Showing papers by "Hiroshima University published in 2020"
TL;DR: The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.
1,600 citations
TL;DR: The extent of the trait data compiled in TRY is evaluated and emerging patterns of data coverage and representativeness are analyzed to conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements.
Abstract: Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
882 citations
TL;DR: Overall, existing knowledge shows that the COVID-19 crisis entails an excellent opportunity for planners and policy makers to take transformative actions towards creating cities that are more just, resilient, and sustainable.
610 citations
Max Planck Society1, University of Turin2, Technical University of Denmark3, Curtin University4, Utrecht University5, Dalian Institute of Chemical Physics6, Korea Institute of Science and Technology7, University of Paris8, University of Oxford9, Rutherford Appleton Laboratory10, Université catholique de Louvain11, University of Crete12, University of Nottingham13, Griffith University14, Aarhus University15, Tohoku University16, Hiroshima University17, Kyushu University18, University of the Western Cape19, Stockholm University20, University of Bologna21, University of Southern Denmark22, National Institute of Standards and Technology23
TL;DR: In this article, the authors present a review of the development of hydrogen storage materials, methods and techniques, including electrochemical and thermal storage systems, and an outlook for future prospects and research on hydrogen-based energy storage.
439 citations
TL;DR: The present recommendations provide guidance on kinetic analysis of multi-step processes as measured by thermal analysis methods such as thermogravimetry and differential scanning calorimetry.
395 citations
Kindai University1, Kurume University2, Hiroshima University3, Yamaguchi University4, Nagoya City University5, Kawasaki Medical School6, Nagoya University7, Jichi Medical University8, Kyoto Prefectural University of Medicine9, Kagoshima University10, Fujita Health University11, Nagasaki University12, Chiba University13, Kyorin University14, Memorial Hospital of South Bend15, University of Liverpool16
TL;DR: TACE plus sorafenib significantly improved PFS over TACE alone in patients with unresectable HCC, and Adverse events were consistent with those of previous TACE combination trials.
Abstract: Objective This trial compared the efficacy and safety of transarterial chemoembolisation (TACE) plus sorafenib with TACE alone using a newly established TACE-specific endpoint and pre-treatment of sorafenib before initial TACE. Design Patients with unresectable hepatocellular carcinoma (HCC) were randomised to TACE plus sorafenib (n=80) or TACE alone (n=76). Patients in the combination group received sorafenib 400 mg once daily for 2–3 weeks before TACE, followed by 800 mg once daily during on-demand conventional TACE sessions until time to untreatable (unTACEable) progression (TTUP), defined as untreatable tumour progression, transient deterioration to Child-Pugh C or appearance of vascular invasion/extrahepatic spread. Co-primary endpoints were progression-free survival (PFS), which is not a conventional one but defined as TTUP, or time to any cause of death plus overall survival (OS). Multiplicity was adjusted by gatekeeping hierarchical testing. Results Median PFS was significantly longer in the TACE plus sorafenib than in the TACE alone group (25.2 vs 13.5 months; p=0.006). OS was not analysed because only 73.6% of OS events were reached. Median TTUP (26.7 vs 20.6 months; p=0.02) was also significantly longer in the TACE plus sorafenib group. OS at 1 year and 2 years in TACE plus sorafenib group and TACE alone group were 96.2% and 82.7% and 77.2% and 64.6%, respectively. There were no unexpected toxicities. Conclusion TACE plus sorafenib significantly improved PFS over TACE alone in patients with unresectable HCC. Adverse events were consistent with those of previous TACE combination trials. Trial registration number NCT01217034.
341 citations
TL;DR: These findings not only help to explain the poor interferon response in COVID-19 patients, but also describe the emergence of natural SARS-CoV-2 quasispecies with an extended ORF3b gene that may potentially affect CO VID-19 pathogenesis.
332 citations
Kyoto University1, Hospital General Universitario Gregorio Marañón2, Fudan University3, Harbin Medical University4, Sarah Cannon Research Institute5, Yonsei University6, University of Padua7, Hiroshima University8, Mater Health Services9, Universitaire Ziekenhuizen Leuven10, University of Ulm11, University of Manchester12, Harvard University13, Trakya University14, Eli Lilly and Company15, Baylor University Medical Center16, University of Pittsburgh17
TL;DR: Abemaciclib when combined with ET is the first CDK4/6 inhibitor to demonstrate a significant improvement in IDFS in patients with HR+, HER2− node-positive EBC at high risk of early recurrence.
