Displaying publications 81 - 100 of 166 in total

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  1. Chang Y, Liu H, Liu M, Liao X, Sahu SK, Fu Y, et al.
    Gigascience, 2019 03 01;8(3).
    PMID: 30535374 DOI: 10.1093/gigascience/giy152
    BACKGROUND: The expanding world population is expected to double the worldwide demand for food by 2050. Eighty-eight percent of countries currently face a serious burden of malnutrition, especially in Africa and south and southeast Asia. About 95% of the food energy needs of humans are fulfilled by just 30 species, of which wheat, maize, and rice provide the majority of calories. Therefore, to diversify and stabilize the global food supply, enhance agricultural productivity, and tackle malnutrition, greater use of neglected or underutilized local plants (so-called orphan crops, but also including a few plants of special significance to agriculture, agroforestry, and nutrition) could be a partial solution.

    RESULTS: Here, we present draft genome information for five agriculturally, biologically, medicinally, and economically important underutilized plants native to Africa: Vigna subterranea, Lablab purpureus, Faidherbia albida, Sclerocarya birrea, and Moringa oleifera. Assembled genomes range in size from 217 to 654 Mb. In V. subterranea, L. purpureus, F. albida, S. birrea, and M. oleifera, we have predicted 31,707, 20,946, 28,979, 18,937, and 18,451 protein-coding genes, respectively. By further analyzing the expansion and contraction of selected gene families, we have characterized root nodule symbiosis genes, transcription factors, and starch biosynthesis-related genes in these genomes.

    CONCLUSIONS: These genome data will be useful to identify and characterize agronomically important genes and understand their modes of action, enabling genomics-based, evolutionary studies, and breeding strategies to design faster, more focused, and predictable crop improvement programs.

  2. Zhao H, Zhao S, International Network for Bamboo and Rattan, Fei B, Liu H, Yang H, et al.
    Gigascience, 2017 07 01;6(7):1-7.
    PMID: 28637269 DOI: 10.1093/gigascience/gix046
    Bamboo and rattan are widely grown for manufacturing, horticulture, and agroforestry. Bamboo and rattan production might help reduce poverty, boost economic growth, mitigate climate change, and protect the natural environment. Despite progress in research, sufficient molecular and genomic resources to study these species are lacking. We launched the Genome Atlas of Bamboo and Rattan (GABR) project, a comprehensive, coordinated international effort to accelerate understanding of bamboo and rattan genetics through genome analysis. GABR includes 2 core subprojects: Bamboo-T1K (Transcriptomes of 1000 Bamboos) and Rattan-G5 (Genomes of 5 Rattans), and several other subprojects. Here we describe the organization, directions, and status of GABR.
  3. Tunkl C, Agarwal A, Ramage E, Velez FS, Roushdy T, Ullberg T, et al.
    Int J Stroke, 2024 Nov 15.
    PMID: 39460528 DOI: 10.1177/17474930241298450
    BACKGROUND: Despite the proven efficacy of telestroke in improving clinical outcomes by providing access to specialized expertise and allowing rapid expert hyperacute stroke management and decision-making, detailed operational evidence is scarce, especially for less developed or lower income regions.

    AIM: We aimed to map the global telestroke landscape and characterize existing networks.

    METHODS: We employed a four-tiered approach to comprehensively identify telestroke networks, primarily involving engagement with national stroke experts, stroke societies, and international stroke authorities. A carefully designed questionnaire was then distributed to the leaders of all identified networks to assess these networks' structures, processes, and outcomes.

    RESULTS: We identified 254 telestroke networks distributed across 67 countries. High-income countries (HICs) concentrated 175 (69%) of the networks. No evidence of telestroke services was found in 58 (30%) countries. From the identified networks, 88 (34%) completed the survey, being 61 (71%) located in HICs. Network setup was highly heterogeneous, ranging from 17 (22%) networks with more than 20 affiliated hospitals, providing thousands of annual consultations using purpose-built highly specialized technology, to 11 (13%) networks with fewer than 120 consultations annually using generic videoconferencing equipment. Real-time video and image transfer was employed in 64 (75%) networks, while 62 (74%) conducting quality monitoring. Most networks established in the past 3 years were located in low- and middle-income countries (LMICs).

