Showing papers by "Yonsei University published in 2017"
TL;DR: Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR sensitizing and T790M resistance mutations in patients with non-small-cell lung cancer as mentioned in this paper.
Abstract: BackgroundOsimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in patients with non–small-cell lung cancer. The efficacy of osimertinib as compared with platinum-based therapy plus pemetrexed in such patients is unknown. MethodsIn this randomized, international, open-label, phase 3 trial, we assigned 419 patients with T790M-positive advanced non–small-cell lung cancer, who had disease progression after first-line EGFR-TKI therapy, in a 2:1 ratio to receive either oral osimertinib (at a dose of 80 mg once daily) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles; maintenance pemetrexed was allowed. In all the patients, disease had progressed during receipt of first-line EGFR-TKI therapy. The primary end point was investigator-assessed pro...
2,337 citations
University of Ulsan1, Osaka University2, Taipei Veterans General Hospital3, University Health System4, Chang Gung University5, Samsung Medical Center6, National Taiwan University7, Korea University8, China Medical University (Taiwan)9, Kindai University10, Seoul National University Bundang Hospital11, Keio University12, Kyungpook National University13, Japanese Foundation for Cancer Research14, Seoul National University Hospital15, Yonsei University16, National Cheng Kung University17, National Health Research Institutes18
TL;DR: In this phase 3 study, the survival benefits indicate that nivolumab might be a new treatment option for heavily pretreated patients with advanced gastric or gastro-oesophageal junction cancer.
1,512 citations
University of Tokyo1, National Taiwan University2, Kindai University3, New Generation University College4, Capital Medical University5, Yonsei University6, Post Graduate Institute of Medical Education and Research7, Juntendo University8, Aga Khan University9, Memorial Hospital of South Bend10, Chiba University11, University of Indonesia12, Teikyo University13, Ankara University14
TL;DR: The latest guidelines for the treatment of HCC recommend evidence-based management and are considered suitable for universal use in the Asia–Pacific region, which has a diversity of medical environments.
Abstract: There is great geographical variation in the distribution of hepatocellular carcinoma (HCC), with the majority of all cases worldwide found in the Asia–Pacific region, where HCC is one of the leading public health problems. Since the “Toward Revision of the Asian Pacific Association for the Study of the Liver (APASL) HCC Guidelines” meeting held at the 25th annual conference of the APASL in Tokyo, the newest guidelines for the treatment of HCC published by the APASL has been discussed. This latest guidelines recommend evidence-based management of HCC and are considered suitable for universal use in the Asia–Pacific region, which has a diversity of medical environments.
1,402 citations
Paris Descartes University1, University College London2, University of Sydney3, Harvard University4, Princess Margaret Cancer Centre5, Sheba Medical Center6, Pomeranian Medical University7, University of New South Wales8, University of Milan9, Saitama Medical University10, Claude Bernard University Lyon 111, The Royal Marsden NHS Foundation Trust12, AstraZeneca13, Institut Gustave Roussy14, Katholieke Universiteit Leuven15, Saint Petersburg State University16, Netherlands Cancer Institute17, Hannover Medical School18, Yonsei University19, Gynecologic Oncology Group20, University of São Paulo21
TL;DR: Olaparib tablet maintenance treatment provided a significant progression-free survival improvement with no detrimental effect on quality of life in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation.