Abstract: PURPOSEMany patients with HR+, HER2− early breast cancer (EBC) will not experience recurrence or have distant recurrence with currently available standard therapies. However, up to 30% of patients ...
290 citations
TL;DR: This study trained convolutional neural networks and recurrent neural networks on biopsy histopathology whole-slide images of stomach and colon to classify WSI into adenocarcinoma, adenoma, and non-neoplastic.
Abstract: Histopathological classification of gastric and colonic epithelial tumours is one of the routine pathological diagnosis tasks for pathologists. Computational pathology techniques based on Artificial intelligence (AI) would be of high benefit in easing the ever increasing workloads on pathologists, especially in regions that have shortages in access to pathological diagnosis services. In this study, we trained convolutional neural networks (CNNs) and recurrent neural networks (RNNs) on biopsy histopathology whole-slide images (WSIs) of stomach and colon. The models were trained to classify WSI into adenocarcinoma, adenoma, and non-neoplastic. We evaluated our models on three independent test sets each, achieving area under the curves (AUCs) up to 0.97 and 0.99 for gastric adenocarcinoma and adenoma, respectively, and 0.96 and 0.99 for colonic adenocarcinoma and adenoma respectively. The results demonstrate the generalisation ability of our models and the high promising potential of deployment in a practical histopathological diagnostic workflow system.
268 citations
TL;DR: This work systematically explore the phylogeny of taxa currently assigned to these classes using 120 conserved single-copy marker genes as well as rRNA genes and indicates the independent acquisition of predatory behaviour in the phyla Myxococcota and Bdellovibrio, which is consistent with their distinct modes of action.
Abstract: The class Deltaproteobacteria comprises an ecologically and metabolically diverse group of bacteria best known for dissimilatory sulphate reduction and predatory behaviour. Although this lineage is the fourth described class of the phylum Proteobacteria, it rarely affiliates with other proteobacterial classes and is frequently not recovered as a monophyletic unit in phylogenetic analyses. Indeed, one branch of the class Deltaproteobacteria encompassing Bdellovibrio-like predators was recently reclassified into a separate proteobacterial class, the Oligoflexia. Here we systematically explore the phylogeny of taxa currently assigned to these classes using 120 conserved single-copy marker genes as well as rRNA genes. The overwhelming majority of markers reject the inclusion of the classes Deltaproteobacteria and Oligoflexia in the phylum Proteobacteria. Instead, the great majority of currently recognized members of the class Deltaproteobacteria are better classified into four novel phylum-level lineages. We propose the names Desulfobacterota phyl. nov. and Myxococcota phyl. nov. for two of these phyla, based on the oldest validly published names in each lineage, and retain the placeholder name SAR324 for the third phylum pending formal description of type material. Members of the class Oligoflexia represent a separate phylum for which we propose the name Bdellovibrionota phyl. nov. based on priority in the literature and general recognition of the genus Bdellovibrio. Desulfobacterota phyl. nov. includes the taxa previously classified in the phylum Thermodesulfobacteria, and these reclassifications imply that the ability of sulphate reduction was vertically inherited in the Thermodesulfobacteria rather than laterally acquired as previously inferred. Our analysis also indicates the independent acquisition of predatory behaviour in the phyla Myxococcota and Bdellovibrionota, which is consistent with their distinct modes of action. This work represents a stable reclassification of one of the most taxonomically challenging areas of the bacterial tree and provides a robust framework for future ecological and systematic studies.
252 citations
Harvard University1, Broad Institute2, Kyushu University3, Chiba University4, University of Tokyo5, Osaka University6, University of North Carolina at Chapel Hill7, Japanese Foundation for Cancer Research8, Tokyo Medical and Dental University9, Tohoku University10, National Cancer Research Institute11, Fujita Health University12, Hiroshima University13, Shiga University of Medical Science14, University of Tokushima15, Kyoto University16, Iwate Medical University17, Nagoya University18, Nippon Medical School19, Nihon University20, Juntendo University21, University of Hyogo22, Saga University23, University of Manchester24
TL;DR: A large-scale genome-wide association study in a Japanese population provides insights into the etiology of complex diseases and highlights the importance of performing GWAS in non-European populations.