    CONCLUSION: This comprehensive global survey of telestroke networks found significant variation in network coverage, setup, and technology use. Most services are in HICs, and a few services are in LMICs, although an emerging trend of new networks in these regions marks a pivotal moment in global telestroke care. The wide variation in quality monitoring practices across networks, with many failing to report key performance metrics, underscores the urgent need for standardized, resource-appropriate, quality assurance measures that can be adapted to diverse settings.

  4. Narayanan KB, Ali M, Barclay BJ, Cheng QS, D'Abronzo L, Dornetshuber-Fleiss R, et al.
    Carcinogenesis, 2015 Jun;36 Suppl 1:S89-110.
    PMID: 26106145 DOI: 10.1093/carcin/bgv032
    Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically, the up-regulation of pro-survival factors, including oncogenic factors and antiapoptotic signaling pathways, and the down-regulation of pro-apoptotic factors, including tumor suppressive factors, confers resistance to cell death in tumor cells, which supports the emergence of a fully immortalized cellular phenotype. This review considers the potential relevance of ubiquitous environmental chemical exposures that have been shown to disrupt key pathways and mechanisms associated with this sort of dysfunction. Specifically, bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor and oxyfluorfen are discussed as prototypical chemical disruptors; as their effects relate to resistance to cell death, as constituents within environmental mixtures and as potential contributors to environmental carcinogenesis.
  5. Lawrenson K, Song F, Hazelett DJ, Kar SP, Tyrer J, Phelan CM, et al.
    Gynecol Oncol, 2019 05;153(2):343-355.
    PMID: 30898391 DOI: 10.1016/j.ygyno.2019.02.023
    OBJECTIVE: Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women.

    METHODS: Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations.

    RESULTS: At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 × 10-9) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 × 10-9). SNP rs6902488 at 6p25.2 (r2 = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP <10%). At chromosome 20q11.22, rs74272064 was associated with HGSOC risk (OR = 1.27, P = 9.0 × 10-8). Overall EOC risk was associated with rs10260419 at chromosome 7p21.3 (OR = 1.33, P = 1.2 × 10-7) and rs74917072 at chromosome 2q37.3 (OR = 1.25, P = 4.7 × 10-7). At 2q37.3, expression quantitative trait locus analysis in 404 HGSOC tissues identified ESPNL as a putative candidate susceptibility gene (P = 1.2 × 10-7).

    CONCLUSION: While some risk loci were shared between East Asian and European populations, others were population-specific, indicating that the landscape of EOC risk in Asian women has both shared and unique features compared to women of European ancestry.

  6. Dixon JM, Weerahewa J, Hellin J, Rola-Rubzen MF, Huang J, Kumar S, et al.
    Agric Syst, 2021 Oct;193:103168.
    PMID: 36284566 DOI: 10.1016/j.agsy.2021.103168
    CONTEXT: The COVID-19 pandemic has been affecting health and economies across the world, although the nature of direct and indirect effects on Asian agrifood systems and food security has not yet been well understood.

    OBJECTIVES: This paper assesses the initial responses of major farming and food systems to COVID-19 in 25 Asian countries, and considers the implications for resilience, food and nutrition security and recovery policies by the governments.

    METHODS: A conceptual systems model was specified including key pathways linking the direct and indirect effects of COVID-19 to the resilience and performance of the four principal Asian farming and food systems, viz, lowland rice based; irrigated wheat based; hill mixed; and dryland mixed systems. Based on this framework, a systematic survey of 2504 key informants (4% policy makers, 6% researchers or University staff, 6% extension workers, 65% farmers, and 19% others) in 20 Asian countries was conducted and the results assessed and analysed.

