protein expression and age, grade, staging, lymphovascular invasion, estrogen receptor, progesterone receptor and HER2 whereas DCR2 protein expression significantly correlated with tumour grade, hormone receptors status and HER2 (p<0.05 respectively). P53 overexpression correlated with increased risk of relapse (p = 0.002) specifically in patients who did not receive hormone therapy (p = 0.005) or chemotherapy (p<0.0001). The combination of P53+/P16+ is significantly correlated with poor overall and disease-free survival, whereas a combination of P53+/P14+ is associated with worse outcome in disease-free survival (p<0.05 respectively). P53 overexpression appears to be a univariate predictor of poor disease-free survival. The expression profiles of DEC1 and DCR2 do not appear to correlate with patient survival outcomes. The combination of P53 with P16, rather P53 expression alone, appears to provide more useful clinical information on patient survival outcomes in breast cancer.
    MeSH terms: Aged; Breast Neoplasms/mortality; Breast Neoplasms/pathology*; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Retrospective Studies; Biomarkers, Tumor/metabolism*; Proportional Hazards Models; Tumor Suppressor Protein p53/metabolism; Disease-Free Survival; Receptor, ErbB-2/metabolism; Cyclin-Dependent Kinase Inhibitor p16/metabolism; Tumor Suppressor Proteins/metabolism; Kaplan-Meier Estimate; Tumor Necrosis Factor Decoy Receptors/metabolism
  6. Atari M, Afhami R, Swami V
    PLoS One, 2019;14(4):e0215202.
    PMID: 30998716 DOI: 10.1371/journal.pone.0215202
    Several self-report measures of conspiracist beliefs have been developed in Western populations, but examination of their psychometric properties outside Europe and North America is limited. This study aimed to examine the psychometric properties of three widely-used measures of conspiracist beliefs in Iran. We translated the Belief in Conspiracy Theory Inventory (BCTI), Conspiracy Mentality Questionnaire (CMQ), and Generic Conspiracist Belief Scale (GCBS) into Persian. Factorial validity was examined using principal-axis factor analysis in a community sample from Tehran, Iran (N = 544). Further, the relationships between scores on these measures and hypothesized antecedents (i.e., education, schizotypal personality, information processing style, superstitious beliefs, religiosity, and political orientation) were examined. Overall, we failed to find support for the parent factor structures of two of the three scales (BCTI and GCBS) and evidence of construct validity for all three scales was limited. These results highlight the necessity of further psychometric work on existing measures of conspiracy theories in diverse culturo-linguistic groups and the development of context-specific measures of conspiracist beliefs.
    MeSH terms: Adolescent; Adult; Aged; Cognition*; Female; Humans; Iran; Male; Middle Aged; Personality*; Psychometrics; Surveys and Questionnaires*; Translations*
  7. Rahman N'A, Chan CM, Zakaria MI, Jaafar MJ
    Australas Emerg Care, 2019 Mar;22(1):13-21.
    PMID: 30998867 DOI: 10.1016/j.auec.2018.11.002
    INTRODUCTION: An emergency department (ED) is often the first point of medical contact for sepsis patient, which plays an important role in early identification and management of high-risk septic patients. The present study was aim to evaluate emergency personnel's knowledge and attitude toward identification and management of systemic inflammatory response syndrome (SIRS) and sepsis.

    METHODS: This cross-sectional study was conducted in a tertiary teaching hospital and recruited all emergency personnel. A validated questionnaire on knowledge and attitude towards identification and management of SIRS/sepsis was distributed among 120 emergency personnel. Data were analyzed using descriptive and inferential statistics.