Abstract: Summary Background Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has previously shown efficacy in a phase 2 study when given in capsule formulation to all-comer patients with platinum-sensitive, relapsed high-grade serous ovarian cancer. We aimed to confirm these findings in patients with a BRCA1 or BRCA2 (BRCA1/2 ) mutation using a tablet formulation of olaparib. Methods This international, multicentre, double-blind, randomised, placebo-controlled, phase 3 trial evaluated olaparib tablet maintenance treatment in platinum-sensitive, relapsed ovarian cancer patients with a BRCA1/2 mutation who had received at least two lines of previous chemotherapy. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status at baseline of 0–1 and histologically confirmed, relapsed, high-grade serous ovarian cancer or high-grade endometrioid cancer, including primary peritoneal or fallopian tube cancer. Patients were randomly assigned 2:1 to olaparib (300 mg in two 150 mg tablets, twice daily) or matching placebo tablets using an interactive voice and web response system. Randomisation was stratified by response to previous platinum chemotherapy (complete vs partial) and length of platinum-free interval (6–12 months vs ≥12 months) and treatment assignment was masked for patients, those giving the interventions, data collectors, and data analysers. The primary endpoint was investigator-assessed progression-free survival and we report the primary analysis from this ongoing study. The efficacy analyses were done on the intention-to-treat population; safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01874353, and is ongoing and no longer recruiting patients. Findings Between Sept 3, 2013, and Nov 21, 2014, we enrolled 295 eligible patients who were randomly assigned to receive olaparib (n=196) or placebo (n=99). One patient in the olaparib group was randomised in error and did not receive study treatment. Investigator-assessed median progression-free survival was significantly longer with olaparib (19·1 months [95% CI 16·3–25·7]) than with placebo (5·5 months [5·2–5·8]; hazard ratio [HR] 0·30 [95% CI 0·22–0·41], p vs two [2%] of 99 patients in the placebo group), fatigue or asthenia (eight [4%] vs two [2%]), and neutropenia (ten [5%] vs four [4%]). Serious adverse events were experienced by 35 (18%) patients in the olaparib group and eight (8%) patients in the placebo group. The most common in the olaparib group were anaemia (seven [4%] patients), abdominal pain (three [2%] patients), and intestinal obstruction (three [2%] patients). The most common in the placebo group were constipation (two [2%] patients) and intestinal obstruction (two [2%] patients). One (1%) patient in the olaparib group had a treatment-related adverse event (acute myeloid leukaemia) with an outcome of death. Interpretation Olaparib tablet maintenance treatment provided a significant progression-free survival improvement with no detrimental effect on quality of life in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Apart from anaemia, toxicities with olaparib were low grade and manageable. Funding AstraZeneca.
1,280 citations
University of Alabama at Birmingham1, University of Hohenheim2, College of Health Sciences, Bahrain3, Jimma University4, Queensland Government5, University of Queensland6, Mekelle University7, Institute for Health Metrics and Evaluation8, University of Cartagena9, Komfo Anokye Teaching Hospital10, University of Manitoba11, University of Gondar12, University of São Paulo13, Aga Khan University14, New Generation University College15, Public Health Foundation of India16, Duy Tan University17, Centers for Disease Control and Prevention18, Bielefeld University19, Swiss Tropical and Public Health Institute20, Imperial College London21, University of Basel22, Baylor College of Medicine23, Boston Children's Hospital24, Yonsei University25, Tehran University of Medical Sciences26, Jordan University of Science and Technology27, University of London28, University of Melbourne29, University of Liverpool30, Aintree University Hospitals NHS Foundation Trust31, Martin Luther University of Halle-Wittenberg32, United Nations Population Fund33, Iran University of Medical Sciences34, University of Ulm35, University of Sydney36, University of Porto37, University of British Columbia38, A.T. Still University39, Golestan University40, Harvard University41, Case Western Reserve University42, Marshall University43, University of KwaZulu-Natal44, Utkal University45, AIIMS, New Delhi46, Haramaya University47, Queensland University of Technology48, Jagiellonian University Medical College49, Wrocław Medical University50, Johns Hopkins University51, Hanoi Medical University52, National Research University – Higher School of Economics53, Norwegian Institute of Public Health54, University of Bergen55, University of Tromsø56, Karolinska Institutet57, Kyoto University58, Jackson State University59, Wuhan University60, University of Washington61
TL;DR: In this article, the authors report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol, and an “other” group that encompasses residual causes.
