Browsing by Author "Kim J"

Now showing 1 - 7 of 7
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    Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations.
    (Springer Nature, 2023-10-02) Thomas M; Su Y-R; Rosenthal EA; Sakoda LC; Schmit SL; Timofeeva MN; Chen Z; Fernandez-Rozadilla C; Law PJ; Murphy N; Carreras-Torres R; Diez-Obrero V; van Duijnhoven FJB; Jiang S; Shin A; Wolk A; Phipps AI; Burnett-Hartman A; Gsur A; Chan AT; Zauber AG; Wu AH; Lindblom A; Um CY; Tangen CM; Gignoux C; Newton C; Haiman CA; Qu C; Bishop DT; Buchanan DD; Crosslin DR; Conti DV; Kim D-H; Hauser E; White E; Siegel E; Schumacher FR; Rennert G; Giles GG; Hampel H; Brenner H; Oze I; Oh JH; Lee JK; Schneider JL; Chang-Claude J; Kim J; Huyghe JR; Zheng J; Hampe J; Greenson J; Hopper JL; Palmer JR; Visvanathan K; Matsuo K; Matsuda K; Jung KJ; Li L; Le Marchand L; Vodickova L; Bujanda L; Gunter MJ; Matejcic M; Jenkins MA; Slattery ML; D'Amato M; Wang M; Hoffmeister M; Woods MO; Kim M; Song M; Iwasaki M; Du M; Udaltsova N; Sawada N; Vodicka P; Campbell PT; Newcomb PA; Cai Q; Pearlman R; Pai RK; Schoen RE; Steinfelder RS; Haile RW; Vandenputtelaar R; Prentice RL; Küry S; Castellví-Bel S; Tsugane S; Berndt SI; Lee SC; Brezina S; Weinstein SJ; Chanock SJ; Jee SH; Kweon S-S; Vadaparampil S; Harrison TA; Yamaji T; Keku TO; Vymetalkova V; Arndt V; Jia W-H; Shu X-O; Lin Y; Ahn Y-O; Stadler ZK; Van Guelpen B; Ulrich CM; Platz EA; Potter JD; Li CI; Meester R; Moreno V; Figueiredo JC; Casey G; Lansdorp Vogelaar I; Dunlop MG; Gruber SB; Hayes RB; Pharoah PDP; Houlston RS; Jarvik GP; Tomlinson IP; Zheng W; Corley DA; Peters U; Hsu L
    Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
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    Effect of Process and Formulation Variables on the Structural and Physical Properties in Cream Cheese using GDL Acidulant
    (Springer Science+Business Media, LLC, 2022-06) Kim J; Watkinson P; Lad M; Matia-Merino L; Smith JR; Golding M
    We report on the properties of analogue cream cheeses prepared using glucono delta-lactone (GDL) acidulant, notably the impact of particular processing and formulation variables, (homogenisation pressure, coagulation pH and temperature, and stabiliser level) on cream cheese physical, material and microstructural properties. Protein–protein and protein-fat interactions were seen to be the primary structural contributors to the physical properties of cream cheese. Cream cheese microstructure and its properties demonstrated well-defined correlations to specific and controllable processing elements within the manufacturing process, showing significance in interactions between parameters in multivariable linear regression analysis (P < 0.05). Summarising the effect of processing variables on key cheese properties, we observed that a progressive reduction in fat particle size of cheese milk arising from increasing homogenisation pressures was seen to increase the total surface area of fat that could be incorporated into the curd during coagulation. The greater extent of fat-fat and fat-proteins interactions during coagulation provided a reinforcing effect on the microstructure of the final cream cheese, with a corresponding increase in compressive fracture stress, shear storage modulus (G′) and shear loss modulus (G″). In terms of other processing variables, cream cheese firmness was also observed to progressively increase through lowering of coagulation pH from 5.13 to 4.33. Increasing coagulation temperature from 58 °C to 78 °C similarly caused an increase in cheese firmness. Finally, increasing the levels of added stabiliser were shown to correlate with increasing cheese firmness. Similar correlations could be observed in relation to physical properties, notably forced expressible serum separation. This model cream cheese preparation method has provided a useful model system for relating food structure to material and functional properties. In addition, it has the advantage of being able to rapidly screen many formulation and process variables because it is faster than the traditional cheesemaking. This study showed that the adjustment of process and formulation variables, either in isolation or in combination, in the manufacture of cream cheese can significantly influence the final material and textural properties of the product, thereby enabling controllable functional attributes capable of meeting different customer needs.
