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1. Fulltext Effect of surgical intraocular pressure lowering on retinal structures - nerve fibre layer, foveal avascular zone, peripapillary and macular vessel density: 1 year results

   Ch'ng TW, Gillmann K, Hoskens K, Rao HL, Mermoud A, Mansouri K

   Eye (Lond), 2020 03;34(3):562-571.

   PMID: 31409906 DOI: 10.1038/s41433-019-0560-6

   Abstract

   OBJECTIVES: To determine the effect of surgical intraocular pressure (IOP) lowering on peripapillary retinal nerve fibre layer thickness (RNFL), fovea avascular zone (FAZ), peripapillary and macular vessel density (VD) in glaucoma using with optical coherence tomography angiography (OCT-A).

   METHODS: This was a prospective observational study performed at the Glaucoma Research Centre, Montchoisi Clinic, Lausanne. In total 40 eyes with open-angle glaucoma were included. OCT-A scans were performed before glaucoma surgery, and at 1-month, 3-month, 6-month, and 12-month post-operatively. AngioVue AngioAnalytic (Optovue Inc, Fremont, CA) software was used to analyse the RNFL, FAZ, peripapillary and macular VD. Changes were analysed using analysis of variance (ANOVA) models.

   RESULTS: Mean IOP dropped from 19.4 (±7.0) mmHg pre-surgery and stabilized at 13.0 (±3.1) mmHg at 12 months (p 

   MeSH terms: Humans; Intraocular Pressure; Nerve Fibers; Tomography, Optical Coherence
2. Fulltext BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration

   Loveridge CJ, Slater S, Campbell KJ, Nam NA, Knight J, Ahmad I, et al.

   Oncogene, 2020 02;39(8):1797-1806.

   PMID: 31740786 DOI: 10.1038/s41388-019-1106-x

   Abstract

   BRF1 is a rate-limiting factor for RNA Polymerase III-mediated transcription and is elevated in numerous cancers. Here, we report that elevated levels of BRF1 associate with poor prognosis in human prostate cancer. In vitro studies in human prostate cancer cell lines demonstrated that transient overexpression of BRF1 increased cell proliferation whereas the transient downregulation of BRF1 reduced proliferation and mediated cell cycle arrest. Consistent with our clinical observations, BRF1 overexpression in a Pten-deficient mouse (PtenΔ/Δ BRF1Tg) prostate cancer model accelerated prostate carcinogenesis and shortened survival. In PtenΔ/Δ BRF1Tg tumours, immune and inflammatory processes were altered, with reduced tumoral infiltration of neutrophils and CD4 positive T cells, which can be explained by decreased levels of complement factor D (CFD) and C7 components of the complement cascade, an innate immune pathway that influences the adaptive immune response. We tested if the secretome was involved in BRF1-driven tumorigenesis. Unbiased proteomic analysis on BRF1-overexpresing PC3 cells confirmed reduced levels of CFD in the secretome, implicating the complement system in prostate carcinogenesis. We further identify that expression of C7 significantly correlates with expression of CD4 and has the potential to alter clinical outcome in human prostate cancer, where low levels of C7 associate with poorer prognosis.

   MeSH terms: Aged; Cell Cycle; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms/diagnosis; Prostatic Neoplasms/immunology*; Prostatic Neoplasms/metabolism; Prostatic Neoplasms/pathology*; CD4-Positive T-Lymphocytes/immunology; TATA-Binding Protein Associated Factors/metabolism*; Cell Proliferation; PTEN Phosphohydrolase/metabolism; Carcinogenesis*
3. Molecular Prevalence and Epidemiology of Trypanosoma evansi Among Cattle in Peninsular Malaysia

   Ola-Fadunsin SD, Gimba FI, Abdullah DA, Abdullah FJF, Sani RA

   Acta Parasitol, 2020 Mar;65(1):165-173.

   PMID: 31797192 DOI: 10.2478/s11686-019-00150-9

   Abstract

   BACKGROUND: Animal trypanosomiasis (Surra) caused by Trypanosoma evansi (T. evansi) is known to be one of the important haemoprotozoan parasites that causes great economical loss on animal production due to mortality and loss of condition.

   METHODS: A cross-sectional study was designed to evaluate the prevalence and risk factors associated with T. evansi infection among cattle in Peninsular Malaysia. Polymerase chain reaction (PCR) was employed on 1045 blood samples collected from 43 farms. A well-structured questionnaire was used to collect data on risk factors associated with T. evansi prevalence. The RoTat 1.2 set of primers was used to amplify products of 205 base pair.