    RESULTS AND CONCLUSION: The principal Asian farming and food systems were moderately resilient to COVID-19, reinforced by government policies in many countries that prioritized food availability and affordability. Rural livelihoods and food security were affected primarily because of disruptions to local labour markets (especially for off-farm work), farm produce markets (notably for perishable foods) and input supply chains (i.e., seeds and fertilisers). The overall effects on system performance were most severe in the irrigated wheat based system and least severe in the hill mixed system, associated in the latter case with greater resilience and diversification and less dependence on external inputs and long market chains. Farming and food systems' resilience and sustainability are critical considerations for recovery policies and programmes, especially in relation to economic performance that initially recovered more slowly than productivity, natural resources status and social capital. Overall, the resilience of Asian farming and food systems was strong because of inherent systems characteristics reinforced by public policies that prioritized staple food production and distribution as well as complementary welfare programmes. With the substantial risks to plant- and animal-sourced food supplies from future zoonoses and the institutional vulnerabilities revealed by COVID-19, efforts to improve resilience should be central to recovery programmes.

    SIGNIFICANCE: This study was the first Asia-wide systems assessment of the effects of COVID-19 on agriculture and food systems, differentiating the effects of the pandemic across the four principal regional farming and food systems in the region.

  7. Ho WK, Tai MC, Dennis J, Shu X, Li J, Ho PJ, et al.
    Genet Med, 2022 Mar;24(3):586-600.
    PMID: 34906514 DOI: 10.1016/j.gim.2021.11.008
    PURPOSE: Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups.

    METHODS: The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases).

    RESULTS: The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk.

    CONCLUSION: PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry.