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    EP400NL is involved in PD-L1 gene activation by forming a transcriptional coactivator complex
    (Elsevier B V, 2023-03) Li Z; Kim H; Kim J; Park JH
    EP400 is an ATP-dependent chromatin remodelling enzyme that regulates DNA double-strand break repair and transcription, including cMyc-dependent gene expression. We previously showed that the N-terminal domain of EP400 increases the efficacy of chemotherapeutic drugs against cancer cells. As the EP400 N-terminal-Like (EP400NL) gene resides next to the EP400 gene locus, this prompted us to investigate whether EP400NL plays a similar role in transcriptional regulation to the full-length EP400 protein. We found that EP400NL forms a human NuA4-like chromatin remodelling complex that lacks both the TIP60 histone acetyltransferase and EP400 ATPase. However, this EP400NL complex displays H2A.Z deposition activity on a chromatin template comparable to the human NuA4 complex, suggesting another associated ATPase such as BRG1 or RuvBL1/RuvBL2 catalyses the reaction. We demonstrated that the transcriptional coactivator function of EP400NL is required for serum and IFNγ-induced PD-L1 gene activation. Furthermore, transcriptome analysis indicates that EP400NL contributes to cMyc-responsive mitochondrial biogenesis. Taken together, our studies show that EP400NL plays a role as a transcription coactivator of PD-L1 gene regulation and provides a potential target to modulate cMyc functions in cancer therapy.
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    Evaluation of formulation design on the physical and structural properties of commercial cream cheeses
    (John Wiley and Sons Ltd on behalf of Institute of Food, Science and Technology (IFSTTF)., 2022-10) Kim J; Watkinson P; Matia-Merino L; Smith JR; Golding M
    This study investigated how the compositional properties and formulation design of commercial cream cheese products model cheese influenced physical and structural properties as compared to a model cheese composition. Of the seven products evaluated, three were block format (B), two were spreadable (S) and two were spreadable light (SL), with fat contents ranging from 13.7 to 35.7%. The majority of cream cheese products indicated the inclusion of starter culture, and all formulations contained one or more stabilisers. Protein/moisture (p/m) ratio, i.e. the effective protein concentration in the non-fat substance, was seen to most strongly correlate with material properties, with a positive slope for fracture stress (R2 = 0.808) and modulus of deformability (R2 = 0.721). In terms of outliers, the datapoint for SL2 on this modulus versus p/m graph was lower than its regression line, and one rationale is that lower fat content (13.7%) gave a lower modulus from the milkfat component at 10°C test temperature. B1, with the highest p/m of 0.17, had a more dense distribution of larger fat globules coated with proteins than B2 and B3. Fracture stress and modulus of deformability were noted to be higher for full-fat than for lower fat cheese. In all products, elastic characteristics dominated viscous flow as expected. Findings have demonstrated that significant variance exists across the material properties of commerical cream cheeses, and which shows specific dependencies on their formulation.
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    Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.
    (Springer Nature, 2024-04-26) Chen Z; Guo X; Tao R; Huyghe JR; Law PJ; Fernandez-Rozadilla C; Ping J; Jia G; Long J; Li C; Shen Q; Xie Y; Timofeeva MN; Thomas M; Schmit SL; Díez-Obrero V; Devall M; Moratalla-Navarro F; Fernandez-Tajes J; Palles C; Sherwood K; Briggs SEW; Svinti V; Donnelly K; Farrington SM; Blackmur J; Vaughan-Shaw PG; Shu X-O; Lu Y; Broderick P; Studd J; Harrison TA; Conti DV; Schumacher FR; Melas M; Rennert G; Obón-Santacana M; Martín-Sánchez V; Oh JH; Kim J; Jee SH; Jung KJ; Kweon S-S; Shin M-H; Shin A; Ahn Y-O; Kim D-H; Oze I; Wen W; Matsuo K; Matsuda K; Tanikawa C; Ren Z; Gao Y-T; Jia W-H; Hopper JL; Jenkins MA; Win AK; Pai RK; Figueiredo JC; Haile RW; Gallinger S; Woods MO; Newcomb PA; Duggan D; Cheadle JP; Kaplan R; Kerr R; Kerr D; Kirac I; Böhm J; Mecklin J-P; Jousilahti P; Knekt P; Aaltonen LA; Rissanen H; Pukkala E; Eriksson JG; Cajuso T; Hänninen U; Kondelin J; Palin K; Tanskanen T; Renkonen-Sinisalo L; Männistö S; Albanes D; Weinstein SJ; Ruiz-Narvaez E; Palmer