Abstract: The overwhelming majority of participants in current genetic studies are of European ancestry. To elucidate disease biology in the East Asian population, we conducted a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 320 independent signals in 276 loci for 27 diseases, with 25 novel loci (P < 9.58 × 10-9). East Asian-specific missense variants were identified as candidate causal variants for three novel loci, and we successfully replicated two of them by analyzing independent Japanese cohorts; p.R220W of ATG16L2 (associated with coronary artery disease) and p.V326A of POT1 (associated with lung cancer). We further investigated enrichment of heritability within 2,868 annotations of genome-wide transcription factor occupancy, and identified 378 significant enrichments across nine diseases (false discovery rate < 0.05) (for example, NKX3-1 for prostate cancer). This large-scale GWAS in a Japanese population provides insights into the etiology of complex diseases and highlights the importance of performing GWAS in non-European populations.
TL;DR: The 4LAC catalog of active galactic nuclei (AGNs) detected by the Fermi Gamma-ray Space Telescope Large Area Telescope (4LAC) between 2008 August 4 and 2016 August 2 contains 2863 objects located at high Galactic latitudes (|b|>10°deg}).
Abstract: The fourth catalog of active galactic nuclei (AGNs) detected by the Fermi Gamma-ray Space Telescope Large Area Telescope (4LAC) between 2008 August 4 and 2016 August 2 contains 2863 objects located at high Galactic latitudes (|b|>10{\deg}). It includes 85% more sources than the previous 3LAC catalog based on 4 years of data. AGNs represent at least 79% of the high-latitude sources in the fourth Fermi-Large Area Telescope Source Catalog (4FGL), which covers the energy range from 50 MeV to 1 TeV. In addition, 344 gamma-ray AGNs are found at low Galactic latitudes. Most of the 4LAC AGNs are blazars (98%), while the remainder are other types of AGNs. The blazar population consists of 24% Flat Spectrum Radio Quasars (FSRQs), 38% BL Lac-type objects (BL Lacs), and 38% blazar candidates of unknown types (BCUs). On average, FSRQs display softer spectra and stronger variability in the gamma-ray band than BL Lacs do, confirming previous findings. All AGNs detected by ground-based atmospheric Cherenkov telescopes are also found in the 4LAC.
TL;DR: This review summarizes currently available information on the regulation of the intestinal TJ barrier by food components and suggests that tight junctions in intestinal epithelial cells could be regulated, as a potential target, by dietary factors to prevent and reduce different inflammatory disorders.
Abstract: Tight junctions (TJs) play an important role in intestinal barrier function. TJs in intestinal epithelial cells are composed of different junctional molecules, such as claudin and occludin, and regulate the paracellular permeability of water, ions, and macromolecules in adjacent cells. One of the most important roles of the TJ structure is to provide a physical barrier to luminal inflammatory molecules. Impaired integrity and structure of the TJ barrier result in a forcible activation of immune cells and chronic inflammation in different tissues. According to recent studies, the intestinal TJ barrier could be regulated, as a potential target, by dietary factors to prevent and reduce different inflammatory disorders, although the precise mechanisms underlying the dietary regulation remain unclear. This review summarizes currently available information on the regulation of the intestinal TJ barrier by food components.
TL;DR: It is revealed that CO2 emissions have a negative long-run relationship with trade exclusively for developed countries, while they have a positive long- run relationship with FDI inflows solely for developing countries.
TL;DR: Assessment of how public health restrictions impact PA, subjective well-being (SWB), and health-related quality of life (HRQoL) of community-dwelling elderly found decreased PA was strongly associated with lower SWB.
Abstract: Psychological distress caused by decreased physical activity (PA) is a growing concern among the elderly due to public health measures since the coronavirus disease (COVID-19). We aimed to (1) assess how public health restrictions impact PA, subjective well-being (SWB), and health-related quality of life (HRQoL) of community-dwelling elderly, and (2) investigate risk factors that lead to a decline in PA. Self-administered questionnaires assessed the changes in PA, SWB, HRQoL. Multivariate logistic regression analysis was performed to identify significant associated risk factors for decreased PA. Of 165 participants (valid response rate, 41.3%; mean age, 78.5 ± 8.0 years), 47.3% became less active, 23.0% became more active, and 29.7% maintained PA levels. There was a significant decrease in SWB at baseline and follow-up after COVID-19 restrictions in the less active group (p < 0.01). Higher levels of moderate or strenuous exercise/sports activity at baseline (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.01-1.24), and lower mental component HRQoL scores at baseline (OR, 0.96; 95% CI, 0.93-0.99) were associated with an increased risk of decreased PA. Public health restrictions impact the PA of the elderly, especially those who had higher levels of exercise/sports activity and lower HRQoL before COVID-19. Decreased PA was strongly associated with lower SWB.