Abstract: Importance Liver cancer is among the leading causes of cancer deaths globally. The most common causes for liver cancer include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol use. Objective To report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to HBV, HCV, alcohol, and an “other” group that encompasses residual causes. Design, Settings, and Participants Mortality was estimated using vital registration and cancer registry data in an ensemble modeling approach. Single-cause mortality estimates were adjusted for all-cause mortality. Incidence was derived from mortality estimates and the mortality-to-incidence ratio. Through a systematic literature review, data on the proportions of liver cancer due to HBV, HCV, alcohol, and other causes were identified. Years of life lost were calculated by multiplying each death by a standard life expectancy. Prevalence was estimated using mortality-to-incidence ratio as surrogate for survival. Total prevalence was divided into 4 sequelae that were multiplied by disability weights to derive years lived with disability (YLDs). DALYs were the sum of years of life lost and YLDs. Main Outcomes and Measures Liver cancer mortality, incidence, YLDs, years of life lost, DALYs by etiology, age, sex, country, and year. Results There were 854 000 incident cases of liver cancer and 810 000 deaths globally in 2015, contributing to 20 578 000 DALYs. Cases of incident liver cancer increased by 75% between 1990 and 2015, of which 47% can be explained by changing population age structures, 35% by population growth, and −8% to changing age-specific incidence rates. The male-to-female ratio for age-standardized liver cancer mortality was 2.8. Globally, HBV accounted for 265 000 liver cancer deaths (33%), alcohol for 245 000 (30%), HCV for 167 000 (21%), and other causes for 133 000 (16%) deaths, with substantial variation between countries in the underlying etiologies. Conclusions and Relevance Liver cancer is among the leading causes of cancer deaths in many countries. Causes of liver cancer differ widely among populations. Our results show that most cases of liver cancer can be prevented through vaccination, antiviral treatment, safe blood transfusion and injection practices, as well as interventions to reduce excessive alcohol use. In line with the Sustainable Development Goals, the identification and elimination of risk factors for liver cancer will be required to achieve a sustained reduction in liver cancer burden. The GBD study can be used to guide these prevention efforts.
1,208 citations
TL;DR: After standard neoadjuvant chemotherapy containing anthracycline, taxane, or both, the addition of adjuvant capecitabine therapy was safe and effective in prolonging disease‐free survival and overall survival among patients with HER2‐negative breast cancer who had residual invasive disease on pathological testing.
Abstract: BackgroundPatients who have residual invasive carcinoma after the receipt of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)–negative breast cancer have poor prognoses. The benefit of adjuvant chemotherapy in these patients remains unclear. MethodsWe randomly assigned 910 patients with HER2-negative residual invasive breast cancer after neoadjuvant chemotherapy (containing anthracycline, taxane, or both) to receive standard postsurgical treatment either with capecitabine or without (control). The primary end point was disease-free survival. Secondary end points included overall survival. ResultsThe result of the prespecified interim analysis met the primary end point, so this trial was terminated early. The final analysis showed that disease-free survival was longer in the capecitabine group than in the control group (74.1% vs. 67.6% of the patients were alive and free from recurrence or second cancer at 5 years; hazard ratio for recurrence, second cancer, or death, 0.70; 95% ...
1,066 citations
TL;DR: Abemaciclib at 150 mg twice daily plus fulvestrant was effective, significantly improving PFS and ORR and demonstrating a tolerable safety profile in women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who progressed while receiving ET.
Abstract: PurposeMONARCH 2 (ClinicalTrialsgov identifier: NCT02107703) compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, plus fulvestrant with fulvestrant alone in patients with advanced breast cancer (ABC)Patients and MethodsMONARCH 2 was a global, double-blind, phase III study of women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who had progressed while receiving neoadjuvant or adjuvant endocrine therapy (ET), ≤ 12 months from the end of adjuvant ET, or while receiving first-line ET for metastatic disease Patients were randomly assigned 2:1 to receive abemaciclib or placebo (150 mg twice daily) on a continuous schedule and fulvestrant (500 mg, per label) The primary end point was investigator-assessed progression-free survival (PFS), and key secondary end points included overall survival, objective response rate (ORR), duration of response, clinical benefit rate, quality of life, and safetyResultsBetween August
1,012 citations
TL;DR: Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.
