Displaying publications 1 - 20 of 48 in total

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  1. Zhang Y, Wu Q, Fang S, Li S, Zheng H, Zhang Y, et al.
    BMC Genomics, 2020 Aug 14;21(1):559.
    PMID: 32795331 DOI: 10.1186/s12864-020-06965-5
    BACKGROUND: Mud crab, Scylla paramamosain, a euryhaline crustacean species, mainly inhabits the Indo-Western Pacific region. Wild mud crab spawn in high-salt condition and the salinity reduced with the growth of the hatching larvae. When the larvae grow up to megalopa, they migrate back to estuaries and coasts in virtue of the flood tide, settle and recruit adult habitats and metamorphose into the crablet stage. Adult crab can even survive in a wide salinity of 0-35 ppt. To investigate the mRNA profile after salinity stress, S. paramamosain megalopa were exposed to different salinity seawater (low, 14 ppt; control, 25 ppt; high, 39 ppt).

    RESULTS: Firstly, from the expression profiles of Na+/K+/2Cl- cotransporter, chloride channel protein 2, and ABC transporter, it turned out that the 24 h might be the most influenced duration in the short-term stress. We collected megalopa under different salinity for 24 h and then submitted to mRNA profiling. Totally, 57.87 Gb Clean Data were obtained. The comparative genomic analysis detected 342 differentially expressed genes (DEGs). The most significantly DEGs include gamma-butyrobetaine dioxygenase-like, facilitated trehalose transporter Tret1, sodium/potassium-transporting ATPase subunit alpha, rhodanese 1-like protein, etc. And the significantly enriched pathways were lysine degradation, choline metabolism in cancer, phospholipase D signaling pathway, Fc gamma R-mediated phagocytosis, and sphingolipid signaling pathway. The results indicate that in the short-term salinity stress, the megalopa might regulate some mechanism such as metabolism, immunity responses, osmoregulation to adapt to the alteration of the environment.

    CONCLUSIONS: This study represents the first genome-wide transcriptome analysis of S. paramamosain megalopa for studying its stress adaption mechanisms under different salinity. The results reveal numbers of genes modified by salinity stress and some important pathways, which will provide valuable resources for discovering the molecular basis of salinity stress adaptation of S. paramamosain larvae and further boost the understanding of the potential molecular mechanisms of salinity stress adaptation for crustacean species.

  2. Jiang C, Zhu Y, Luo Y, Tan CS, Mastrotheodoros S, Costa P, et al.
    BMC Psychol, 2023 Oct 18;11(1):345.
    PMID: 37853499 DOI: 10.1186/s40359-023-01293-1
    BACKGROUND: The 10-item Rosenberg Self-Esteem Scale (RSES) is a widely used tool for individuals to self-report their self-esteem; however, the factorial structures of translated versions of the RSES vary across different languages. This study aimed to validate the Chinese version of the RSES in the Chinese mainland using a longitudinal design.

    METHODS: A group of healthcare university students completed the RSES across three waves: baseline, 1-week follow-up, and 15-week follow-up. A total of 481 valid responses were collected through the three-wave data collection process. Exploratory factor analysis (EFA) was performed on the baseline data to explore the potential factorial structure, while confirmatory factor analysis (CFA) was performed on the follow-up data to determine the best-fit model. Additionally, the cross-sectional and longitudinal measurement invariances were tested to assess the measurement properties of the RSES for different groups, such as gender and age, as well as across different time points. Convergent validity was assessed against the Self-Rated Health Questionnaire (SRHQ) using Spearman's correlation. Internal consistency was examined using Cronbach's alpha and McDonald's omega coefficients, while test-retest reliability was assessed using intraclass correlation coefficient.