TL;DR: It is shown analytically that spacetimes that deviate from the Kerr metric but satisfy weak-field tests can lead to large deviations in the predicted black-hole shadows that are inconsistent with even the current EHT measurements.
Abstract: The 2017 Event Horizon Telescope (EHT) observations of the central source in M87 have led to the first measurement of the size of a black-hole shadow. This observation offers a new and clean gravitational test of the black-hole metric in the strong-field regime. We show analytically that spacetimes that deviate from the Kerr metric but satisfy weak-field tests can lead to large deviations in the predicted black-hole shadows that are inconsistent with even the current EHT measurements. We use numerical calculations of regular, parametric, non-Kerr metrics to identify the common characteristic among these different parametrizations that control the predicted shadow size. We show that the shadow-size measurements place significant constraints on deviation parameters that control the second post-Newtonian and higher orders of each metric and are, therefore, inaccessible to weak-field tests. The new constraints are complementary to those imposed by observations of gravitational waves from stellar-mass sources.
Cornell University1, Kanazawa University2, University of Zurich3, University of Cambridge4, University of Toulouse5, University of Arizona6, University of Marburg7, University of Leeds8, Polytechnic University of Valencia9, University of Göttingen10, University of Düsseldorf11, University of Bristol12, Boyce Thompson Institute for Plant Research13, University of California, Davis14, Wageningen University and Research Centre15, University of Bonn16, Hiroshima University17, University of Freiburg18, Smithsonian Institution19, Laval University20, University of Münster21, University of Alberta22, Rikkyo University23
TL;DR: High-quality genomes of Anthoceros hornworts are provided and candidate genes involved in cyanobacterial symbiosis are identified and found that LCIB, a Chlamydomonas CCM gene, is present in hornwort but absent in other plant lineages, implying a possible conserved role in CCM function.
Abstract: Hornworts comprise a bryophyte lineage that diverged from other extant land plants >400 million years ago and bears unique biological features, including a distinct sporophyte architecture, cyanobacterial symbiosis and a pyrenoid-based carbon-concentrating mechanism (CCM). Here, we provide three high-quality genomes of Anthoceros hornworts. Phylogenomic analyses place hornworts as a sister clade to liverworts plus mosses with high support. The Anthoceros genomes lack repeat-dense centromeres as well as whole-genome duplication, and contain a limited transcription factor repertoire. Several genes involved in angiosperm meristem and stomatal function are conserved in Anthoceros and upregulated during sporophyte development, suggesting possible homologies at the genetic level. We identified candidate genes involved in cyanobacterial symbiosis and found that LCIB, a Chlamydomonas CCM gene, is present in hornworts but absent in other plant lineages, implying a possible conserved role in CCM function. We anticipate that these hornwort genomes will serve as essential references for future hornwort research and comparative studies across land plants.
TL;DR: Pesticide adsorption onto low-cost materials can effectively remediate contaminated waters and nanoparticle adsorbent and carbon-based adsorbents exhibit high performance in removing pesticides from water bodies.
TL;DR: The results suggest that rituximab could be useful maintenance therapy for individuals with NMOSD who are AQP4 antibody-positive, and this study is limited by its small sample size and inclusion of participants with mild disease activity.
