Showing papers by "Yonsei University published in 2020"
TL;DR: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates, and there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries.
5,802 citations
Christopher J L Murray1, Christopher J L Murray2, Christopher J L Murray3, Aleksandr Y. Aravkin1 +2269 more•Institutions (286)
TL;DR: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure.
3,059 citations
University of Sydney1, University Hospitals Birmingham NHS Foundation Trust2, Newcastle upon Tyne Hospitals NHS Foundation Trust3, Spanish National Research Council4, University of Haifa5, The Chinese University of Hong Kong6, University of Bern7, University of Mainz8, Kurume University9, Pontifical Catholic University of Chile10, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico11, Mansoura University12, Minerva Foundation Institute for Medical Research13, Shanghai Jiao Tong University14, Aarhus University Hospital15, Marmara University16, University of Lisbon17, University of São Paulo18, Paris Diderot University19, University of Western Australia20, First Affiliated Hospital of Wenzhou Medical University21, Minia University22, University of Malaya23, National Autonomous University of Mexico24, Yonsei University25, University of Paris26, University of Turin27
TL;DR: A panel of international experts from 22 countries propose a new definition of metabolic-dysfunction-associated fatty liver disease that is both comprehensive yet simple for the diagnosis of MAFLD and is independent of other liver diseases.
1,705 citations
French Institute of Health and Medical Research1, Johns Hopkins University2, Tel Aviv Sourasky Medical Center3, University of Texas MD Anderson Cancer Center4, Yonsei University5, New Generation University College6, Sheba Medical Center7, Ohio State University8, Merck & Co.9, Memorial Sloan Kettering Cancer Center10
TL;DR: The study demonstrates the clinical benefit of anti-programmed death-1 therapy with pembrolizumab among patients with previously treated unresectable or metastatic MSI-H/dMMR noncolorectal cancer.
Abstract: PURPOSEGenomes of tumors that are deficient in DNA mismatch repair (dMMR) have high microsatellite instability (MSI-H) and harbor hundreds to thousands of somatic mutations that encode potential ne...
1,478 citations
Emory University1, Katholieke Universiteit Leuven2, Institut Gustave Roussy3, Yonsei University4, Mahidol University5, Chiang Mai University6, Maidstone Hospital7, Chungbuk National University8, University of Toronto9, University of Parma10, Chang Gung University11, Kansai Medical University12, AstraZeneca13, Université Paris-Saclay14
TL;DR: Among patients with previously untreated advanced NSCLC with an EGFR mutation, those who received osimertinib had longer overall survival than those whoreceived a comparator EGFR-TKI.
Abstract: Background Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI–sensitizing ...
1,395 citations
TL;DR: ShinyGO is an intuitive, graphical web application that can help researchers gain actionable insights from gene lists, based on a large annotation database derived from Ensembl and STRING-db for 59 plant, 256 animal, 115 archaeal, and 1678 bacterial species.
Abstract: MotivationGene lists are routinely produced from various omic studies. Enrichment analysis can link these gene lists with underlying molecular pathways and functional categories such as gene ontology (GO) and other databases. ResultsTo complement existing tools, we developed ShinyGO based on a large annotation database derived from Ensembl and STRING-db for 59 plant, 256 animal, 115 archeal and 1678 bacterial species. ShinyGO’s novel features include graphical visualization of enrichment results and gene characteristics, and application program interface access to KEGG and STRING for the retrieval of pathway diagrams and protein–protein interaction networks. ShinyGO is an intuitive, graphical web application that can help researchers gain actionable insights from gene-sets. Availability and implementationhttp://ge-lab.org/go/. Supplementary informationSupplementary data are available at Bioinformatics online.
1,174 citations
Université Paris-Saclay1, City of Hope National Medical Center2, Institute of Cancer Research3, Ohio State University4, Sheba Medical Center5, Kindai University6, Yonsei University7, University of Chicago8, McGill University9, University of Bordeaux10, University of Texas MD Anderson Cancer Center11, Mayo Clinic12, Foundation Medicine13, Merck & Co.14, New Generation University College15
TL;DR: The association of high tissue TMB (tTMB-high) with outcomes in ten tumour-type-specific cohorts from the phase 2 KEYNOTE-158 study, which assessed the anti-PD-1 monoclonal antibody pembrolizumab in patients with selected, previously treated, advanced solid tumours, was prospectively explored.