    RESULTS: The results of EFA revealed that Items 5, 8, and 9 had inadequate or cross-factor loadings, leading to their removal from further analysis. Analysis of the remaining seven items using EFA suggested a two-factor solution. A comparison of several potential models for the 10-item and 7-item RSES using CFA showed a preference for the 7-item form (RSES-7) with two factors. Furthermore, the RSES-7 exhibited strict invariance across different groups and time points, indicating its stability and consistency. The RSES-7 also demonstrated adequate convergent validity, internal consistency, and test-retest reliability, which further supported its robustness as a measure of self-esteem.

    CONCLUSIONS: The findings suggest that the RSES-7 is a psychometrically sound and brief self-report scale for measuring self-esteem in the Chinese context. More studies are warranted to further verify its usability.

  3. Zhang Y, Miao G, Fazhan H, Waiho K, Zheng H, Li S, et al.
    Physiol Genomics, 2018 05 01;50(5):393-405.
    PMID: 29570432 DOI: 10.1152/physiolgenomics.00016.2018
    The crucifix crab, Charybdis feriatus, which mainly inhabits Indo-Pacific region, is regarded as one of the most high-potential species for domestication and incorporation into the aquaculture sector. However, the regulatory mechanisms of sex determination and differentiation of this species remain unclear. To identify candidate genes involved in sex determination and differentiation, high throughput sequencing of transcriptome from the testis and ovary of C. feriatus was performed by the Illumina platform. After removing adaptor primers, low-quality sequences and very short (<50 nt) reads, we obtained 80.9 million and 66.2 million clean reads from testis and ovary, respectively. A total of 86,433 unigenes were assembled, and ~43% (37,500 unigenes) were successfully annotated to the NR, NT, Swiss-Prot, KEGG, COG, GO databases. By comparing the testis and ovary libraries, we obtained 27,636 differentially expressed genes. Some candidate genes involved in the sex determination and differentiation of C. feriatus were identified, such as vasa, pgds, vgr, hsp90, dsx-f, fem-1, and gpr. In addition, 88,608 simple sequence repeats were obtained, and 61,929 and 77,473 single nucleotide polymorphisms from testis and ovary were detected, respectively. The transcriptome profiling was validated by quantitative real-time PCR in 30 selected genes, which showed a good consistency. The present study is the first high-throughput transcriptome sequencing of C. feriatus. These findings will be useful for future functional analysis of sex-associated genes and molecular marker-assisted selections in C. feriatus.
  4. Syafaat MN, Azra MN, Mohamad F, Che-Ismail CZ, Amin-Safwan A, Asmat-Ullah M, et al.
    Animals (Basel), 2021 Apr 16;11(4).
    PMID: 33923853 DOI: 10.3390/ani11041146
    This study was carried out to determine the physiological changes (survival, growth, molting cycle, sex differentiation, and gill condition) of mud crab, Scylla paramamosain crablet at different water temperatures of 24, 28 and 32 °C, and ambient temperature of 27 to 30 °C. Thermoregulatory behavior, represented by preferred temperature (29.83 ± SD 2.47 °C), critical thermal minimum (17.33 ± SD 0.58 °C), critical thermal maximum (40 ± SD 0.00 °C), and thermal tolerance interval (22.67 ± SD 0.58 °C), were checked for Crablet 1 stage only (with ambient temperature as acclimation temperature).Both low (24 °C) and high (32 °C) temperatures were associated with lower growth performance, and survival rate (p < 0.05), in comparison with both 28 °C and ambient temperature treatments.Male ratio at low temperaturetreatment (24 °C) was higher (80.09 ± SD 18.86%) than for other treatments (p < 0.05), observed as 44.81 ± D 10.50%, 41.94 ± SD 19.44%, and 76.30 ± SD 5.13% for 28 °C, 32 °C and ambient temperature treatments, respectively. However, there was no significant difference observed between 24 °C, 28 °C, and ambient temperature treatments. Anatomical alterations of gill lamellae of S. paramamosain crablet for both 32 °C, and 24 °C treatments, appeared thinner and paler than at both 28 °C, and ambient temperature treatments. Based on this study, temperature of 28 to 30 °C was recommended as the optimal temperature for the long-term nursery phase of S. paramamosain.