Abstract: Summary Background Pharmacological prevention against relapses in patients with neuromyelitis optica spectrum disorder (NMOSD) is developing rapidly. We aimed to investigate the safety and efficacy of rituximab, an anti-CD20 monoclonal antibody, against relapses in patients with NMOSD. Methods We did a multicentre, randomised, double-blind, placebo-controlled clinical trial at eight hospitals in Japan. Patients aged 16–80 years with NMOSD who were seropositive for aquaporin 4 (AQP4) antibody, were taking 5–30 mg/day oral steroids, and had an Expanded Disability Status Scale (EDSS) score of 7·0 or less were eligible for the study. Individuals taking any other immunosuppressants were excluded. Participants were randomly allocated (1:1) either rituximab or placebo by a computer-aided dynamic random allocation system. The doses of concomitant steroid (converted to equivalent doses of prednisolone) and relapses in previous 2 years were set as stratification factors. Participants and those assessing outcomes were unaware of group assignments. Rituximab (375 mg/m2) was administered intravenously every week for 4 weeks, then 6-month interval dosing was done (1000 mg every 2 weeks, at 24 weeks and 48 weeks after randomisation). A matching placebo was administered intravenously. Concomitant oral prednisolone was gradually reduced to 2–5 mg/day, according to the protocol. The primary outcome was time to first relapse within 72 weeks. Relapses were defined as patient-reported symptoms or any new signs consistent with CNS lesions and attributable objective changes in MRI or visual evoked potential. The primary analysis was done in the full analysis set (all randomly assigned patients) and safety analyses were done in the safety analysis set (all patients who received at least one infusion of assigned treatment). The primary analysis was by intention-to-treat principles. This trial is registered with the UMIN clinical trial registry, UMIN000013453. Findings Between May 10, 2014, and Aug 15, 2017, 38 participants were recruited and randomly allocated either rituximab (n=19) or placebo (n=19). Three (16%) patients assigned rituximab discontinued the study and were analysed as censored cases. Seven (37%) relapses occurred in patients allocated placebo and none were recorded in patients assigned rituximab (group difference 36·8%, 95% CI 12·3–65·5; log-rank p=0·0058). Eight serious adverse events were recorded, four events in three (16%) patients assigned rituximab (lumbar compression fracture and infection around nail of right foot [n=1], diplopia [n=1], and uterine cancer [n=1]) and four events in two (11%) people allocated to placebo (exacerbation of glaucoma and bleeding in the right eye chamber after surgery [n=1], and visual impairment and asymptomatic white matter brain lesion on MRI [n=1]); all patients recovered. No deaths were reported. Interpretation Rituximab prevented relapses for 72 weeks in patients with NMOSD who were AQP4 antibody-positive. This study is limited by its small sample size and inclusion of participants with mild disease activity. However, our results suggest that rituximab could be useful maintenance therapy for individuals with NMOSD who are AQP4 antibody-positive. Funding Japanese Ministry of Health, Labour and Welfare, Japan Agency for Medical Research and Development, and Zenyaku Kogyo.
TL;DR: This study undertook this study to prospectively evaluate the efficacy and safety of a combined immunosuppressive regimen for anti–MDA‐5–positive DM patients with ILD.
Abstract: OBJECTIVE Interstitial lung disease (ILD) accompanied by anti-melanoma differentiation-associated gene 5 (anti-MDA-5)-positive dermatomyositis (DM) is often rapidly progressive and associated with poor prognosis. Because there is no established treatment, we undertook this study to prospectively evaluate the efficacy and safety of a combined immunosuppressive regimen for anti-MDA-5-positive DM patients with ILD. METHODS Adult Japanese patients with new-onset anti-MDA-5-positive DM with ILD (n = 29) were enrolled at multiple study centers from 2014 to 2017. They were treated with a regimen of high-dose glucocorticoids (GCs), tacrolimus, and intravenous cyclophosphamide (IV CYC). Plasmapheresis was used if a patient's condition worsened after the regimen started. The primary end point was 6-month survival, which was compared between this group of patients and a historical control group (n = 15) consisting of anti-MDA-5-positive DM patients with ILD who received step-up treatment (high-dose GC and stepwise addition of immunosuppressant). Secondary end points were 12-month survival rate, adverse events, and changes in laboratory data. RESULTS The combined immunosuppressive regimen group showed significantly higher 6-month survival rates than the step-up treatment group (89% versus 33%; P < 0.0001). Over a period of 52 weeks, improvements in anti-MDA-5 titers, serum ferritin levels, vital capacity, and chest high-resolution computed tomography scores were observed. The combined immunosuppressive regimen group received IV CYC nearly 20 days earlier with shorter intervals and tended to receive plasmapheresis more often than patients undergoing step-up treatment. Cytomegalovirus reactivation was frequently observed over 52 weeks. CONCLUSION A combined immunosuppressive regimen is effective for anti-MDA-5-positive DM patients with ILD. Plasmapheresis can be used for additional effect in intractable disease. Patients should be carefully monitored for opportunistic infections during treatment.