    RESULTS: Overall finding founds emergency nurses and assistant medical officer appeared to have moderate knowledge in several important areas of SIRS/sepsis identification and management. Majority of the emergency personnel have neutral attitudes, as they do not give enough importance towards identification of patients with SIRS and sepsis. The present study finding found that knowledge of clinical criteria and management of SIRS/sepsis was highest among assistant medical officers (p=0.02) and bachelor's degree holders (p=0.02) with emergency experience more than 5 years (p=0.03). A trend toward an increase in knowledge of SIRS and sepsis is significantly correlated with positive attitudes.

    CONCLUSION: The emergency personnel demonstrated a moderate knowledge and neutral attitude toward identification and management of SIRS and sepsis. Therefore, the awareness and knowledge of SIRS and sepsis should be enhanced among emergency personnel in order to improve outcome.

    MeSH terms: Adult; Analysis of Variance; Cross-Sectional Studies; Female; Humans; Health Knowledge, Attitudes, Practice*; Malaysia; Male; Surveys and Questionnaires; Systemic Inflammatory Response Syndrome/diagnosis; Systemic Inflammatory Response Syndrome/physiopathology; Systemic Inflammatory Response Syndrome/psychology*; Sepsis/diagnosis; Sepsis/physiopathology; Sepsis/psychology*; Tertiary Care Centers/organization & administration
  8. Leong MC, Ahmed Alhassan AA, Sivalingam S, Alwi M
    Ann Thorac Surg, 2019 09;108(3):813-819.
    PMID: 30998905 DOI: 10.1016/j.athoracsur.2019.03.045
    BACKGROUND: Ductal stenting is performed to retrain involuted left ventricles (LVs) in patients with d-transposition of the great arteries and intact ventricular septum (TGA-IVS). However, its efficacy is largely unknown. This study aimed to determine the safety and efficacy of ductal stenting in retraining of the involuted LV in patients with TGA-IVS.

    METHODS: This was a single-center, retrospective study. Echocardiographic assessment of the LV geometry, mass, and free wall thickness was performed before stenting and before the arterial switch operation. Patients then underwent the arterial switch operation, and the postoperative outcomes were reviewed.

    RESULTS: There were 11 consecutive patients (male, 81.8%; mean age at stenting, 43.11 ± 18.19 days) with TGA-IVS with involuted LV who underwent LV retraining by ductal stenting from July 2013 to December 2017. Retraining by ductus stenting failed in 4 patients (36.3%). Two patients required pulmonary artery banding, and another 2 had an LV mass index of less than 35 g/m2. Patients in the successful group had improved LV mass index from 45.14 ± 17.91 to 81.86 ± 33.11g/m2 (p = 0.023) compared with 34.50 ± 10.47 to 20.50 ± 9.88 g/m2 (p = 0.169) and improved LV geometry after ductal stenting. The failed group was associated with an increased need for extracorporeal support (14.5% vs 50%, p = 0.012). An atrial septal defect-to-interatrial septum length ratio of more than 0.38 was associated with failed LV retraining.

    CONCLUSIONS: Ductal stenting is an effective method to retrain the involuted LV in TGA-IVS. A large atrial septal defect (atrial septal defect-to-interatrial septum length ratio >0.38) was associated with poor response to LV retraining.