  5. Guan M, Liu X, Lin F, Xie Z, Fazhan H, Ikhwanuddin M, et al.
    Mitochondrial DNA B Resour, 2018 Mar 14;3(1):368-369.
    PMID: 33490509 DOI: 10.1080/23802359.2018.1450685
    In this study, we sequenced and analyzed the whole mitochondrial genome of Metopograpsus frontalis Miers, 1880 (Decapoda, Grapsidae). The circular genome is 15,587 bp in length, consisting of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, as well as a control region. Both atp8/atp6 and nad4L/nad4 share 7 nucleotides in their adjacent overlapping region, which is identical to those observed in other Grapsidae crabs. The genome composition and gene order follow a classic crab-type arrangement regulation. The phylogenetic analysis suggested that Grapsidae crabs formed a solid monophyletic group. The newly described mitochondrial genome may provide genetic marker for studies on phylogeny of the grapsid crabs.
  6. Guan M, Tan H, Fazhan H, Xie Z, Shi X, Zhang Y, et al.
    Mitochondrial DNA B Resour, 2018 Oct 26;3(2):1244-1245.
    PMID: 33474478 DOI: 10.1080/23802359.2018.1532345
    The mitochondrial genome plays an important role in studies on phylogeography and population genetic diversity. Here we report the complete mitochondrial genome of Lupocycloporus gracilimanus (Stimpson, 1858) which is the first mitochondrial genome reported in genus Lupocycloporus by now. The mitogenome is 15,990 bp in length, consisting of 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and a putative control region. The phylogenetic analysis showed that L. gracilimanus was closest to genus Scylla. The present research should provide valuable information for phylogenetic analysis and classification of Portunidae.
  7. Farhadi A, Fang S, Zhang Y, Cui W, Fang H, Ikhwanuddin M, et al.
    Int J Biol Macromol, 2021 Jul 31;183:490-501.
    PMID: 33957197 DOI: 10.1016/j.ijbiomac.2021.04.186
    The wingless-type MMTV integration site family member-4 (Wnt4), a member of the wingless-related integration site (Wnt) family, is widely accepted as a key regulator of ovarian development in mammals. In this study, a full-length cDNA of Wnt4 (designated as Sp-Wnt4) was cloned, characterized, and functionally studied in mud crab (Scylla paramamosain). The full-length cDNA of Sp-Wnt4 consists of 2659 bp with an open reading frame (ORF) encoding 359 amino acids, a 907 bp 5'-UTR and a 672 bp 3'-UTR. Sp-Wnt4 contains 25 cysteine (Cys) residues and three potential N-glycosylation sites. Sp-Wnt4 protein shared the highest identity (98.9%) to the Wnt4 protein of Portunus trituberculatus. The phylogenetic tree showed that Sp-Wnt4 and Wnt4 protein of Malacostracan crustaceans clustered together, indicating that they had a close genetic distance. Sp-Wnt4 was expressed at a higher level in the ovary compared to other tissues, with the highest expression level at the third stage (O-III) of the ovarian development (P < 0.05). A downward trend was observed in the expression level of Sp-Wnt4 from the embryo stage to crablet stages (P < 0.05). After unilateral eyestalk ablation, the expression level of Sp-Wnt4 significantly increased in testis (14-fold) and downregulated (3.1-fold) in the gill (P < 0.05) of females. In situ hybridization (ISH) assay revealed that Sp-Wnt4 transcripts were mainly localized in the cytoplasm of oocyte cells. These findings showed that Sp-Wnt4 play crucial roles in the ovarian development of S. paramamosain. In conclusion, our study provides novel insights into the evolution and roles of the Wnt4 gene.
  8. Ma H, Crowther TW, Mo L, Maynard DS, Renner SS, van den Hoogen J, et al.
    Nat Plants, 2023 Nov;9(11):1795-1809.
    PMID: 37872262 DOI: 10.1038/s41477-023-01543-5