Abstract: PurposeAbemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer previously treated with endocrine therapy.MethodsMONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events.ResultsMedian progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95...
977 citations
University of Waterloo1, University of Melbourne2, Complutense University of Madrid3, Massachusetts Eye and Ear Infirmary4, University of California, Los Angeles5, University of Düsseldorf6, University of São Paulo7, Yonsei University8, Federal University of São Paulo9, Fudan University Shanghai Medical College10, Aston University11, University of Auckland12
TL;DR: It became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size.
Abstract: The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.
785 citations
TL;DR: The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT and can support clinical decision making for treatment duration.
773 citations
TL;DR: The epidemiological trend of obesity in Asia is reviewed, with special emphasis on the emerging condition of non-alcoholic fatty liver disease (NAFLD), and pharmacological agents have entered phase III development for steatohepatitis.
Leipzig University1, Shanghai Jiao Tong University2, Iuliu Hațieganu University of Medicine and Pharmacy3, Yonsei University4, University of Paris5, University of Pavia6, University of Malaya7, The Chinese University of Hong Kong8, University of Calgary9, Hiroshima University10, Goethe University Frankfurt11, Paris Diderot University12
TL;DR: CAP provides a standardized non-invasive measure of hepatic steatosis and factors such as the underlying disease, BMI and diabetes must be taken into account when interpreting CAP.
National University of Singapore1, Khon Kaen University2, Duke University3, Singapore General Hospital4, University of Tokyo5, Harvard University6, Chang Gung University7, Sun Yat-sen University8, Southern Medical University9, Federal University of São Paulo10, Yonsei University11, Los Alamos National Laboratory12
TL;DR: In this paper, the authors analyzed 489 cholangiocarcinoma (CCA) from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information.
Abstract: Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters-fluke-positive CCAs (clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations; conversely, fluke-negative CCAs (clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements. Whole-genome analysis highlighted FGFR2 3' untranslated region deletion as a mechanism of FGFR2 upregulation. Integration of noncoding promoter mutations with protein-DNA binding profiles demonstrates pervasive modulation of H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores-mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Our results exemplify how genetics, epigenetics, and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer.Significance: Integrated whole-genome and epigenomic analysis of CCA on an international scale identifies new CCA driver genes, noncoding promoter mutations, and structural variants. CCA molecular landscapes differ radically by etiology, underscoring how distinct cancer subtypes in the same organ may arise through different extrinsic and intrinsic carcinogenic processes. Cancer Discov; 7(10); 1116-35. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 1047.
University of Melbourne1, Université libre de Bruxelles2, Katholieke Universiteit Leuven3, University of Victoria4, St. Vincent's Health System5, La Trobe University6, Royal Melbourne Hospital7, Netherlands Cancer Institute8, University of California, San Diego9, Vanderbilt University10, Peter MacCallum Cancer Centre11, University of Antwerp12, French Institute of Health and Medical Research13, University of Paris14, Medical University of Vienna15, Cornell University16, University of Texas MD Anderson Cancer Center17, Mayo Clinic18, University of Queensland19, Royal Brisbane and Women's Hospital20, Harvard University21, Novartis22, Indiana University – Purdue University Indianapolis23, Fred Hutchinson Cancer Research Center24, University of Milan25, University of Auvergne26, Kansai Medical University27, Yeshiva University28, Yonsei University29, Rhode Island Hospital30, Brown University31, Curie Institute32, Charité33, Yale University34, University of British Columbia35, Garvan Institute of Medical Research36, Université Paris-Saclay37, Autonomous University of Madrid38, University of Ottawa39, National Institutes of Health40, New York University41, University of Adelaide42, Stanford University43, Anschutz Medical Campus44, University of Padua45, European Organisation for Research and Treatment of Cancer46, Medical University of Graz47, Hoffmann-La Roche48, Genentech49, MedImmune50, Merck & Co.51, Memorial Sloan Kettering Cancer Center52
TL;DR: Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.