    MeSH terms: Academic Medical Centers; Arterial Switch Operation/methods*; Ductus Arteriosus/surgery; Echocardiography/methods; Female; Follow-Up Studies; Heart Septal Defects, Atrial/surgery*; Heart Ventricles/surgery; Humans; Infant, Newborn; Malaysia; Male; Retrospective Studies; Transposition of Great Vessels/mortality; Transposition of Great Vessels/surgery*; Cohort Studies; Stents*; Survival Analysis; Ventricular Function, Left/physiology*; Risk Assessment; Patient Safety
  9. Wong ML, Ahmed MA, Sulaiman WYW, Manin BO, Leong CS, Quan FS, et al.
    Infect Genet Evol, 2019 09;73:26-32.
    PMID: 30999059 DOI: 10.1016/j.meegid.2019.04.010
    We explored and constructed haplotype network for simian malaria species: Plasmodium knowlesi, P. cynomolgi and P. inui aiming to understand the transmission dynamics between mosquitoes, humans and macaques. Mosquitoes were collected from villages in an area where zoonotic malaria is prevalent. PCR analysis confirmed Anopheles balabacensis as the main vector for macaque parasites, moreover nearly 60% of the mosquitoes harboured more than one Plasmodium species. Fragments of the A-type small subunit ribosomal RNA (SS rRNA) amplified from salivary gland sporozoites, and equivalent sequences obtained from GenBank were used to construct haplotype networks. The patterns were consistent with the presence of geographically distinct populations for P. inui and P. cynomolgi, and with three discrete P. knowlesi populations. This study provides a preliminary snapshot of the structure of these populations, that was insufficient to answer our aim. Thus, collection of parasites from their various hosts and over time, associated with a systematic analysis of a set of genetical loci is strongly advocated in order to obtain a clear picture of the parasite population and the flow between different hosts. This is important to devise measures that will minimise the risk of transmission to humans, because zoonotic malaria impedes malaria elimination.
    MeSH terms: Animals; Anopheles; Disease Vectors; Haplotypes; Humans; Macaca; Malaria; Parasites; RNA; RNA, Ribosomal; Salivary Glands; Polymerase Chain Reaction; Plasmodium knowlesi; Databases, Nucleic Acid; Sporozoites; Ribosome Subunits, Small
  10. Tan CH, Show PL, Ling TC, Nagarajan D, Lee DJ, Chen WH, et al.
    Bioresour Technol, 2019 Aug;285:121331.
    PMID: 30999192 DOI: 10.1016/j.biortech.2019.121331
    Third generation biofuels, also known as microalgal biofuels, are promising alternatives to fossil fuels. One attractive option is microalgal biodiesel as a replacement for diesel fuel. Chlamydomonas sp. Tai-03 was previously optimized for maximal lipid production for biodiesel generation, achieving biomass growth and productivity of 3.48 ± 0.04 g/L and 0.43 ± 0.01 g/L/d, with lipid content and productivity of 28.6 ± 1.41% and 124.1 ± 7.57 mg/L/d. In this study, further optimization using 5% CO2 concentration and semi-batch operation with 25% medium replacement ratio, enhanced the biomass growth and productivity to 4.15 ± 0.12 g/L and 1.23 ± 0.02 g/L/d, with lipid content and productivity of 19.4 ± 2.0% and 239.6 ± 24.8 mg/L/d. The major fatty acid methyl esters (FAMEs) were palmitic acid (C16:0), oleic acid (C18:1), and linoleic acid (C18:2). These short-chain FAMEs combined with high growth make Chlamydomonas sp. Tai-03 a suitable candidate for biodiesel synthesis.
    MeSH terms: Biological Phenomena; Carbon Dioxide; Chlamydomonas; Esters; Fatty Acids; Fatty Acids, Volatile; Fossil Fuels; Gasoline; Biomass; Oleic Acid; Palmitic Acid; Linoleic Acid; Biofuels; Microalgae
  11. Roselin LS, Juang RS, Hsieh CT, Sagadevan S, Umar A, Selvin R, et al.
    Materials (Basel), 2019 Apr 15;12(8).
    PMID: 30991665 DOI: 10.3390/ma12081229