Abstract: Summary Background Tumour mutational burden (TMB) has been retrospectively correlated with response to immune checkpoint blockade. We prospectively explored the association of high tissue TMB (tTMB-high) with outcomes in ten tumour-type-specific cohorts from the phase 2 KEYNOTE-158 study, which assessed the anti-PD-1 monoclonal antibody pembrolizumab in patients with selected, previously treated, advanced solid tumours. Methods In the multi-cohort, open-label, non-randomised, phase 2 KEYNOTE-158 study, patients were enrolled from 81 academic facilities and community-based institutions across 21 countries in Africa, the Americas, Asia, and Europe. Eligible patients were aged 18 years or older, had a histologically or cytologically confirmed advanced (ie, unresectable or metastatic, or both) incurable solid tumour (eligible tumour types were anal, biliary, cervical, endometrial, mesothelioma, neuroendocrine, salivary, small-cell lung, thyroid, and vulvar), progression on or intolerance to one or more lines of standard therapy, had measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) assessed by independent central radiological review, Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, adequate organ function, and a tumour sample for biomarker analysis. Participants were given pembrolizumab 200 mg intravenously every 3 weeks for up to 35 cycles. Tissue TMB (tTMB) was assessed in formalin-fixed paraffin-embedded tumour samples using the FoundationOne CDx assay (Foundation Medicine, Cambridge, MA, USA). The prespecified definition of tTMB-high status was at least 10 mutations per megabase. The primary endpoint was the proportion of patients with an objective response (complete or partial response) as per Response Evaluation Criteria in Solid Tumours (version 1.1) by independent central review. This prespecified analysis assessed the association between antitumour activity and tTMB in treated patients with evaluable tTMB data. Efficacy was assessed in all participants who received at least one dose of pembrolizumab, had evaluable tTMB data, and were enrolled at least 26 weeks before data cutoff (June 27, 2019), and safety was assessed in all participants who received at least one dose of pembrolizumab and had tTMB-high status. KEYNOTE-158 is registered at ClinicalTrials.gov, NCT02628067, and is ongoing. Findings Between Jan 15, 2016, and June 25, 2019, 1073 patients were enrolled. 1066 participants were treated as of data cutoff (June 27, 2019), of whom 805 (76%) were evaluable for TMB, and 105 (13%) of 805 had tTMB-high status and were assessed for safety. 1050 (98%) of 1066 patients enrolled by at least 26 weeks before data cutoff, of whom 790 (75%) were evaluable for TMB and included in efficacy analyses. 102 (13%) of these 790 patients had tTMB-high status (≥10 mutations per megabase), and 688 (87%) patients had non-tTMB-high status ( Interpretation tTMB-high status identifies a subgroup of patients who could have a robust tumour response to pembrolizumab monotherapy. tTMB could be a novel and useful predictive biomarker for response to pembrolizumab monotherapy in patients with previously treated recurrent or metastatic advanced solid tumours. Funding Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.
1,124 citations
Memorial Sloan Kettering Cancer Center1, University of Ulsan2, Institut Gustave Roussy3, Japanese Foundation for Cancer Research4, Kindai University5, Showa University6, Yonsei University7, National Cancer Research Institute8, University of California, Los Angeles9, Daiichi Sankyo10, Harvard University11
TL;DR: Tastuzumab deruxtecan showed durable antitumor activity in a pretreated patient population with HER2-positive metastatic breast cancer and requires attention to pulmonary symptoms and careful monitoring.
Abstract: Background Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linke...
961 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
University of Colorado Boulder1, Memorial Sloan Kettering Cancer Center2, Cornell University3, Complutense University of Madrid4, University of Milan5, Harvard University6, University of California, San Francisco7, Yonsei University8, Institut Gustave Roussy9, University of California, San Diego10, University of Michigan11, Northwestern University12, Huntsman Cancer Institute13, Georgetown University14, City of Hope National Medical Center15, University of Texas MD Anderson Cancer Center16, The Chinese University of Hong Kong17, University of Alcalá18, University of Southern California19, Emory University20, University of Göttingen21, Children's Hospital of Philadelphia22, Genentech23
TL;DR: Results show that entrectinib induced durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumours, and was well tolerated with a manageable safety profile.