JR; Buchanan DD; Platz EA; Visvanathan K; Ulrich CM; Siegel E; Brezina S; Gsur A; Campbell PT; Chang-Claude J; Hoffmeister M; Brenner H; Slattery ML; Potter JD; Tsilidis KK; Schulze MB; Gunter MJ; Murphy N; Castells A; Castellví-Bel S; Moreira L; Arndt V; Shcherbina A; Bishop DT; Giles GG; Southey MC; Idos GE; McDonnell KJ; Abu-Ful Z; Greenson JK; Shulman K; Lejbkowicz F; Offit K; Su Y-R; Steinfelder R; Keku TO; van Guelpen B; Hudson TJ; Hampel H; Pearlman R; Berndt SI; Hayes RB; Martinez ME; Thomas SS; Pharoah PDP; Larsson SC; Yen Y; Lenz H-J; White E; Li L; Doheny KF; Pugh E; Shelford T; Chan AT; Cruz-Correa M; Lindblom A; Hunter DJ; Joshi AD; Schafmayer C; Scacheri PC; Kundaje A; Schoen RE; Hampe J; Stadler ZK; Vodicka P; Vodickova L; Vymetalkova V; Edlund CK; Gauderman WJ; Shibata D; Toland A; Markowitz S; Kim A; Chanock SJ; van Duijnhoven F; Feskens EJM; Sakoda LC; Gago-Dominguez M; Wolk A; Pardini B; FitzGerald LM; Lee SC; Ogino S; Bien SA; Kooperberg C; Li CI; Lin Y; Prentice R; Qu C; Bézieau S; Yamaji T; Sawada N; Iwasaki M; Le Marchand L; Wu AH; Qu C; McNeil CE; Coetzee G; Hayward C; Deary IJ; Harris SE; Theodoratou E; Reid S; Walker M; Ooi LY; Lau KS; Zhao H; Hsu L; Cai Q; Dunlop MG; Gruber SB; Houlston RS; Moreno V; Casey G; Peters U; Tomlinson I; Zheng W
    Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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    Geographic Disparities in Stroke Outcomes and Service Access: A Prospective Observational Study
    (Wolters Kluwer Health, Inc on behalf of the American Academy of Neurology, 26/07/2022) Thompson SG; Barber PA; Gommans JH; Cadilhac DA; Davis A; Fink JN; Harwood M; Levack W; McNaughton HK; Feigin VL; Abernethy V; Girvan J; Kim J; Denison H; Corbin M; Wilson A; Douwes J; Ranta A
    BACKGROUND AND OBJECTIVE: International evidence shows that patients treated at non-urban hospitals experience poorer access to key stroke interventions. Evidence whether this results in poorer outcomes is conflicting and generally based on administrative or voluntary registry data. The aim of this study was to use prospective high-quality comprehensive nationwide patient level data to investigate the association between hospital geography and stroke patient outcomes and access to best practice stroke care in New Zealand. METHODS: This is a prospective, multi-centre, nationally representative observational study involving all 28 New Zealand acute stroke hospitals (18 non-urban), and affiliated rehabilitation and community services. Consecutive adults admitted to the hospital with acute stroke between 1 May and 31 October 2018 were captured. Outcomes included functional outcome (modified Rankin Scale (mRS) shift analysis), functional independence (mRS scores 0-2), quality of life (EQ5D-3L), stroke/vascular events, and death at 3, 6, and 12 months and proportion accessing thrombolysis, thrombectomy, stroke units, key investigations, secondary prevention, and inpatient/community rehabilitation. Results were adjusted for age, sex, ethnicity, stroke severity/type, co-morbidities, baseline function, and differences in baseline characteristics. RESULTS: Overall, 2,379 patients were eligible (mean (standard deviation) age 75 (13.7); 51.2% male; 1,430 urban; 949 non-urban). Patients treated at non-urban hospitals were more likely to score in a higher mRS category (greater disability) at three (aOR=1.28, 1.07-1.53), six (aOR=1.33, 1.07-1.65) and twelve months (aOR=1.31, 1.06-1.62) and were more likely to have died (aOR=1.57, 1.17-2.12) or experienced recurrent stroke and vascular events at 12 months (aOR=1.94, 1.14-3.29 and aOR=1.65, 1.09-2.52). Fewer non-urban patients received recommended stroke interventions including endovascular thrombectomy (aOR=0.25, 95% confidence interval 0.13-0.49), acute stroke unit care (aOR=0.60, 0.49-0.73), antiplatelet prescriptions (aOR=0.72, 0.58-0.88), ≥60 minutes daily physical therapy (aOR=0.55, 0.40-0.77) and community rehabilitation (aOR=0.69, 0.56-0.84). DISCUSSION: Patients managed at non-urban hospitals experience poorer stroke outcomes and reduced access to key stroke interventions across the entire care continuum. Efforts to improve access to high quality stroke care in non-urban hospitals should be a priority.
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    Human model effect? Online visual presentation of fashion merchandise
    (Association for Consumer Research, 1/05/2016) Kim JE; Kim K; Kim J