    Rechargeable batteries are attractive power storage equipment for a broad diversity of applications. Lithium-ion (Li-ion) batteries are widely used the superior rechargeable battery in portable electronics. The increasing needs in portable electronic devices require improved Li-ion batteries with excellent results over many discharge-recharge cycles. One important approach to ensure the electrodes' integrity is by increasing the storage capacity of cathode and anode materials. This could be achieved using nanoscale-sized electrode materials. In the article, we review the recent advances and perspectives of carbon nanomaterials as anode material for Lithium-ion battery applications. The first section of the review presents the general introduction, industrial use, and working principles of Li-ion batteries. It also demonstrates the advantages and disadvantages of nanomaterials and challenges to utilize nanomaterials for Li-ion battery applications. The second section of the review describes the utilization of various carbon-based nanomaterials as anode materials for Li-ion battery applications. The last section presents the conclusion and future directions.
  12. Lim CC, Choong YS, Lim TS
    Int J Mol Sci, 2019 Apr 15;20(8).
    PMID: 30991723 DOI: 10.3390/ijms20081861
    Antibodies leverage on their unique architecture to bind with an array of antigens. The strength of interaction has a direct relation to the affinity of the antibodies towards the antigen. In vivo affinity maturation is performed through multiple rounds of somatic hypermutation and selection in the germinal centre. This unique process involves intricate sequence rearrangements at the gene level via molecular mechanisms. The emergence of in vitro display technologies, mainly phage display and recombinant DNA technology, has helped revolutionize the way antibody improvements are being carried out in the laboratory. The adaptation of molecular approaches in vitro to replicate the in vivo processes has allowed for improvements in the way recombinant antibodies are designed and tuned. Combinatorial libraries, consisting of a myriad of possible antibodies, are capable of replicating the diversity of the natural human antibody repertoire. The isolation of target-specific antibodies with specific affinity characteristics can also be accomplished through modification of stringent protocols. Despite the ability to screen and select for high-affinity binders, some 'fine tuning' may be required to enhance antibody binding in terms of its affinity. This review will provide a brief account of phage display technology used for antibody generation followed by a summary of different combinatorial library characteristics. The review will focus on available strategies, which include molecular approaches, next generation sequencing, and in silico approaches used for antibody affinity maturation in both therapeutic and diagnostic applications.
    MeSH terms: Animals; Antibodies, Monoclonal/genetics*; Antibodies, Monoclonal/immunology; Antibodies, Monoclonal/chemistry; Antibody Affinity; Humans; Immunoglobulin G/genetics; Immunoglobulin G/immunology; Immunoglobulin G/chemistry; Mutagenesis; Peptide Library; High-Throughput Nucleotide Sequencing/methods*; Cell Surface Display Techniques/methods*
  13. Othman A, Goggin KA, Tahir NI, Brodrick E, Singh R, Sambanthamurthi R, et al.
    BMC Res Notes, 2019 Apr 16;12(1):229.
    PMID: 30992056 DOI: 10.1186/s13104-019-4263-7
    OBJECTIVE: The addition of residual oils such as palm fibre oil (PFO) and sludge palm oil (SPO) to crude palm oil (CPO) can be problematic within supply chains. PFO is thought to aggravate the accumulation of monochloropropanediols (MCPDs) in CPO, whilst SPO is an acidic by-product of CPO milling and is not fit for human consumption. Traditional targeted techniques to detect such additives are costly, time-consuming and require highly trained operators. Therefore, we seek to assess the use of gas chromatography-ion mobility spectrometry (GC-IMS) for rapid, cost-effective screening of CPO for the presence of characteristic PFO and SPO volatile organic compound (VOC) fingerprints.