Abstract: Summary Background Entrectinib is a potent inhibitor of tropomyosin receptor kinase (TRK) A, B, and C, which has been shown to have anti-tumour activity against NTRK gene fusion-positive solid tumours, including CNS activity due to its ability to penetrate the blood–brain barrier. We present an integrated efficacy and safety analysis of patients with metastatic or locally advanced solid tumours harbouring oncogenic NTRK1, NTRK2, and NTRK3 gene fusions treated in three ongoing, early-phase trials. Methods An integrated database comprised the pivotal datasets of three, ongoing phase 1 or 2 clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2), which enrolled patients aged 18 years or older with metastatic or locally advanced NTRK fusion-positive solid tumours who received entrectinib orally at a dose of at least 600 mg once per day in a capsule. All patients had an Eastern Cooperative Oncology Group performance status of 0–2 and could have received previous anti-cancer therapy (except previous TRK inhibitors). The primary endpoints, the proportion of patients with an objective response and median duration of response, were evaluated by blinded independent central review in the efficacy-evaluable population (ie, patients with NTRK fusion-positive solid tumours who were TRK inhibitor-naive and had received at least one dose of entrectinib). Overall safety evaluable population included patients from STARTRK-1, STARTRK-2, ALKA-372-001, and STARTRK-NG ( NCT02650401 ; treating young adult and paediatric patients [aged ≤21 years]), who received at least one dose of entrectinib, regardless of tumour type or gene rearrangement. NTRK fusion-positive safety evaluable population comprised all patients who have received at least one dose of entrectinib regardless of dose or follow-up. These ongoing studies are registered with ClinicalTrials.gov , NCT02097810 (STARTRK-1) and NCT02568267 (STARTRK-2), and EudraCT, 2012–000148–88 (ALKA-372-001). Findings Patients were enrolled in ALKA-372–001 from Oct 26, 2012, to March 27, 2018; in STARTRK-1 from Aug 7, 2014, to May 10, 2018; and in STARTRK-2 from Nov 19, 2015 (enrolment is ongoing). At the data cutoff date for this analysis (May 31, 2018) the efficacy-evaluable population comprised 54 adults with advanced or metastatic NTRK fusion-positive solid tumours comprising ten different tumour types and 19 different histologies. Median follow-up was 12.9 months (IQR 8·77–18·76). 31 (57%; 95% CI 43·2–70·8) of 54 patients had an objective response, of which four (7%) were complete responses and 27 (50%) partial reponses. Median duration of response was 10 months (95% CI 7·1 to not estimable). The most common grade 3 or 4 treatment-related adverse events in both safety populations were increased weight (seven [10%] of 68 patients in the NTRK fusion-positive safety population and in 18 [5%] of 355 patients in the overall safety-evaluable population) and anaemia (8 [12%] and 16 [5%]). The most common serious treatment-related adverse events were nervous system disorders (three [4%] of 68 patients and ten [3%] of 355 patients). No treatment-related deaths occurred. Interpretation Entrectinib induced durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumours, and was well tolerated with a manageable safety profile. These results show that entrectinib is a safe and active treatment option for patients with NTRK fusion-positive solid tumours. These data highlight the need to routinely test for NTRK fusions to broaden the therapeutic options available for patients with NTRK fusion-positive solid tumours. Funding Ignyta/F Hoffmann-La Roche.
871 citations
Helmholtz-Zentrum Berlin1, Ben-Gurion University of the Negev2, National Renewable Energy Laboratory3, University of Erlangen-Nuremberg4, Forschungszentrum Jülich5, University of Rome Tor Vergata6, Massachusetts Institute of Technology7, Princeton University8, Chulalongkorn University9, Wuhan University of Technology10, Karlsruhe Institute of Technology11, University of Grenoble12, Commonwealth Scientific and Industrial Research Organisation13, University of Michigan14, Sapienza University of Rome15, École Polytechnique Fédérale de Lausanne16, VU University Amsterdam17, University of Jena18, Bangor University19, University of California, Davis20, University of Maryland, College Park21, Shaanxi Normal University22, Dalian Institute of Chemical Physics23, Chinese Academy of Sciences24, University of Southern Denmark25, University of Colorado Boulder26, State University of Campinas27, Boğaziçi University28, Sungkyunkwan University29, Swansea University30, Technische Universität Darmstadt31, University of Oxford32, University of Cambridge33, Skolkovo Institute of Science and Technology34, Imperial College London35, Yonsei University36
TL;DR: A consensus between researchers in the field is reported on procedures for testing perovskite solar cell stability, which are based on the International Summit on Organic Photovoltaic Stability (ISOS) protocols, and additional procedures to account for properties specific to PSCs are proposed.