    Understanding what controls global leaf type variation in trees is crucial for comprehending their role in terrestrial ecosystems, including carbon, water and nutrient dynamics. Yet our understanding of the factors influencing forest leaf types remains incomplete, leaving us uncertain about the global proportions of needle-leaved, broadleaved, evergreen and deciduous trees. To address these gaps, we conducted a global, ground-sourced assessment of forest leaf-type variation by integrating forest inventory data with comprehensive leaf form (broadleaf vs needle-leaf) and habit (evergreen vs deciduous) records. We found that global variation in leaf habit is primarily driven by isothermality and soil characteristics, while leaf form is predominantly driven by temperature. Given these relationships, we estimate that 38% of global tree individuals are needle-leaved evergreen, 29% are broadleaved evergreen, 27% are broadleaved deciduous and 5% are needle-leaved deciduous. The aboveground biomass distribution among these tree types is approximately 21% (126.4 Gt), 54% (335.7 Gt), 22% (136.2 Gt) and 3% (18.7 Gt), respectively. We further project that, depending on future emissions pathways, 17-34% of forested areas will experience climate conditions by the end of the century that currently support a different forest type, highlighting the intensification of climatic stress on existing forests. By quantifying the distribution of tree leaf types and their corresponding biomass, and identifying regions where climate change will exert greatest pressure on current leaf types, our results can help improve predictions of future terrestrial ecosystem functioning and carbon cycling.
  9. Lin F, Xie Z, Fazhan H, Baylon JC, Yang X, Tan H, et al.
    Mitochondrial DNA B Resour, 2018 Feb 23;3(1):263-264.
    PMID: 33474136 DOI: 10.1080/23802359.2018.1443043
    The complete mitochondrial genome plays an important role in the research on phylogenetic relationship. Here, we reported the first complete mitochondrial genome sequence of Varuna yui Hwang & Takeda, 1986 (Varunidae). The complete mtDNA (15,915 bp in length) consisted of 13 protein-coding genes, 22 tRNAs, two rRNA genes, and a control region. The gene arrangement was identical to those observed in the Varunidae species. The phylogenetic analysis suggested that V. yui had close relationship with other Varunidae species (Helicetient sinensis, Eriocher sinesis, etc.). The newly described genome may facilitate further comparative mitogenomic analysis within Varunidae species.
  10. Zheng Z, Aweya JJ, Bao S, Yao D, Li S, Tran NT, et al.
    J Immunol, 2021 12 01;207(11):2733-2743.
    PMID: 34670821 DOI: 10.4049/jimmunol.2100746
    Aquatic organisms have to produce proteins or factors that help maintain a stable relationship with microbiota and prevent colonization by pathogenic microorganisms. In crustaceans and other aquatic invertebrates, relatively few of these host factors have been characterized. In this study, we show that the respiratory glycoprotein hemocyanin is a crucial host factor that modulates microbial composition and diversity in the hepatopancreas of penaeid shrimp. Diseased penaeid shrimp (Penaeus vannamei), had an empty gastrointestinal tract with atrophied hepatopancreas, expressed low hemocyanin, and high total bacterial abundance, with Vibrio as the dominant bacteria. Similarly, shrimp depleted of hemocyanin had mitochondrial depolarization, increased reactive oxygen species (ROS) levels, and dysregulation of several energy metabolism-related genes. Hemocyanin silencing together with ROS scavenger (N-acetylcysteine) treatment improved microbial diversity and decreased Vibrio dominance in the hepatopancreas. However, fecal microbiota transplantation after hemocyanin knockdown could not restore the microbial composition in the hepatopancreas. Collectively, our data provide, to our knowledge, new insight into the pivotal role of hemocyanin in modulating microbial composition in penaeid shrimp hepatopancreas via its effect on mitochondrial integrity, energy metabolism, and ROS production.
  11. Ghoreishi A, Arsang-Jang S, Sabaa-Ayoun Z, Yassi N, Sylaja PN, Akbari Y, et al.
    J Stroke Cerebrovasc Dis, 2020 Dec;29(12):105321.
    PMID: 33069086 DOI: 10.1016/j.jstrokecerebrovasdis.2020.105321
    BACKGROUND: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran.