   RESULTS: The overall prevalence was found to be 17.9% (187/1045; 95% CI = 15.66-20.31). Trypanosoma evansi was detected among cattle in all the States of Peninsular Malaysia. Breeds of cattle and closeness to waste area, where the risk factors significantly (p 

   MeSH terms: Animals; Cattle; Cattle Diseases/epidemiology*; Cattle Diseases/parasitology; Cross-Sectional Studies; Malaysia/epidemiology; Risk Factors; Trypanosoma/genetics*; Trypanosomiasis/epidemiology; Trypanosomiasis/veterinary*; Prevalence; DNA, Protozoan/genetics; DNA Primers/genetics
4. Fulltext Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

   Fachal L, Aschard H, Beesley J, Barnes DR, Allen J, Kar S, et al.

   Nat Genet, 2020 01;52(1):56-73.

   PMID: 31911677 DOI: 10.1038/s41588-019-0537-1

   Abstract

   Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.

   MeSH terms: Bayes Theorem; Breast Neoplasms/genetics*; Chromosome Mapping/methods*; Female; Humans; Regulatory Sequences, Nucleic Acid; Risk Factors; Biomarkers, Tumor/genetics*; Linkage Disequilibrium; Genetic Predisposition to Disease*; Polymorphism, Single Nucleotide*; Quantitative Trait Loci*; Genome-Wide Association Study*
5. Fulltext Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

   Coleman JRI, Peyrot WJ, Purves KL, Davis KAS, Rayner C, Choi SW, et al.

   Mol Psychiatry, 2020 07;25(7):1430-1446.

   PMID: 31969693 DOI: 10.1038/s41380-019-0546-6

   Abstract

   Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8 × 10-7 versus rg = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10-4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

   MeSH terms: Psychological Trauma/epidemiology*; Adult; Aged; Depressive Disorder, Major/genetics*; Depressive Disorder, Major/epidemiology*; Female; Great Britain/epidemiology; Humans; Male; Middle Aged; Databases, Factual*; Genetic Predisposition to Disease/genetics*; Waist Circumference; Genome-Wide Association Study*; Self Report*; Gene-Environment Interaction*
6. Fulltext The use of the health belief model to assess predictors of intent to receive the COVID-19 vaccine and willingness to pay

   Wong LP, Alias H, Wong PF, Lee HY, AbuBakar S

   Hum Vaccin Immunother, 2020 09 01;16(9):2204-2214.

   PMID: 32730103 DOI: 10.1080/21645515.2020.1790279

   Abstract

   BACKGROUND: The development of a vaccine against SARS-CoV-2 infection is on the way. To prepare for public availability, the acceptability of a hypothetical COVID-19 vaccine and willingness to pay (WTP) were assessed to provide insights into future demand forecasts and pricing considerations.

   METHODS: A cross-sectional survey was conducted from 3 to 12 April 2020. The health belief model (HBM) was used to assess predictors of the intent to receive the vaccine and the WTP.

   RESULTS: A total of 1,159 complete responses was received. The majority reported a definite intent to receive the vaccine (48.2%), followed by a probable intent (29.8%) and a possible intent (16.3%). Both items under the perceived benefits construct in the HBM, namely believe the vaccination decreases the chance of infection (OR = 2.51, 95% CI 1.19-5.26) and the vaccination makes them feel less worry (OR = 2.19, 95% CI 1.03-4.65), were found to have the highest significant odds of a definite intention to take the vaccine. The mean ± standard deviation (SD) for the amount that participants were willing to pay for a dose of COVID-19 vaccine was MYR$134.0 (SD±79.2) [US$30.66 ± 18.12]. Most of the participants were willing to pay an amount of MYR$100 [US$23] (28.9%) and MYR$50 [US$11.5] (27.2%) for the vaccine. The higher marginal WTP for the vaccine was influenced by no affordability barriers as well as by socio-economic factors, such as higher education levels, professional and managerial occupations and higher incomes.

   CONCLUSIONS: The findings demonstrate the utility of HBM constructs in understanding COVID-19 vaccination intention and WTP.

   MeSH terms: Adolescent; Adult; Aged; Cross-Sectional Studies; Health Expenditures; Female; Humans; Malaysia/epidemiology; Male; Middle Aged; Models, Psychological; Patient Acceptance of Health Care/statistics & numerical data*; Pneumonia, Viral/prevention & control; Socioeconomic Factors; Vaccination/economics; Vaccination/psychology*; Viral Vaccines/economics; Coronavirus Infections/economics; Coronavirus Infections/prevention & control; Coronavirus Infections/psychology; Health Care Surveys; Young Adult; Pandemics/prevention & control
7. Fulltext European polygenic risk score for prediction of breast cancer shows similar performance in Asian women

   Ho WK, Tan MM, Mavaddat N, Tai MC, Mariapun S, Li J, et al.