Abstract: Improving the long-term stability of perovskite solar cells is critical to the deployment of this technology. Despite the great emphasis laid on stability-related investigations, publications lack consistency in experimental procedures and parameters reported. It is therefore challenging to reproduce and compare results and thereby develop a deep understanding of degradation mechanisms. Here, we report a consensus between researchers in the field on procedures for testing perovskite solar cell stability, which are based on the International Summit on Organic Photovoltaic Stability (ISOS) protocols. We propose additional procedures to account for properties specific to PSCs such as ion redistribution under electric fields, reversible degradation and to distinguish ambient-induced degradation from other stress factors. These protocols are not intended as a replacement of the existing qualification standards, but rather they aim to unify the stability assessment and to understand failure modes. Finally, we identify key procedural information which we suggest reporting in publications to improve reproducibility and enable large data set analysis. Reliability of stability data for perovskite solar cells is undermined by a lack of consistency in the test conditions and reporting. This Consensus Statement outlines practices for testing and reporting stability tailoring ISOS protocols for perovskite devices.
TL;DR: It is proposed that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.
Abstract: Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1β-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1β-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.
Cornell University1, Tokyo Institute of Technology2, Yonsei University3, Uppsala University4, Linköping University5, National Institutes of Health6, Memorial Sloan Kettering Cancer Center7, University of Porto8, Rockefeller University9, École Polytechnique Fédérale de Lausanne10, Carlos III Health Institute11, University of Tokyo12, Ohio State University13, Princeton University14, University of Oviedo15, Icahn School of Medicine at Mount Sinai16, Weizmann Institute of Science17, Lucile Packard Children's Hospital18, New York University19, Champalimaud Foundation20, University of Nebraska Medical Center21, Fred Hutchinson Cancer Research Center22, University of Pennsylvania23, University of California, San Diego24, University of Vermont25, University of Southern California26, City of Hope National Medical Center27, Lawrence Berkeley National Laboratory28
TL;DR: EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type, and a panel of tumor-type-specific EVP proteins in TEs and plasma are defined, which can classify tumors of unknown primary origin.
TL;DR: In this paper, the authors proposed a new type of high-gain yet low-cost RIS that bears 256 elements, where positive intrinsic negative (PIN) diodes are used to realize 2-bit phase shifting for beamforming.
Abstract: One of the key enablers of future wireless communications is constituted by massive multiple-input multiple-output (MIMO) systems, which can improve the spectral efficiency by orders of magnitude. In existing massive MIMO systems, however, conventional phased arrays are used for beamforming. This method results in excessive power consumption and high hardware costs. Recently, reconfigurable intelligent surface (RIS) has been considered as one of the revolutionary technologies to enable energy-efficient and smart wireless communications, which is a two-dimensional structure with a large number of passive elements. In this paper, we develop a new type of high-gain yet low-cost RIS that bears 256 elements. The proposed RIS combines the functions of phase shift and radiation together on an electromagnetic surface, where positive intrinsic-negative (PIN) diodes are used to realize 2-bit phase shifting for beamforming. This radical design forms the basis for the world's first wireless communication prototype using RIS having 256 two-bit elements. The prototype consists of modular hardware and flexible software that encompass the following: the hosts for parameter setting and data exchange, the universal software radio peripherals (USRPs) for baseband and radio frequency (RF) signal processing, as well as the RIS for signal transmission and reception. Our performance evaluation confirms the feasibility and efficiency of RISs in wireless communications. We show that, at 2.3 GHz, the proposed RIS can achieve a 21.7 dBi antenna gain. At the millimeter wave (mmWave) frequency, that is, 28.5 GHz, it attains a 19.1 dBi antenna gain. Furthermore, it has been shown that the RIS-based wireless communication prototype developed is capable of significantly reducing the power consumption.
TL;DR: In this review, recent advances made in the development and biological applications of synthetic ratiometric fluorescent probes are described and particular emphasis is given to organic dye-based ratiomet fluorescent probes that are designed to detect biologically important and relevant ions in cells and living organisms.
Abstract: Metal cations and anions are essential for versatile physiological processes. Dysregulation of specific ion levels in living organisms is known to have an adverse effect on normal biological events. Owing to the pathophysiological significance of ions, sensitive and selective methods to detect these species in biological systems are in high demand. Because they can be used in methods for precise and quantitative analysis of ions, organic dye-based ratiometric fluorescent probes have been extensively explored in recent years. In this review, recent advances (2015-2019) made in the development and biological applications of synthetic ratiometric fluorescent probes are described. Particular emphasis is given to organic dye-based ratiometric fluorescent probes that are designed to detect biologically important and relevant ions in cells and living organisms. Also, the fundamental principles associated with the design of ratiometric fluorescent probes and perspectives about how to expand their biological applications are discussed.