  8. Papadimitriou N, Dimou N, Tsilidis KK, Banbury B, Martin RM, Lewis SJ, et al.
    Nat Commun, 2020 01 30;11(1):597.
    PMID: 32001714 DOI: 10.1038/s41467-020-14389-8
    Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers.
  9. Fulsom BG, Pedlar TK, Adachi I, Aihara H, Al Said S, Asner DM, et al.
    Phys Rev Lett, 2018 Dec 07;121(23):232001.
    PMID: 30576207 DOI: 10.1103/PhysRevLett.121.232001
    We report the observation of ϒ(2S)→γη_{b}(1S) decay based on an analysis of the inclusive photon spectrum of 24.7  fb^{-1} of e^{+}e^{-} collisions at the ϒ(2S) center-of-mass energy collected with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We measure a branching fraction of B[ϒ(2S)→γη_{b}(1S)]=(6.1_{-0.7-0.6}^{+0.6+0.9})×10^{-4} and derive an η_{b}(1S) mass of 9394.8_{-3.1-2.7}^{+2.7+4.5}  MeV/c^{2}, where the uncertainties are statistical and systematic, respectively. The significance of our measurement is greater than 7 standard deviations, constituting the first observation of this decay mode.
  10. Li YB, Shen CP, Yuan CZ, Adachi I, Aihara H, Al Said S, et al.
    Phys Rev Lett, 2019 Mar 01;122(8):082001.
    PMID: 30932568 DOI: 10.1103/PhysRevLett.122.082001
    We present the first measurements of absolute branching fractions of Ξ_{c}^{0} decays into Ξ^{-}π^{+}, ΛK^{-}π^{+}, and pK^{-}K^{-}π^{+} final states. The measurements are made using a dataset comprising (772±11)×10^{6} BB[over ¯] pairs collected at the ϒ(4S) resonance with the Belle detector at the KEKB e^{+}e^{-} collider. We first measure the absolute branching fraction for B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0} using a missing-mass technique; the result is B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})=(9.51±2.10±0.88)×10^{-4}. We subsequently measure the product branching fractions B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→Ξ^{-}π^{+}), B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→ΛK^{-}π^{+}), and B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+}) with improved precision. Dividing these product branching fractions by the result for B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0} yields the following branching fractions: B(Ξ_{c}^{0}→Ξ^{-}π^{+})=(1.80±0.50±0.14)%, B(Ξ_{c}^{0}→ΛK^{-}π^{+})=(1.17±0.37±0.09)%, and B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+})=(0.58±0.23±0.05)%. For the above branching fractions, the first uncertainties are statistical and the second are systematic. Our result for B(Ξ_{c}^{0}→Ξ^{-}π^{+}) can be combined with Ξ_{c}^{0} branching fractions measured relative to Ξ_{c}^{0}→Ξ^{-}π^{+} to yield other absolute Ξ_{c}^{0} branching fractions.
  11. Seong IS, Vahsen SE, Adachi I, Aihara H, Al Said S, Asner DM, et al.
    Phys Rev Lett, 2019 Jan 11;122(1):011801.
    PMID: 31012694 DOI: 10.1103/PhysRevLett.122.011801
    We report on the first Belle search for a light CP-odd Higgs boson, A^{0}, that decays into low mass dark matter, χ, in final states with a single photon and missing energy. We search for events produced via the dipion transition ϒ(2S)→ϒ(1S)π^{+}π^{-}, followed by the on-shell process ϒ(1S)→γA^{0} with A^{0}→χχ, or by the off-shell process ϒ(1S)→γχχ. Utilizing a data sample of 157.3×10^{6} ϒ(2S) decays, we find no evidence for a signal. We set limits on the branching fractions of such processes in the mass ranges M_{A^{0}}<8.97  GeV/c^{2} and M_{χ}<4.44  GeV/c^{2}. We then use the limits on the off-shell process to set competitive limits on WIMP-nucleon scattering in the WIMP mass range below 5  GeV/c^{2}.
  12. Sibidanov A, Varvell KE, Adachi I, Aihara H, Al Said S, Asner DM, et al.
    Phys Rev Lett, 2018 Jul 20;121(3):031801.
    PMID: 30085771 DOI: 10.1103/PhysRevLett.121.031801
    We report the results of a search for the rare, purely leptonic decay B^{-}→μ^{-}ν[over ¯]_{μ} performed with a 711  fb^{-1} data sample that contains 772×10^{6}  BB[over ¯] pairs, collected near the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The signal events are selected based on the presence of a high momentum muon and the topology of the rest of the event showing properties of a generic B-meson decay, as well as the missing energy and momentum being consistent with the hypothesis of a neutrino from the signal decay. We find a 2.4 standard deviation excess above background including systematic uncertainties, which corresponds to a branching fraction of B(B^{-}→μ^{-}ν[over ¯]_{μ})=(6.46±2.22±1.60)×10^{-7} or a frequentist 90% confidence level interval on the B^{-}→μ^{-}ν[over ¯]_{μ} branching fraction of [2.9,10.7]×10^{-7}.
  13. Guido E, Mussa R, Tamponi U, Aihara H, Al Said S, Asner DM, et al.
    Phys Rev Lett, 2018 Aug 10;121(6):062001.
    PMID: 30141661 DOI: 10.1103/PhysRevLett.121.062001
    We report the first observation of the hadronic transition ϒ(4S)→η^{'}ϒ(1S), using 496  fb^{-1} data collected at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We reconstruct the η^{'} meson through its decays to ρ^{0}γ and to π^{+}π^{-}η, with η→γγ. We measure B(ϒ(4S)→η^{'}ϒ(1S))=[3.43±0.88(stat)±0.21(syst)]×10^{-5}, with a significance of 5.7σ.
  14. Guan Y, Vossen A, Adachi I, Adamczyk K, Ahn JK, Aihara H, et al.
    Phys Rev Lett, 2019 Feb 01;122(4):042001.
    PMID: 30768311 DOI: 10.1103/PhysRevLett.122.042001
    We report the first observation of the spontaneous polarization of Λ and Λ[over ¯] hyperons transverse to the production plane in e^{+}e^{-} annihilation, which is attributed to the effect arising from a polarizing fragmentation function. For inclusive Λ/Λ[over ¯] production, we also report results with subtracted feed-down contributions from Σ^{0} and charm. This measurement uses a dataset of 800.4  fb^{-1} collected by the Belle experiment at or near a center-of-mass energy of 10.58 GeV. We observe a significant polarization that rises with the fractional energy carried by the Λ/Λ[over ¯] hyperon.
  15. Seyed Khoei N, Jenab M, Murphy N, Banbury BL, Carreras-Torres R, Viallon V, et al.
    BMC Med, 2020 09 03;18(1):229.
    PMID: 32878631 DOI: 10.1186/s12916-020-01703-w
    BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.

    METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P 

  16. Ji F, Tran S, Ogawa E, Huang CF, Suzuki T, Wong YJ, et al.
    J Clin Transl Hepatol, 2024 Jul 28;12(7):646-658.
    PMID: 38993510 DOI: 10.14218/JCTH.2024.00089
    BACKGROUND AND AIMS: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6.

    METHODS: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021.

    RESULTS: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12.

    CONCLUSIONS: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%).

  17. Goodson WH, Lowe L, Carpenter DO, Gilbertson M, Manaf Ali A, Lopez de Cerain Salsamendi A, et al.
    Carcinogenesis, 2015 Jun;36 Suppl 1:S254-96.
    PMID: 26106142 DOI: 10.1093/carcin/bgv039
    Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.
  18. Dareng EO, Coetzee SG, Tyrer JP, Peng PC, Rosenow W, Chen S, et al.
    Am J Hum Genet, 2024 May 07.
    PMID: 38723632 DOI: 10.1016/j.ajhg.2024.04.011
    To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10-8) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10-5). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate <0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study.
  19. Adachi I, Adye T, Ahmed H, Ahn JK, Aihara H, Akar S, et al.
    Phys Rev Lett, 2018 Dec 28;121(26):261801.
    PMID: 30636113 DOI: 10.1103/PhysRevLett.121.261801
    We present first evidence that the cosine of the CP-violating weak phase 2β is positive, and hence exclude trigonometric multifold solutions of the Cabibbo-Kobayashi-Maskawa (CKM) Unitarity Triangle using a time-dependent Dalitz plot analysis of B^{0}→D^{(*)}h^{0} with D→K_{S}^{0}π^{+}π^{-} decays, where h^{0}∈{π^{0},η,ω} denotes a light unflavored and neutral hadron. The measurement is performed combining the final data sets of the BABAR and Belle experiments collected at the ϒ(4S) resonance at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain (471±3)×10^{6}BB[over ¯] pairs recorded by the BABAR detector and (772±11)×10^{6}BB[over ¯] pairs recorded by the Belle detector. The results of the measurement are sin2β=0.80±0.14(stat)±0.06(syst)±0.03(model) and cos2β=0.91±0.22(stat)±0.09(syst)±0.07(model). The result for the direct measurement of the angle β of the CKM Unitarity Triangle is β=[22.5±4.4(stat)±1.2(syst)±0.6(model)]°. The measurement assumes no direct CP violation in B^{0}→D^{(*)}h^{0} decays. The quoted model uncertainties are due to the composition of the D^{0}→K_{S}^{0}π^{+}π^{-} decay amplitude model, which is newly established by performing a Dalitz plot amplitude analysis using a high-statistics e^{+}e^{-}→cc[over ¯] data sample. CP violation is observed in B^{0}→D^{(*)}h^{0} decays at the level of 5.1 standard deviations. The significance for cos2β>0 is 3.7 standard deviations. The trigonometric multifold solution π/2-β=(68.1±0.7)° is excluded at the level of 7.3 standard deviations. The measurement resolves an ambiguity in the determination of the apex of the CKM Unitarity Triangle.
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