    RESULTS: Lab-pressed CPO and commercial dispatch tank (DT) CPO were spiked with PFO and SPO, respectively. Both additives were detectable at concentrations of 1% and 10% (w/w) in spiked lab-pressed CPO, via seven PFO-associated VOCs and 21 SPO-associated VOCs. DT controls could not be distinguished from PFO-spiked DT CPO, suggesting these samples may have already contained low levels of PFO. DT controls were free of SPO. SPO was detected in all SPO-spiked dispatch tank samples by all 21 of the previously distinguished VOCs and had a significant fingerprint consisting of four spectral regions.

    MeSH terms: Food Analysis/instrumentation; Food Analysis/methods*; Food Contamination/analysis*; Humans; Gas Chromatography-Mass Spectrometry; Complex Mixtures/chemistry*; Volatile Organic Compounds/classification; Volatile Organic Compounds/isolation & purification*
  14. Zhang XC, Wang J, Shao GG, Wang Q, Qu X, Wang B, et al.
    Nat Commun, 2019 04 16;10(1):1772.
    PMID: 30992440 DOI: 10.1038/s41467-019-09762-1
    Deep understanding of the genomic and immunological differences between Chinese and Western lung cancer patients is of great importance for target therapy selection and development for Chinese patients. Here we report an extensive molecular and immune profiling study of 245 Chinese patients with non-small cell lung cancer. Tumor-infiltrating lymphocyte estimated using immune cell signatures is found to be significantly higher in adenocarcinoma (ADC, 72.5%) compared with squamous cell carcinoma (SQCC, 54.4%). The correlation of genomic alterations with immune signatures reveals that low immune infiltration was associated with EGFR mutations in ADC samples, PI3K and/or WNT pathway activation in SQCC. While KRAS mutations are found to be significantly associated with T cell infiltration in ADC samples. The SQCC patients with high antigen presentation machinery and cytotoxic T cell signature scores are found to have a prolonged overall survival time.
    MeSH terms: Aged; Carcinoma, Non-Small-Cell Lung/genetics*; Carcinoma, Non-Small-Cell Lung/immunology; Carcinoma, Non-Small-Cell Lung/mortality; Carcinoma, Squamous Cell/genetics*; Carcinoma, Squamous Cell/immunology; Carcinoma, Squamous Cell/mortality; Female; Humans; Lung Neoplasms/genetics*; Lung Neoplasms/immunology; Male; Middle Aged; Mutation; T-Lymphocytes, Cytotoxic/immunology; Lymphocytes, Tumor-Infiltrating/immunology; Proto-Oncogene Proteins p21(ras)/genetics; Antigen Presentation/genetics; Antigen Presentation/immunology; Genomics; Asian Continental Ancestry Group/genetics*; Wnt Signaling Pathway/genetics; Wnt Signaling Pathway/immunology; ErbB Receptors/genetics; Datasets as Topic
  15. Chaisson MJP, Sanders AD, Zhao X, Malhotra A, Porubsky D, Rausch T, et al.
    Nat Commun, 2019 04 16;10(1):1784.
    PMID: 30992455 DOI: 10.1038/s41467-018-08148-z
    The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per genome. We also discover 156 inversions per genome and 58 of the inversions intersect with the critical regions of recurrent microdeletion and microduplication syndromes. Taken together, our SV callsets represent a three to sevenfold increase in SV detection compared to most standard high-throughput sequencing studies, including those from the 1000 Genomes Project. The methods and the dataset presented serve as a gold standard for the scientific community allowing us to make recommendations for maximizing structural variation sensitivity for future genome sequencing studies.
    MeSH terms: Algorithms; Chromosome Mapping/methods; Haplotypes/genetics*; Humans; Genome, Human/genetics*; Genomics/methods*; Databases, Genetic; INDEL Mutation; Genomic Structural Variation*; High-Throughput Nucleotide Sequencing/methods
  16. Waid JL, Sinharoy SS, Ali M, Stormer AE, Thilsted SH, Gabrysch S
    Curr Dev Nutr, 2019 Apr;3(4):nzy091.
    PMID: 30993255 DOI: 10.1093/cdn/nzy091
    BACKGROUND: The government of Bangladesh has implemented multiple policies since 1971 to provide the population with more diverse and nutritious diets.

    OBJECTIVE: The aim of this study was to examine the drivers of dietary change over time and the roles agriculture and economic development have played.

    METHODS: We used principal component analysis to derive dietary patterns from 7 cross-sectional rounds of the Bangladesh Household [Income and] Expenditure Survey. We then used linear probability models to estimate associations of adherence to dietary patterns with socio-economic characteristics of households, and with agricultural production on the household and regional level. For dietary patterns that increased or decreased over time, Blinder-Oaxaca decomposition was used to assess factors associated with these changes.