Stanford University1, Kyoto University2, Universitaire Ziekenhuizen Leuven3, Yonsei University4, French Institute of Health and Medical Research5, University of Vermont6, Kaiser Permanente7, University of Tübingen8, University of Padua9, Eli Lilly and Company10, The Royal Marsden NHS Foundation Trust11
TL;DR: The addition of abemaciclib to fulvestrant provided a clinically meaningful median OS benefit of 9.4 months for patients with HR-positive, ERBB2-negative advanced breast cancer that had progressed on endocrine therapy.
Abstract: Importance Statistically significant overall survival (OS) benefits of CDK4 and CDK6 inhibitors in combination with fulvestrant for hormone receptor (HR)–positive, ERBB2 (formerly HER2)-negative advanced breast cancer (ABC) in patients regardless of menopausal status after prior endocrine therapy (ET) has not yet been demonstrated. Objective To compare the effect of abemaciclib plus fulvestrant vs placebo plus fulvestrant on OS at the prespecified interim of MONARCH 2 (338 events) in patients with HR-positive, ERBB2-negative advanced breast cancer that progressed during prior ET. Design, Setting, and Participants MONARCH 2 was a global, randomized, placebo-controlled, double-blind phase 3 trial of abemaciclib plus fulvestrant vs placebo plus fulvestrant for treatment of premenopausal or perimenopausal women (with ovarian suppression) and postmenopausal women with HR-positive, ERBB2-negative ABC that progressed during ET. Patients were enrolled between August 7, 2014, and December 29, 2015. Analyses for this report were conducted at the time of database lock on June 20, 2019. Interventions Patients were randomized 2:1 to receive abemaciclib or placebo, 150 mg, every 12 hours on a continuous schedule plus fulvestrant, 500 mg, per label. Randomization was stratified based on site of metastasis (visceral, bone only, or other) and resistance to prior ET (primary vs secondary). Main Outcomes and Measures The primary end point was investigator-assessed progression-free survival. Overall survival was a gated key secondary end point. The boundaryPvalue for the interim analysis was .02. Results Of 669 women enrolled, 446 (median [range] age, 59 [32-91] years) were randomized to the abemaciclib plus fulvestrant arm and 223 (median [range] age, 62 [32-87] years) were randomized to the placebo plus fulvestrant arm. At the prespecified interim, 338 deaths (77% of the planned 441 at the final analysis) were observed in the intent-to-treat population, with a median OS of 46.7 months for abemaciclib plus fulvestrant and 37.3 months for placebo plus fulvestrant (hazard ratio [HR], 0.757; 95% CI, 0.606-0.945;P = .01). Improvement in OS was consistent across all stratification factors. Among stratification factors, more pronounced effects were observed in patients with visceral disease (HR, 0.675; 95% CI, 0.511-0.891) and primary resistance to prior ET (HR, 0.686; 95% CI, 0.451-1.043). Time to second disease progression (median, 23.1 months vs 20.6 months), time to chemotherapy (median, 50.2 months vs 22.1 months), and chemotherapy-free survival (median, 25.5 months vs 18.2 months) were also statistically significantly improved in the abemaciclib arm vs placebo arm. No new safety signals were observed for abemaciclib. Conclusions and Relevance Treatment with abemaciclib plus fulvestrant resulted in a statistically significant and clinically meaningful median OS improvement of 9.4 months for patients with HR-positive, ERBB2-negative ABC who progressed after prior ET regardless of menopausal status. Abemaciclib substantially delayed the receipt of subsequent chemotherapy. Trial Registration ClinicalTrials.gov identifier:NCT02107703
Katholieke Universiteit Leuven1, New Generation University College2, Yale Cancer Center3, Seoul National University Bundang Hospital4, Pontifical Catholic University of Chile5, Yonsei University6, Samsung Medical Center7, Universidad del Desarrollo8, University of Chile9, Harvard University10, Northwestern University11, City of Hope National Medical Center12, University of California, San Francisco13, University of California, Los Angeles14, Merck & Co.15, Hebron University16
TL;DR: This phase 3 randomized clinical trial found that among patients with untreated, advanced G/GEJ cancer, pembrolizumab was noninferior to chemotherapy, with fewer adverse events observed.