    METHODS: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model.

    RESULTS: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p 

  12. Fazhan H, Waiho K, Fujaya Y, Rukminasari N, Ma H, Ikhwanuddin M
    PeerJ, 2021;9:e10936.
    PMID: 33954025 DOI: 10.7717/peerj.10936
    Sexual dimorphism is a common phenomenon in the animal kingdom. To test the consistency of sexual dimorphism patterns among sympatric species of the same genus, ten morphometric characteristics of mud crabs Scylla olivacea, S. tranquebarica and S. paramamosain were measured and compared using Discriminant Function Analysis (DFA). The descriptive analysis revealed that in all three species, body size dimensions and cheliped dimensions were significantly larger in males whereas the abdomen width was female-biased. Also, we described a morphological variation (carapace width, CW ≤ CW at spine 8, 8CW) that is unique to S. olivacea. Discriminant function analysis revealed that all nine morphometric characteristics were sexually dimorphic in S. olivacea, S. tranquebarica (except right cheliped's merus length, ML) and S. paramamosain (except 8CW). The obtained discriminant functions based on the morphometric ratios (with CW as divisor) correctly classified 100% of adults of known sex of all three species. Further, based on the selected body traits, DFA was able to almost completely distinguish males (94%), but not females (74%), among the three Scylla species. This study highlights that congeneric species of portunids (e.g., Scylla spp.) show similar sexually dimorphic characteristics (body size and secondary sexual characteristics).
  13. Tan K, Zhang H, Lim LS, Ma H, Li S, Zheng H
    Front Immunol, 2019;10:3041.
    PMID: 32010132 DOI: 10.3389/fimmu.2019.03041
    Carotenoids are biologically active pigments that are well-known to enhance the defense and immunity of the vertebrate system. However, in invertebrates, the role of carotenoids in immunity is not clear. Therefore, this study aims to review the scientific evidence for the role of carotenoids in invertebrate immunization. From the analysis of published literatures and recent studies from our laboratory, it is obvious that carotenoids are involved in invertebrate immunity in two ways. On the one hand, carotenoids can act as antioxidant enzymes to remove singlet oxygen, superoxide anion radicals, and hydroxyl radicals, thereby reducing SOD activity and reducing the cost of immunity. In some organisms, carotenoids have been shown to promote SOD activity by up-regulating the expression of the ZnCuSOD gene. Carotenoids, on the other hand, play a role in the expression and regulation of many genes involved in invertebrate immunity, including thioredoxins (TRX), peptidoglycan recognition receptor proteins (PGRPs), ferritins, prophenoloxidase (ProPO), vitellogenin (Vg), toll-like receptor (TLRs), heat shock proteins (HSPs), and CuZnSOD gene. The information in this review is very useful for updating our understanding of the progress of carotenoid research in invertebrate immunology and to help identify topics for future topics.
  14. Gao M, Lin Y, Wang P, Jin Y, Wang Q, Ma H, et al.
    J Hazard Mater, 2021 Sep 05;417:126037.
    PMID: 33992013 DOI: 10.1016/j.jhazmat.2021.126037
    Chinese liquor distillers' grain (CLDG) is an abundant industrial organic waste showing high potential as feedstock for biofuel conversion. In this study, CLDG was used as substrate by microbial community in pit mud to produce medium-chain fatty acids (especially caproate). Simulated and real fermentation were used to evaluate the effect of ethanol and lactic acid being the electronic donors (EDs) during the anaerobic chain elongation (CE). The caproate concentration was achieved at 449 mg COD/g VS, with the corresponding high carbon selectivity at 37.1%. Microbial analysis revealed that the domestication of pit mud increased the abundance of Caproiciproducens (converting lactic acid into caproate) and Lactobacillus (producing lactic acid), leading to enhanced caproate production. The lactic acid conversion facilitated in full utilization of ethanol through CE consumption. The coexistence of EDs benefited the CE system and that this green energy production can be a promising high-performance biofuel donor for sustainable industrial production development.
  15. Zhao J, Ma H, Wu W, Ali Bacar M, Wang Q, Gao M, et al.
    Bioresour Technol, 2023 Jan;368:128375.