    RESULTS: Seven dietary patterns were identified: modern, traditional, festival, winter, summer, monotonous, and spices. All diets were present in all survey rounds. In 1985, over 40% of households had diets not associated with any identified pattern, which declined to 12% by 2010. The proportion of the population in households adhering to the modern, winter, summer, and monotonous diets increased over time, whereas the proportion adhering to the traditional diet decreased. Although many factors were associated with adherence to dietary patterns in the pooled sample, changes in observed factors only explained a limited proportion of change over time due to variation in coefficients between periods. Increased real per capita expenditure was the largest driver of elevated adherence to dietary patterns over time, whereas changes in the agricultural system increased adherence to less diverse dietary patterns.

    CONCLUSIONS: These findings highlight the need for both diversified agricultural production and a continued reduction in poverty in order to drive dietary improvement. This study lays the groundwork for further analysis of the impact of changing diets on health and nutrition.

  17. Sheshala R, Anuar NK, Abu Samah NH, Wong TW
    AAPS PharmSciTech, 2019 Apr 15;20(5):164.
    PMID: 30993407 DOI: 10.1208/s12249-019-1362-7
    This review highlights in vitro drug dissolution/permeation methods available for topical and transdermal nanocarriers that have been designed to modulate the propensity of drug release, drug penetration into skin, and permeation into systemic circulation. Presently, a few of USFDA-approved in vitro dissolution/permeation methods are available for skin product testing with no specific application to nanocarriers. Researchers are largely utilizing the in-house dissolution/permeation testing methods of nanocarriers. These drug release and permeation methods are pending to be standardized. Their biorelevance with reference to in vivo plasma concentration-time profiles requires further exploration to enable translation of in vitro data for in vivo or clinical performance prediction.
    MeSH terms: Administration, Cutaneous*; Animals; Drug Carriers*; Humans; Permeability; Skin Absorption*; Solubility; Nanostructures*; Drug Liberation
  18. Ramli R, Oxley JA
    Traffic Inj Prev, 2019;20(3):332-335.
    PMID: 30995129 DOI: 10.1080/15389588.2018.1557640
    Objectives: We encountered an unusual facial laceration wound in relation to motorcycle helmet visor use during our clinical practice. We aimed to assess the prevalence of this unusual facial injury among motorcyclists who sustained facial injuries in selected hospitals and to determine the possible mechanism involved. Methods: We used our prospective cross-sectional substudy involving injured motorcyclists presenting at major trauma hospitals in Southern Klang Valley, Malaysia, between March 2010 and March 2011. of 391 subjects with facial injuries, 2 male motorcyclists sustained this laceration. The wounds were assessed and we believed that each was associated with the helmet visor. One of the visors was collected and the edge was inspected using scanning electron microscopy (SEM). Results: The prevalence of this unusual injury was 0.51% (95% confidence interval, 0.002-0.012) among motorcyclists who sustained facial injuries. Both cases were involved in a head-on collision with their colliding partners and their helmets were intact throughout the crash. The visor in case 1 was intact, but the visor in case 2 was broken. SEM analysis showed that the visor in case 1 had a potential cutting surface. We postulated that with helmet rotation in the forward and downward position and with some degree of visor bending or with a dislodged visor, the sharp-edged visor could potentially severely lacerate the face. Conclusion: This injury affects facial aesthetics and early referral to the facial surgery team is advocated. Documentation of the mechanism of injury, the patient's helmet and visor is obligatory, so that this information can be delivered to the regional road safety authority for preventive measures.