Abstract: Importance Safe and effective therapies for untreated, advanced gastric/gastroesophageal junction (G/GEJ) cancer remain an unmet need. Objective To evaluate the antitumor activity of pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy alone in patients with untreated, advanced G/GEJ cancer with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or greater. Design, Setting, and Participants The phase 3 KEYNOTE-062 randomized, controlled, partially blinded interventional trial enrolled 763 patients with untreated, locally advanced/unresectable or metastatic G/GEJ cancer with PD-L1 CPS of 1 or greater from 200 centers in 29 countries between September 18, 2015, and May 26, 2017. Interventions Patients were randomized 1:1:1 to pembrolizumab 200 mg, pembrolizumab plus chemotherapy (cisplatin 80 mg/m2/d on day 1 plus fluorouracil 800 mg/m2/d on days 1 to 5 or capecitabine 1000 mg/m2twice daily), or chemotherapy plus placebo, every 3 weeks. Main Outcomes and Measures Primary end points were overall survival (OS) and progression-free survival (PFS) in patients with PD-L1 CPS of 1 or greater or 10 or greater. Results A total of 763 patients were randomized to pembrolizumab (n = 256), pembrolizumab plus chemotherapy (n = 257), or chemotherapy (n = 250). The median (range) age of all patients in the study cohort was 62 (20-87) years; 554 of 763 (72.6%) were men. At final analysis, after a median (range) follow-up of 29.4 (22.0-41.3) months, pembrolizumab was noninferior to chemotherapy for OS in patients with CPS of 1 or greater (median, 10.6 vs 11.1 months; hazard ratio [HR], 0.91; 99.2% CI, 0.69-1.18). Pembrolizumab monotherapy was not superior to chemotherapy in patients with CPS of 1 or greater. Pembrolizumab prolonged OS vs chemotherapy in patients with CPS of 10 or greater (median, 17.4 vs 10.8 months; HR, 0.69; 95% CI, 0.49-0.97), but this difference was not statistically tested. Pembrolizumab plus chemotherapy was not superior to chemotherapy for OS in patients with CPS of 1 or greater (12.5 vs 11.1 months; HR, 0.85; 95% CI, 0.70-1.03;P = .05) or CPS of 10 or greater (12.3 vs 10.8 months; HR, 0.85; 95% CI, 0.62-1.17;P = .16) or for PFS in patients with CPS of 1 or greater (6.9 vs 6.4 months; HR, 0.84; 95% CI, 0.70-1.02;P = .04). Grade 3 to 5 treatment-related adverse event rates for pembrolizumab, pembrolizumab plus chemotherapy, and chemotherapy were 17%, 73%, and 69%, respectively. Conclusions and Relevance This phase 3 randomized clinical trial found that among patients with untreated, advanced G/GEJ cancer, pembrolizumab was noninferior to chemotherapy, with fewer adverse events observed. Pembrolizumab or pembrolizumab plus chemotherapy was not superior to chemotherapy for the OS and PFS end points tested. Trial Registration ClinicalTrials.gov Identifier:NCT02494583
TL;DR: A systematic review of Web of Science/grey literature until 15th April 2020, to identify studies reporting physical/mental health outcomes in HCW infected/exposed to Severe Acute Respiratory Syndrome -SARS, Middle East Respiratories Syndrome -MERS, Novel coronavirus -COVID-19.
Cornell University1, Harvard University2, The Chinese University of Hong Kong3, Sarah Cannon Research Institute4, University of California, San Francisco5, University of Bern6, Institut Gustave Roussy7, Yonsei University8, Ben-Gurion University of the Negev9, University of North Carolina at Chapel Hill10, Seoul National University11, Japanese Foundation for Cancer Research12, Sungkyunkwan University13, University of Chicago14, Tottori University15, Ohio State University16, University of California, San Diego17, New York University18, Okayama University19, University of Milan20, City of Hope National Medical Center21, Roswell Park Cancer Institute22, University of Cologne23, Peter MacCallum Cancer Centre24, University of Texas MD Anderson Cancer Center25
TL;DR: Selpercatinib had durable efficacy, including intracranial activity, with mainly low-grade toxic effects in patients with RET fusion-positive NSCLC who had previously received platinum-based chemotherapy and those who were previously untreated.
Abstract: Background RET fusions are oncogenic drivers in 1 to 2% of non–small-cell lung cancers (NSCLCs). In patients with RET fusion–positive NSCLC, the efficacy and safety of selective RET inhibi...
TL;DR: In this article, a blockchained federated learning (BlockFL) architecture is proposed, where local learning model updates are exchanged and verified by utilizing a consensus mechanism in blockchain.
Abstract: By leveraging blockchain, this letter proposes a blockchained federated learning (BlockFL) architecture where local learning model updates are exchanged and verified. This enables on-device machine learning without any centralized training data or coordination by utilizing a consensus mechanism in blockchain. Moreover, we analyze an end-to-end latency model of BlockFL and characterize the optimal block generation rate by considering communication, computation, and consensus delays.