Abstract: Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.
TL;DR: A cohort of participants who participated in health screening programmes provided by the NHIS in the Republic of Korea to offer relevant and useful data for health researchers, especially in the field of non-communicable diseases and health risk factors, and policy-maker.
Abstract: Purpose The National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) is a cohort of participants who participated in health screening programmes provided by the NHIS in the Republic of Korea The NHIS constructed the NHIS-HEALS cohort database in 2015 The purpose of this cohort is to offer relevant and useful data for health researchers, especially in the field of non-communicable diseases and health risk factors, and policy-maker Participants To construct the NHIS-HEALS database, a sample cohort was first selected from the 2002 and 2003 health screening participants, who were aged between 40 and 79 in 2002 and followed up through 2013 This cohort included 514 866 health screening participants who comprised a random selection of 10% of all health screening participants in 2002 and 2003 Findings to date The age-standardised prevalence of anaemia, diabetes mellitus, hypertension, obesity, hypercholesterolaemia and abnormal urine protein were 98%, 82%, 356%, 27%, 142% and 20%, respectively The age-standardised mortality rate for the first 2 years (through 2004) was 4420 per 100 000 person-years, while the rate for 10 years (through 2012) was 8659 per 100 000 person-years The most common cause of death was malignant neoplasm in both sexes (3641 per 100 000 person-years for men, 1283 per 100 000 person-years for women) Future plans This database can be used to study the risk factors of non-communicable diseases and dental health problems, which are important health issues that have not yet been fully investigated The cohort will be maintained and continuously updated by the NHIS
TL;DR: This review discusses various metal-organic cooperative catalytic systems developed for C-H and C-C bond activation reactions, which proceed with high efficiencies and selectivities.
Abstract: Transition-metal-catalyzed activation of C–H and C–C bonds is a challenging area in synthetic organic chemistry. Among various methods to accomplish these processes, the approach using metal–organic cooperative catalytic systems is one of the most promising. In this protocol, organic molecules as well as transition metals act as catalysts to bring about reactions, which proceed with high efficiencies and selectivities. Various metal–organic cooperative catalytic systems developed for C–H and C–C bond activation reactions are discussed in this review. Also discussed are how each metal–organic cooperative catalyst affects the reaction mechanism and what kinds of substrates can be applied in each of the catalytic processes.
TL;DR: These techniques are proving to be promising for the extraction of thermolabile phenolic compounds due to their advantages over conventional, time-consuming, and laborious extraction techniques, such as reduced solvent use and time and energy consumption and higher recovery rates with lower operational costs.
Abstract: Polyphenols as phytochemicals have gained significant importance owing to several associated health benefits with regard to lifestyle diseases and oxidative stress. To date, the development of a single standard method for efficient and rapid extraction of polyphenols from plant matrices has remained a challenge due to the inherent limitations of various conventional extraction methods. The exploitation of polyphenols as bioactive compounds at various commercial levels has motivated scientists to explore more eco-friendly, efficient, and cost-effective extraction techniques, based on a green extraction approach. The current review aims to provide updated technical information about extraction mechanisms, their advantages and disadvantages, and factors affecting efficiencies, and also presents a comparative overview of applications of the following modern green extraction techniques-supercritical fluid extraction, ultrasound-assisted extraction, microwave-assisted extraction, pressurized liquid extraction, and pressurized hot water extraction-as alternatives to conventional extraction methods for polyphenol extraction. These techniques are proving to be promising for the extraction of thermolabile phenolic compounds due to their advantages over conventional, time-consuming, and laborious extraction techniques, such as reduced solvent use and time and energy consumption and higher recovery rates with lower operational costs. The growing interest in plant-derived polyphenols prompts continual search for green and economically feasible modern extraction techniques. Modern green extraction techniques represent promising approaches by virtue of overcoming current limitations to the exploitation of polyphenols as bioactive compounds to explore their wide-reaching applications on an industrial scale and in emerging global markets. Future research is needed in order to remove the technical barriers to scale-up the processes for industrial needs by increasing our understanding and improving the design of modern extraction operations.