    MeSH terms: Cross-Sectional Studies; Documentation; Esthetics; Face; Facial Injuries; Head Protective Devices; Humans; Malaysia; Male; Microscopy, Electron, Scanning; Motorcycles; Prospective Studies; Referral and Consultation; Rotation; Prevalence; Lacerations
  19. Hasan H, Abd Rahim MH, Campbell L, Carter D, Abbas A, Montoya A
    N Biotechnol, 2019 Sep 25;52:19-24.
    PMID: 30995533 DOI: 10.1016/j.nbt.2019.04.003
    Lovastatin is widely prescribed to reduce elevated levels of cholesterol and prevent heart-related diseases. Cultivation of Aspergillus terreus (ATCC 20542) with carbohydrates or low-value feedstocks such as glycerol produces lovastatin as a secondary metabolite and (+)-geodin as a by-product. An A. terreus mutant strain was developed (gedCΔ) with a disrupted (+)-geodin biosynthesis pathway. The gedCΔ mutant was created by inserting the antibiotic marker hygromycin B (hyg) within the gedC gene that encodes emodin anthrone polyketide synthase (PKS), a primary gene responsible for initiating (+)-geodin biosynthesis. The effects of emodin anthrone PKS gene disruption on (+)-geodin and lovastatin biosynthesis and the production of the precursors acetyl-CoA and malonyl-CoA were investigated with cultures based on glycerol alone and in combination with lactose. The gedCΔ strain showed improved lovastatin production, particularly when cultivated on the glycerol-lactose mixture, increasing lovastatin production by 80% (113 mg/L) while simultaneously inhibiting (+)-geodin biosynthesis compared to the wild-type strain. This study thus shows that suppression of the (+)-geodin pathway increases lovastatin yield and demonstrates a practical approach of manipulating carbon flux by modulating enzyme activity.
    MeSH terms: Acetyl Coenzyme A/biosynthesis; Aspergillus/metabolism*; Benzofurans/metabolism*; Glycerol/metabolism; Lactose/metabolism; Lovastatin/biosynthesis*; Malonyl Coenzyme A/biosynthesis; Biosynthetic Pathways*
  20. Khoo HE, Ng HS, Yap WS, Goh HJH, Yim HS
    Antioxidants (Basel), 2019 Apr 02;8(4).
    PMID: 30986936 DOI: 10.3390/antiox8040085
    The risk of macular degeneration can be reduced through the consumption of antioxidant-rich foods, supplements, and nutraceutical formulas. This review focuses on the antioxidants, vitamins, and minerals that have been reported for reducing the risk of macular degeneration and other eye-related diseases. Antioxidants including anthocyanins, carotenoids, flavonoids, and vitamins have been shown to reduce the risk of eye-related diseases. Anthocyanins extracted from berries are powerful antioxidants. Cyanidin, delphinidin, malvidin, pelargonidin, peonidin, and petunidin are anthocyanin aglycones detected in berries, currants, and other colored fruits and vegetables. β-Carotene, as well as xanthophyll lutein and zeaxanthin, have been reported to reduce the risk of macular degeneration. Flavonoids from plants help in the prevention of eye-related diseases through anti-inflammatory mechanisms. A combination of these antioxidants, vitamins, and minerals possess a synergistic effect on the prevention or risk reduction of macular degeneration. Formulas have been developed as dietary supplements to cater to the high demand from consumers and patients with eye problems. Many of the formulated dietary supplements that are sold in the market have been clinically proven for their efficacy to treat eye diseases. Although the bioactivities in the supplement capsules or tablets have been scientifically established for reducing risks of several diseases, which include macular degeneration and other eye-related diseases, knowledge on the right dosage, efficacy, and bioavailability of antioxidants, vitamins, and minerals is important for consumers. The information may help them make the best decision in choosing the right dietary supplements and nutraceuticals following the evidence-based recommended dosages and reference intakes for improving general health and preventing eye-related diseases. This review covers the potential causal factors involved in eye diseases, clinically proven treatments, and controversial findings on the antioxidants in the prevention of macular degeneration. Future studies should consider multiethnic and multicenter trials for eliminating potential bias in research.
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