TL;DR: In this paper, the authors used customer data to test a five-dimensional model measuring Chatbot for customer perceptions of interaction, entertainment, trendiness, customization, and problem-solving.
University of Sydney1, The Chinese University of Hong Kong2, Shanghai Jiao Tong University3, Kurume University4, Yonsei University5, Wenzhou Medical College6, Mansoura University7, Marmara University8, University of Indonesia9, Bangabandhu Sheikh Mujib Medical University10, National University of Singapore11, National Taiwan University12, Aga Khan University13, University of Malaya14, Mahidol University15, University of Western Australia16, University of Tokyo17
TL;DR: The clinical practice guidelines of the Asian Pacific Association for the Study of the Liver on MAFLD are presented to improve patient care and awareness of the disease and assist stakeholders in the decision-making process by providing evidence-based data.
Abstract: Metabolic associated fatty liver disease (MAFLD) is the principal worldwide cause of liver disease and affects nearly a quarter of the global population. The objective of this work was to present the clinical practice guidelines of the Asian Pacific Association for the Study of the Liver (APASL) on MAFLD. The guidelines cover various aspects of MAFLD including its epidemiology, diagnosis, screening, assessment, and treatment. The document is intended for practical use and for setting the stage for advancing clinical practice, knowledge, and research of MAFLD in adults, with specific reference to special groups as necessary. The guidelines also seek to improve patient care and awareness of the disease and assist stakeholders in the decision-making process by providing evidence-based data. The guidelines take into consideration the burden of clinical management for the healthcare sector.
Columbia University Medical Center1, Yonsei University2, Chungbuk National University3, Samsung Medical Center4, Netherlands Cancer Institute5, University of Málaga6, Cedars-Sinai Medical Center7, Princess Margaret Cancer Centre8, Prince of Songkla University9, University of California, Los Angeles10, Yale University11, Kindai University12, AstraZeneca13, University Hospital of Lausanne14
TL;DR: Treatment with durvalumab resulted in a numerically reduced risk of death vs chemotherapy in patients with programmed cell death ligand 1 expression on at least 25% of tumor cells, highlighting the need for further investigation and prospective validation of blood tumor mutational burden as a predictive biomarker for immunotherapy.
Abstract: Importance Checkpoint inhibitors targeting programmed cell death 1 or its ligand (PD-L1) as monotherapies or in combination with anti–cytotoxic T-lymphocyte–associated antigen 4 have shown clinical activity in patients with metastatic non–small cell lung cancer. Objective To compare durvalumab, with or without tremelimumab, with chemotherapy as a first-line treatment for patients with metastatic non–small cell lung cancer. Design, Setting, and Participants This open-label, phase 3 randomized clinical trial (MYSTIC) was conducted at 203 cancer treatment centers in 17 countries. Patients with treatment-naive, metastatic non–small cell lung cancer who had no sensitizingEGFRorALKgenetic alterations were randomized to receive treatment with durvalumab, durvalumab plus tremelimumab, or chemotherapy. Data were collected from July 21, 2015, to October 30, 2018. Interventions Patients were randomized (1:1:1) to receive treatment with durvalumab (20 mg/kg every 4 weeks), durvalumab (20 mg/kg every 4 weeks) plus tremelimumab (1 mg/kg every 4 weeks, up to 4 doses), or platinum-based doublet chemotherapy. Main Outcomes and Measures The primary end points, assessed in patients with ≥25% of tumor cells expressing PD-L1, were overall survival (OS) for durvalumab vs chemotherapy, and OS and progression-free survival (PFS) for durvalumab plus tremelimumab vs chemotherapy. Analysis of blood tumor mutational burden (bTMB) was exploratory. Results Between July 21, 2015, and June 8, 2016, 1118 patients were randomized. Baseline demographic and disease characteristics were balanced between treatment groups. Among 488 patients with ≥25% of tumor cells expressing PD-L1, median OS was 16.3 months (95% CI, 12.2-20.8) with durvalumab vs 12.9 months (95% CI, 10.5-15.0) with chemotherapy (hazard ratio [HR], 0.76; 97.54% CI, 0.56-1.02;P = .04 [nonsignificant]). Median OS was 11.9 months (95% CI, 9.0-17.7) with durvalumab plus tremelimumab (HR vs chemotherapy, 0.85; 98.77% CI, 0.61-1.17;P = .20). Median PFS was 3.9 months (95% CI, 2.8-5.0) with durvalumab plus tremelimumab vs 5.4 months (95% CI, 4.6-5.8) with chemotherapy (HR, 1.05; 99.5% CI, 0.72-1.53;P = .71). Among 809 patients with evaluable