TL;DR: In this paper, a planar-architecture perovskite solar cell with a power conversion efficiency of 10.0% has been proposed for next-generation photovoltaics.
Abstract: Thermally unstable nature of hybrid organic–inorganic perovskites has been a major obstacle to fabricating the long-term operational device. A cesium lead halide perovskite has been suggested as an alternative light absorber, due to its superb thermal stability. However, the phase instability and poor performance are hindering the further progress. Here, cesium lead halide perovskite solar cells with enhanced performance and stability are demonstrated via incorporating potassium cations. Based on Cs0.925K0.075PbI2Br, the planar-architecture device achieves a power conversion efficiency of 10.0%, which is a remarkable record in the field of inorganic perovskite solar cells. In addition, the device shows an extended operational lifetime against air. Our research will stimulate the development of cesium lead halide perovskite materials for next-generation photovoltaics.
University of Melbourne1, Université libre de Bruxelles2, Katholieke Universiteit Leuven3, St. Vincent's Health System4, La Trobe University5, Royal Melbourne Hospital6, Netherlands Cancer Institute7, University of California, San Diego8, Vanderbilt University9, Peter MacCallum Cancer Centre10, French Institute of Health and Medical Research11, University of Paris12, Medical University of Vienna13, Cornell University14, University of Texas MD Anderson Cancer Center15, Mayo Clinic16, University of Queensland17, Royal Brisbane and Women's Hospital18, Harvard University19, Novartis20, Indiana University – Purdue University Indianapolis21, Fred Hutchinson Cancer Research Center22, University of Milan23, University of Auvergne24, Kansai Medical University25, Yeshiva University26, Yonsei University27, Brown University28, Rhode Island Hospital29, Curie Institute30, Charité31, Yale University32, University of British Columbia33, University of Victoria34, Garvan Institute of Medical Research35, Université Paris-Saclay36, Autonomous University of Madrid37, University of Ottawa38, National Institutes of Health39, New York University40, University of Adelaide41, Stanford University42, Anschutz Medical Campus43, University of Padua44, European Organisation for Research and Treatment of Cancer45, Medical University of Graz46, Hoffmann-La Roche47, Genentech48, MedImmune49, Merck & Co.50, Memorial Sloan Kettering Cancer Center51
TL;DR: In this paper, a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors on hematoxylin and eosin sections, in both primary and metastatic settings, was proposed.
Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment. We propose a standardized methodology to assess TILs in solid tumors on hematoxylin and eosin sections, in both primary and metastatic settings, based on the International Immuno-Oncology Biomarker Working Group guidelines for TIL assessment in invasive breast carcinoma. A review of the literature regarding the value of TIL assessment in different solid tumor types follows in part 2. The method we propose is reproducible, affordable, easily applied, and has demonstrated prognostic and predictive significance in invasive breast carcinoma. This standardized methodology may be used as a reference against which other methods are compared, and should be evaluated for clinical validity and utility. Standardization of TIL assessment will help to improve consistency and reproducibility in this field, enrich both the quality and quantity of comparable evidence, and help to thoroughly evaluate the utility of TILs assessment in this era of immunotherapy.
TL;DR: This study is the largest to provide CMR specific reference ranges for left ventricular, right ventricular), left atrial and right atrial structure and function derived from truly healthy Caucasian adults aged 45–74.