Kyushu University1, University of Tokyo2, Chiba University3, Seoul National University4, Kansai Medical University5, Kyoto University6, Kyoto Prefectural University of Medicine7, Shiga University of Medical Science8, Kindai University9, Saga University10, University of Tokushima11, University of Shizuoka12, Hiroshima University13, Nagoya University14, Osaka University15, Tohoku University16, Kwansei Gakuin University17
TL;DR: A large-scale genome-wide association study of 168,228 individuals of Japanese ancestry with genotype imputation with genotypes imputation detected eight new susceptibility loci and Japanese-specific rare variants contributing to disease severity and increased cardiovascular mortality, and a trans-ancestry meta-analysis found 35 additional new loci.
Abstract: To elucidate the genetics of coronary artery disease (CAD) in the Japanese population, we conducted a large-scale genome-wide association study of 168,228 individuals of Japanese ancestry (25,892 cases and 142,336 controls) with genotype imputation using a newly developed reference panel of Japanese haplotypes including 1,781 CAD cases and 2,636 controls. We detected eight new susceptibility loci and Japanese-specific rare variants contributing to disease severity and increased cardiovascular mortality. We then conducted a trans-ancestry meta-analysis and discovered 35 additional new loci. Using the meta-analysis results, we derived a polygenic risk score (PRS) for CAD, which outperformed those derived from either Japanese or European genome-wide association studies. The PRS prioritized risk factors among various clinical parameters and segregated individuals with increased risk of long-term cardiovascular mortality. Our data improve the clinical characterization of CAD genetics and suggest the utility of trans-ancestry meta-analysis for PRS derivation in non-European populations.
Hokkaido University1, University of Tsukuba2, Kyorin University3, Kindai University4, Kyushu University5, St. Marianna University School of Medicine6, Osaka University7, Japanese Foundation for Cancer Research8, Osaka Medical College9, Gifu University10, Kanazawa University11, Kagawa University12, Hiroshima University13
TL;DR: An observational study on a large cohort of patients with gastrointestinal cancer demonstrates the utility of ctDNA analysis for accelerating the enrollment of patients in clinical trials with no accompanying deterioration in treatment efficacy.
Abstract: Comprehensive genomic profiling enables genomic biomarker detection in advanced solid tumors. Here, to evaluate the utility of circulating tumor DNA (ctDNA) genotyping, we compare trial enrollment using ctDNA sequencing in 1,687 patients with advanced gastrointestinal (GI) cancer in SCRUM-Japan GOZILA (no. UMIN000016343), an observational ctDNA-based screening study, to enrollment using tumor tissue sequencing in the same centers and network (GI-SCREEN, 5,621 patients). ctDNA genotyping significantly shortened the screening duration (11 versus 33 days, P < 0.0001) and improved the trial enrollment rate (9.5 versus 4.1%, P < 0.0001) without compromising treatment efficacy compared to tissue genotyping. We also describe the clonal architecture of ctDNA profiles in ~2,000 patients with advanced GI cancer, which reinforces the relevance of many targetable oncogenic drivers and highlights multiple new drivers as candidates for clinical development. ctDNA genotyping has the potential to accelerate innovation in precision medicine and its delivery to individual patients. An observational study on a large cohort of patients with gastrointestinal cancer demonstrates the utility of ctDNA analysis for accelerating the enrollment of patients in clinical trials with no accompanying deterioration in treatment efficacy.
University of Tokyo1, University of Tsukuba2, Osaka University3, Hokkaido University4, Kanazawa Medical University5, Nagoya University6, Hiroshima University7, Yamaguchi University8, Saitama Medical University9, Hamamatsu University School of Medicine10, Showa University11, University of Toyama12, Kyoto University13, University of Tokushima14, Kyushu University15, National University of Ireland, Galway16, University of Southern California17, University of California, Irvine18, Georgia State University19
TL;DR: It is found that schizophrenia, bipolar disorder, and autism spectrum disorder share similar white matter microstructural differences in the body of the corpus callosum; schizophrenia and bipolar disorder featured comparable changes in the limbic system, such as the fornix and cingulum.