    PMID: 36414142 DOI: 10.1016/j.biortech.2022.128375
    Substrate toxicity would limit the upgrading of waste biomass to medium-chain fatty acids (MCFAs). In this work, two fermentation modes of electro-fermentation (EF) and traditional fermentation (TF) with different concentration of liquor fermentation waste (20%, 40%, 60%) were used for MCFAs production as well as mechanism investigation. The highest caproate (4.04 g/L) and butyrate (13.96 g/L) concentrations were obtained by EF at 40% substrate concentration. TF experiments showed that the substrate concentration above 40% severely inhibited ethanol oxidation and products formation. Compared with TF mode, the total substrates consumption and product yields under EF mode were significantly increased by 2.6%-43.5% and 54.0%-83.0%, respectively. Microbial analysis indicated that EF effectively alleviated substrate toxicity and enriched chain elongation bacteria, particularly Clostridium_sensu_stricto 12, thereby promoting ethanol oxidation and products formation. Caproiciproducens tolerated high-concentration substrates to ensure normal lactate metabolism. This study provides a new way to produce MCFAs from high concentration wastewater.
  16. Fazhan H, Waiho K, Quinitio E, Baylon JC, Fujaya Y, Rukminasari N, et al.
    PeerJ, 2020;8:e8066.
    PMID: 31915566 DOI: 10.7717/peerj.8066
    There are four species of mud crabs within the genus Scylla, and most of them live sympatrically in the equatorial region. Apart from a report in Japan about the finding of a natural Scylla hybrid more than a decade ago after the division of genus Scylla into four species by Keenan, Davie & Mann (1998), no subsequent sighting was found. Thus, this study investigates the possible natural occurrence of potential hybridization among Scylla species in the wild. A total of 76,211 individuals from mud crab landing sites around the Malacca Straits, South China Sea and Sulu Sea were screened. In addition to the four-purebred species, four groups (SH 1, n = 2, 627; SH 2, n = 136; SH 3, n = 1; SH 4, n = 2) with intermediate characteristics were found, mostly at Sulu Sea. Discriminant Function Analysis revealed that all Scylla species, including SH 1 - 4, are distinguishable via their morphometric ratios. The most powerful discriminant ratios for each character and the top five discriminant ratios of males and females were suggested. The carapace width of SH 1 males and females were significantly smaller than pure species. Based on the discriminant ratios and the description of morphological characters, we hypothesize that the additional four groups of Scylla with intermediate characteristics could be presumed hybrids. Future work at the molecular level is urgently needed to validate this postulate.
  17. Yang F, Guo GZ, Chen JQ, Ma HW, Liu T, Huang DN, et al.
    Epidemiol Infect, 2014 Feb;142(2):225-33.
    PMID: 23587429 DOI: 10.1017/S0950268813000897
    A suspected dengue fever outbreak occurred in 2010 at a solitary construction site in Shenzhen city, China. To investigate this epidemic, we used serological, molecular biological, and bioinformatics techniques. Of nine serum samples from suspected patients, we detected seven positive for dengue virus (DENV) antibodies, eight for DENV-1 RNA, and three containing live viruses. The isolated virus, SZ1029 strain, was sequenced and confirmed as DENV-1, showing the highest E-gene homology to D1/Malaysia/36000/05 and SG(EHI)DED142808 strains recently reported in Southeast Asia. Further phylogenetic tree analysis confirmed their close relationship. At the epidemic site, we also detected 14 asymptomatic co-workers (out of 291) positive for DENV antibody, and DENV-1-positive mosquitoes. Thus, we concluded that DENV-1 caused the first local dengue fever outbreak in Shenzhen. Because no imported case was identified, the molecular fingerprints of the SZ1029 strain suggest this outbreak may be due to vertical transmission imported from Southeast Asia.
  18. Burton A, Byrnes G, Stone J, Tamimi RM, Heine J, Vachon C, et al.
    Breast Cancer Res, 2016 12 19;18(1):130.
    PMID: 27993168
    BACKGROUND: Inter-women and intra-women comparisons of mammographic density (MD) are needed in research, clinical and screening applications; however, MD measurements are influenced by mammography modality (screen film/digital) and digital image format (raw/processed). We aimed to examine differences in MD assessed on these image types.