   Nat Commun, 2020 07 31;11(1):3833.

   PMID: 32737321 DOI: 10.1038/s41467-020-17680-w

   Abstract

   Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.

   MeSH terms: Adult; Aged; Asia/epidemiology; Breast Neoplasms/diagnosis*; Breast Neoplasms/ethnology; Breast Neoplasms/genetics*; Breast Neoplasms/epidemiology; Europe/epidemiology; Female; Humans; Middle Aged; Prognosis; Risk; Odds Ratio; Case-Control Studies; Genetic Predisposition to Disease; Multifactorial Inheritance*; Polymorphism, Single Nucleotide*; Genome-Wide Association Study
8. Fulltext Comparison of eight complete chloroplast genomes of the endangered Aquilaria tree species (Thymelaeaceae) and their phylogenetic relationships

   Hishamuddin MS, Lee SY, Ng WL, Ramlee SI, Lamasudin DU, Mohamed R

   Sci Rep, 2020 08 03;10(1):13034.

   PMID: 32747724 DOI: 10.1038/s41598-020-70030-0

   Abstract

   Aquilaria tree species are naturally distributed in the Indomalesian region and are protected against over-exploitation. They produce a fragrant non-timber product of high economic value, agarwood. Ambiguous species delimitation and limited genetic information within Aquilaria are among the impediments to conservation efforts. In this study, we conducted comparative analysis on eight Aquilaria species complete chloroplast (cp) genomes, of which seven were newly sequenced using Illumina HiSeq X Ten platform followed by de novo assembly. Aquilaria cp genomes possess a typical quadripartite structure including gene order and genomic structure. The length of each of the cp genome is about 174 kbp and encoded between 89 and 92 proteins, 38 tRNAs, and 8 rRNAs, with 27 duplicated in the IR (inverted repeat) region. Besides, 832 repeats (forward, reverse, palindrome and complement repeats) and nine highly variable regions were also identified. The phylogenetic analysis suggests that the topology structure of Aquilaria cp genomes were well presented with strong support values based on the cp genomes data set and matches their geographic distribution pattern. In summary, the complete cp genomes will facilitate development of species-specific molecular tools to discriminate Aquilaria species and resolve the evolutionary relationships of members of the Thymelaeaceae family.

   MeSH terms: Base Composition/genetics; Base Sequence; Nucleotides/genetics; Phylogeny*; Species Specificity; Sequence Analysis, DNA; Thymelaeaceae/classification*; Thymelaeaceae/genetics*; Genome, Chloroplast*; Inverted Repeat Sequences/genetics; Molecular Sequence Annotation
9. Letter to the editor related to the article "stress in couples undergoing assisted reproductive technology" published by Tuncay et al

   Ahmad MF, Sidi H, Das S

   Arch Gynecol Obstet, 2021 03;303(3):853-854.

   PMID: 32876742 DOI: 10.1007/s00404-020-05756-3

   MeSH terms: Humans; Reproductive Techniques, Assisted*
10. Area-based conservation in the twenty-first century

    Maxwell SL, Cazalis V, Dudley N, Hoffmann M, Rodrigues ASL, Stolton S, et al.

    Nature, 2020 10;586(7828):217-227.

    PMID: 33028996 DOI: 10.1038/s41586-020-2773-z

    Abstract

    Humanity will soon define a new era for nature-one that seeks to transform decades of underwhelming responses to the global biodiversity crisis. Area-based conservation efforts, which include both protected areas and other effective area-based conservation measures, are likely to extend and diversify. However, persistent shortfalls in ecological representation and management effectiveness diminish the potential role of area-based conservation in stemming biodiversity loss. Here we show how the expansion of protected areas by national governments since 2010 has had limited success in increasing the coverage across different elements of biodiversity (ecoregions, 12,056 threatened species, 'Key Biodiversity Areas' and wilderness areas) and ecosystem services (productive fisheries, and carbon services on land and sea). To be more successful after 2020, area-based conservation must contribute more effectively to meeting global biodiversity goals-ranging from preventing extinctions to retaining the most-intact ecosystems-and must better collaborate with the many Indigenous peoples, community groups and private initiatives that are central to the successful conservation of biodiversity. The long-term success of area-based conservation requires parties to the Convention on Biological Diversity to secure adequate financing, plan for climate change and make biodiversity conservation a far stronger part of land, water and sea management policies.

    MeSH terms: Animals; Conservation of Natural Resources/economics; Conservation of Natural Resources/trends*; Conservation of Natural Resources/statistics & numerical data; Ecology/trends; Ecology/statistics & numerical data; Biodiversity; History, 21st Century; Wilderness; Aquatic Organisms; Geographic Mapping*