bTMB, those with a bTMB ≥20 mutations per megabase showed improved OS for durvalumab plus tremelimumab vs chemotherapy (median OS, 21.9 months [95% CI, 11.4-32.8] vs 10.0 months [95% CI, 8.1-11.7]; HR, 0.49; 95% CI, 0.32-0.74). Treatment-related adverse events of grade 3 or higher occurred in 55 (14.9%) of 369 patients who received treatment with durvalumab, 85 (22.9%) of 371 patients who received treatment with durvalumab plus tremelimumab, and 119 (33.8%) of 352 patients who received treatment with chemotherapy. These adverse events led to death in 2 (0.5%), 6 (1.6%), and 3 (0.9%) patients, respectively. Conclusions and Relevance The phase 3 MYSTIC study did not meet its primary end points of improved OS with durvalumab vs chemotherapy or improved OS or PFS with durvalumab plus tremelimumab vs chemotherapy in patients with ≥25% of tumor cells expressing PD-L1. Exploratory analyses identified a bTMB threshold of ≥20 mutations per megabase for optimal OS benefit with durvalumab plus tremelimumab. Trial Registration ClinicalT rials.gov Identifier:NCT02453282
TL;DR: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo, and this trial is registered with ClinicalTrials.gov, NCT02930018.
Memorial Sloan Kettering Cancer Center1, Harvard University2, Hebron University3, Meir Medical Center4, University of Lausanne5, University of Toronto6, University of Las Palmas de Gran Canaria7, National Taiwan University8, Paul Sabatier University9, Istanbul Medeniyet University10, University of Michigan11, Merck & Co.12, Yonsei University13
TL;DR: Pembrolizumab plus EP significantly improved progression-free survival (PFS) and overall survival (OS) compared with placebo plus EP as first-line therapy for patients with ES-SCLC, and these data support the benefit of pembrolIZumab in ES-sCLC.
Abstract: PURPOSEPembrolizumab monotherapy has shown antitumor activity in patients with small-cell lung cancer (SCLC). The randomized, double-blind, phase III KEYNOTE-604 study compared pembrolizumab plus e...
TL;DR: This Review aims to summarize and provide a comprehensive understanding of proton transport in MOFs and discusses the fundamental principles and various design strategies and implementations aimed at enhancing proton conductivity with representative examples.
Abstract: Solid-state proton conductors (SSPCs), which are a key component for the safety and efficiency of fuel cells, have received much attention due to their broad application in electrochemical devices....
TL;DR: To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—the authors estimated additional population equivalents with UHC effective coverage from 2018 to 2023, and quantified frontiers of U HC effective coverage performance on the basis of pooled health spending per capita.
Sarah Cannon Research Institute1, Westmead Hospital2, University of Sydney3, Kansai Medical University4, Chungbuk National University5, Yonsei University6, Institut Gustave Roussy7, Complutense University of Madrid8, University of Manchester9, Katholieke Universiteit Leuven10, AstraZeneca11, Istanbul University12
TL;DR: In the PACIFIC study as mentioned in this paper, patients were randomized to receive durvalumab, 10 mg/kg intravenously every 2 weeks, or placebo for up to 12 months.
TL;DR: To the authors' knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea and both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after theUse of convalscent plasma in addition to systemic corticosteroid.
Abstract: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.
Sungkyunkwan University1, Samsung Medical Center2, Katholieke Universiteit Leuven3, University of Geneva4, Yonsei University5, Korea Research Institute of Bioscience and Biotechnology6, Swiss Institute of Bioinformatics7, Agency for Science, Technology and Research8, National University of Singapore9, New Generation University College10, KAIST11
TL;DR: The collective view of the cellular landscape and intercellular interactions in colorectal cancer provide mechanistic information for the design of efficient immuno-oncology treatment strategies.
Abstract: Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,103 unsorted single cells from 23 Korean and 6 Belgian patients. Cancer cells displayed transcriptional features reminiscent of normal differentiation programs, and genetic alterations that apparently fostered immunosuppressive microenvironments directed by regulatory T cells, myofibroblasts and myeloid cells. Intercellular network reconstruction supported the association between cancer cell signatures and specific stromal or immune cell populations. Our collective view of the cellular landscape and intercellular interactions in colorectal cancer provide mechanistic information for the design of efficient immuno-oncology treatment strategies.