    METHODS: We obtained 1294 pairs of images saved in both raw and processed formats from Hologic and General Electric (GE) direct digital systems and a Fuji computed radiography (CR) system, and 128 screen-film and processed CR-digital pairs from consecutive screening rounds. Four readers performed Cumulus-based MD measurements (n = 3441), with each image pair read by the same reader. Multi-level models of square-root percent MD were fitted, with a random intercept for woman, to estimate processed-raw MD differences.

    RESULTS: Breast area did not differ in processed images compared with that in raw images, but the percent MD was higher, due to a larger dense area (median 28.5 and 25.4 cm2 respectively, mean √dense area difference 0.44 cm (95% CI: 0.36, 0.52)). This difference in √dense area was significant for direct digital systems (Hologic 0.50 cm (95% CI: 0.39, 0.61), GE 0.56 cm (95% CI: 0.42, 0.69)) but not for Fuji CR (0.06 cm (95% CI: -0.10, 0.23)). Additionally, within each system, reader-specific differences varied in magnitude and direction (p 

  19. Burton A, Maskarinec G, Perez-Gomez B, Vachon C, Miao H, Lajous M, et al.
    PLoS Med, 2017 Jun;14(6):e1002335.
    PMID: 28666001 DOI: 10.1371/journal.pmed.1002335
    BACKGROUND: Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known.

    METHODS AND FINDINGS: We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35-85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (-0.46 cm [95% CI: -0.53, -0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was -0.24 cm (95% CI: -0.34, -0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (-0.38 cm [95% CI: -0.44, -0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature.

    CONCLUSIONS: Declines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction.

  20. McCormack VA, Burton A, dos-Santos-Silva I, Hipwell JH, Dickens C, Salem D, et al.
    Cancer Epidemiol, 2016 Feb;40:141-51.
    PMID: 26724463 DOI: 10.1016/j.canep.2015.11.015
    Mammographic density (MD) is a quantitative trait, measurable in all women, and is among the strongest markers of breast cancer risk. The population-based epidemiology of MD has revealed genetic, lifestyle and societal/environmental determinants, but studies have largely been conducted in women with similar westernized lifestyles living in countries with high breast cancer incidence rates. To benefit from the heterogeneity in risk factors and their combinations worldwide, we created an International Consortium on Mammographic Density (ICMD) to pool individual-level epidemiological and MD data from general population studies worldwide. ICMD aims to characterize determinants of MD more precisely, and to evaluate whether they are consistent across populations worldwide. We included 11755 women, from 27 studies in 22 countries, on whom individual-level risk factor data were pooled and original mammographic images were re-read for ICMD to obtain standardized comparable MD data. In the present article, we present (i) the rationale for this consortium; (ii) characteristics of the studies and women included; and (iii) study methodology to obtain comparable MD data from original re-read films. We also highlight the risk factor heterogeneity captured by such an effort and, thus, the unique insight the pooled study promises to offer through wider exposure ranges, different confounding structures and enhanced power for sub-group analyses.
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