Abstract: Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophrenia; however, no similar cross-disorder study has been carried out to date. Here, we conducted mega-analyses comparing white matter microstructural differences between healthy comparison subjects (HCS; N = 1506) and patients with schizophrenia (N = 696), bipolar disorder (N = 211), autism spectrum disorder (N = 126), or major depressive disorder (N = 398; total N = 2937 from 12 sites). In comparison with HCS, we found that schizophrenia, bipolar disorder, and autism spectrum disorder share similar white matter microstructural differences in the body of the corpus callosum; schizophrenia and bipolar disorder featured comparable changes in the limbic system, such as the fornix and cingulum. By comparison, alterations in tracts connecting neocortical areas, such as the uncinate fasciculus, were observed only in schizophrenia. No significant difference was found in major depressive disorder. In a direct comparison between schizophrenia and bipolar disorder, there were no significant differences. Significant differences between schizophrenia/bipolar disorder and major depressive disorder were found in the limbic system, which were similar to the differences in schizophrenia and bipolar disorder relative to HCS. While schizophrenia and bipolar disorder may have similar pathological characteristics, the biological characteristics of major depressive disorder may be close to those of HCS. Our findings provide insights into nosology and encourage further investigations of shared and unique pathophysiology of psychiatric disorders.
Saint Petersburg State University1, Ikerbasque2, Spanish National Research Council3, Tomsk State University4, Russian Academy of Sciences5, Helmholtz-Zentrum Berlin6, University of the Basque Country7, Donostia International Physics Center8, Johannes Kepler University of Linz9, Azerbaijan National Academy of Sciences10, Baku State University11, Hiroshima University12, Novosibirsk State University13, Elettra Sincrotrone Trieste14, Max Planck Society15
TL;DR: In this paper, a tight-binding band structure calculation was performed in the St. Petersburg State University Computing Center (http://spin.lab.spbu.ru) with the support of the Russian Science Foundation.
Abstract: This work is supported by Saint Petersburg State University project for scientific investigations (ID No. 51126254, https://spin.lab.spbu.ru) and Russian Science Foundation (Grant no. 18-12-00062 in part of the photoemission measurements and 18-12-00169 in part of calculations of topological invariants, investigation of dependence of the electronic spectra on SOC strength, and tight-binding band structure calculations). Russian Foundation for Basic Research (Grant nos. 20-32-70179 and 18-52-06009) and Science Development Foundation under the President of the Republic of Azerbaijan (Grant no. EIF-BGM-4-RFTF-1/2017-21/04/1-M-02) are acknowledged. We also acknowledge the support by the Basque Departamento de Educacion, UPV/EHU (Grant no. IT-756-13), Spanish Ministerio de Ciencia e Innovacion (Grant no. PID2019-103910GB-I00), the Fundamental Research Program of the State Academies of Sciences (line of research III.23.2.9) and Tomsk State University competitiveness improvement program (project no. 8.1.01.2018). I.P.R. acknowledge support from Ministry of Education and Science of the Russian Federation (State Task No. 0721-2020-0033) (tight-binding calculations). The calculations were performed in Donostia International Physics Center and in the Research park of St. Petersburg State University Computing Center (http://cc.spbu.ru).
TL;DR: On DLR images, the image noise was lower, and high-contrast spatial resolution and task-based detectability were better than on images reconstructed with other state-of-the art techniques.
TL;DR: This finding illustrates the vital roles of circRNF20 via the circR NF20/ miR-487a/HIF-1α/HK2 axis in breast cancer progress and Warburg effect, providing an interesting insight for the BC tumorigenesis.
Abstract: Compelling evidence has demonstrated the potential functions of circular RNAs (circRNAs) in breast cancer (BC) tumorigenesis. Nevertheless, the underlying mechanism by which circRNAs regulate BC progression is still unclear. The purpose of present research was to investigate the novel circRNA circRNF20 (hsa_circ_0087784) and its role in BC. CircRNA microarray sequencing revealed that circRNF20 was one of the upregulated transcripts in BC samples. Increased circRNF20 level predicted the poor clinical outcome in BC specimens. Functionally, circRNF20 promoted the proliferation and Warburg effect (aerobic glycolysis) of BC cells. Mechanistically, circRNF20 harbor miR-487a, acting as miRNA sponge, and then miR-487a targeted the 3’-UTR of hypoxia-inducible factor-1α (HIF-1α). Moreover, HIF-1α could bind with the promoter of hexokinase II (HK2) and promoted its transcription. In conclusion, this finding illustrates the vital roles of circRNF20 via the circRNF20/ miR-487a/HIF-1α/HK2 axis in breast cancer progress and Warburg effect, providing an interesting insight for the BC tumorigenesis.
TL;DR: The safety and efficacy profile from this study supports the role of dupilumab as continuous long-term treatment for patients with moderate-to-severe atopic dermatitis.
Abstract: Background Significant unmet need exists for long-term treatment of moderate to severe atopic dermatitis (AD). Objective To assess the long-term safety and efficacy of dupilumab in patients with AD. Methods This ongoing, multicenter, open-label extension study (NCT01949311) evaluated long-term dupilumab treatment in adults who had previously participated in phase 1 through 3 clinical trials of dupilumab for AD. This analysis examined patients given 300 mg dupilumab weekly for up to 76 weeks at data cutoff (April 2016). Safety was the primary outcome; efficacy was also evaluated. Results Of 1491 enrolled patients (1042.9 patient-years), 92.9% were receiving treatment at cutoff. The safety profile was consistent with previously reported trials (420.4 adverse events/100 patient-years and 8.5 serious adverse events/100 patient-years), with no new safety signals; common adverse events included nasopharyngitis, conjunctivitis, and injection-site reactions. Sustained improvement was seen up to 76 weeks in all efficacy outcomes, including measures of skin inflammation, pruritus, and quality of life. Limitations Lack of control arm, limited number of patients with 76 weeks or longer of treatment (median follow-up, 24 weeks), and patients not receiving the approved dose regimen of 300 mg every 2 weeks. Conclusion The safety and efficacy profile from this study supports the role of dupilumab as continuous long-term treatment for patients with moderate to severe AD.
TL;DR: This typology study can serve as a frame of reference for those aiming at evaluating performance of smart cities using appropriate schemes, can be used as a basis for conducting further critical analyses of assessment schemes, and may also guide the development of better-informed schemes in the future.
Nagoya University1, University of Tokyo2, Chiba Institute of Technology3, Osaka University4, University of La Laguna5, Spanish National Research Council6, Japan Aerospace Exploration Agency7, Kōchi University8, Kobe University9, Rikkyo University10, University of Aizu11, National Institute of Advanced Industrial Science and Technology12, Meiji University13, Auburn University14, Planetary Science Institute15, Kindai University16, Brown University17, Johns Hopkins University Applied Physics Laboratory18, Tohoku University19, Centre national de la recherche scientifique20, University of Paris-Sud21, Graduate University for Advanced Studies22, Tokyo City University23, Hiroshima University24, National Institute for Environmental Studies25, University of Liverpool26
TL;DR: The authors conclude that the asteroid experienced a prior period of strong solar heating caused by changes in its orbit, and suggest that Ryugu previously experienced an orbital excursion near the Sun.
Abstract: The near-Earth asteroid (162173) Ryugu is thought to be a primitive carbonaceous object that contains hydrated minerals and organic molecules. We report sample collection from Ryugu's surface by the Hayabusa2 spacecraft on 21 February 2019. Touchdown images and global observations of surface colors are used to investigate the stratigraphy of the surface around the sample location and across Ryugu. Latitudinal color variations suggest the reddening of exposed surface material by solar heating and/or space weathering. Immediately after touchdown, Hayabusa2's thrusters disturbed dark, fine grains that originate from the redder materials. The stratigraphic relationship between identified craters and the redder material indicates that surface reddening occurred over a short period of time. We suggest that Ryugu previously experienced an orbital excursion near the Sun.
TL;DR: In this paper, the authors conducted scenario simulations to depict the role of transport electrification in climate changemitigation and how the transport sector would interact with the energy-supply sector.
Abstract: Electrification is widely considered an attractive solution for reducing the oil dependency and environmental impact of road transportation.Many countries have been establishing increasingly stringent and ambitious targets in support of transport electrification.We conducted scenario simulations to depict the role of transport electrification in climate changemitigation and how the transport sector would interact with the energy-supply sector. The results showed that transport electrificationwithout the replacement of fossil-fuel power plants leads to the unfortunate result of increasing emissions instead of achieving a low-carbon transition.While transport electrification alonewould not contribute to climate changemitigation, it is interesting to note that switching to electrified road transport under the sustainable shared socioeconomic pathways permitted an optimistic outlook for a low-carbon transition, even in the absence of a decarbonized power sector. Another interesting findingwas that the stringent penetration of electric vehicles can reduce the mitigation cost generated by the 2 °C climate stabilization target, implying a positive impact for transport policies on the economic system.With technological innovations such as electrified road transport, climate changemitigation does not have to occur at the expense of economic growth. Because a transport electrification policy closely interacts with energy and economic systems, transport planners, economists, and energy policymakers need towork together to propose policy schemes that consider a cross-sectoral balance for a green sustainable future.