Abstract: Cardiovascular magnetic resonance (CMR) is the gold standard method for the assessment of cardiac structure and function. Reference ranges permit differentiation between normal and pathological states. To date, this study is the largest to provide CMR specific reference ranges for left ventricular, right ventricular, left atrial and right atrial structure and function derived from truly healthy Caucasian adults aged 45–74. Five thousand sixty-five UK Biobank participants underwent CMR using steady-state free precession imaging at 1.5 Tesla. Manual analysis was performed for all four cardiac chambers. Participants with non-Caucasian ethnicity, known cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Remaining participants formed the healthy reference cohort; reference ranges were calculated and were stratified by gender and age (45–54, 55–64, 65–74). After applying exclusion criteria, 804 (16.2%) participants were available for analysis. Left ventricular (LV) volumes were larger in males compared to females for absolute and indexed values. With advancing age, LV volumes were mostly smaller in both sexes. LV ejection fraction was significantly greater in females compared to males (mean ± standard deviation [SD] of 61 ± 5% vs 58 ± 5%) and remained static with age for both genders. In older age groups, LV mass was lower in men, but remained virtually unchanged in women. LV mass was significantly higher in males compared to females (mean ± SD of 53 ± 9 g/m2 vs 42 ± 7 g/m2). Right ventricular (RV) volumes were significantly larger in males compared to females for absolute and indexed values and were smaller with advancing age. RV ejection fraction was higher with increasing age in females only. Left atrial (LA) maximal volume and stroke volume were significantly larger in males compared to females for absolute values but not for indexed values. LA ejection fraction was similar for both sexes. Right atrial (RA) maximal volume was significantly larger in males for both absolute and indexed values, while RA ejection fraction was significantly higher in females. We describe age- and sex-specific reference ranges for the left ventricle, right ventricle and atria in the largest validated normal Caucasian population.
TL;DR: The first measurement of the tau lepton polarization P-tau(D*) in the decay (B) over bar -> D* tau(-) (v) over b (tau) as well as a new measurement of the ratio of the branching fractions was reported in this paper.
Abstract: We report the first measurement of the tau lepton polarization P-tau(D*) in the decay (B) over bar -> D* tau(-) (v) over bar (tau) as well as a newmeasurement of the ratio of the branching fractions R(D*) = B((B) over bar -> D* tau(-) (v) over bar (tau)) / B((B) over bar -> D* l(-) (v) over bar (l)), where l(-) denotes an electron or a muon, and the tau is reconstructed in the modes tau(-) -> pi(-) v(tau) and tau(-) -> rho(-) v(tau). We use the full data sample of 772 x 10(6) B (B) over bar pairs recorded with the Belle detector at the (KEKB) over bar electron-positron collider. Our results, P-tau(D*) = -0.38 +/- 0.51 (stat)(-0.16)(+0.21) (syst) and R(D*) = 0.270 +/- 0.035 (stat)(- 0.025)(+0.028) (syst), are consistent with the theoretical predictions of the standard model.
TL;DR: A blind image evaluator based on a convolutional neural network (BIECON) is proposed that follows the FR-IQA behavior using the local quality maps as intermediate targets for conventional neural networks, which leads to NR- IQA prediction accuracy that is comparable with that of state-of-the-art FR-iqA methods.
Abstract: In general, owing to the benefits obtained from original information, full-reference image quality assessment (FR-IQA) achieves relatively higher prediction accuracy than no-reference image quality assessment (NR-IQA). By fully utilizing reference images, conventional FR-IQA methods have been investigated to produce objective scores that are close to subjective scores. In contrast, NR-IQA does not consider reference images; thus, its performance is inferior to that of FR-IQA. To alleviate this accuracy discrepancy between FR-IQA and NR-IQA methods, we propose a blind image evaluator based on a convolutional neural network (BIECON). To imitate FR-IQA behavior, we adopt the strong representation power of a deep convolutional neural network to generate a local quality map, similar to FR-IQA. To obtain the best results from the deep neural network, replacing hand-crafted features with automatically learned features is necessary. To apply the deep model to the NR-IQA framework, three critical problems must be resolved: 1) lack of training data; 2) absence of local ground truth targets; and 3) different purposes of feature learning. BIECON follows the FR-IQA behavior using the local quality maps as intermediate targets for conventional neural networks, which leads to NR-IQA prediction accuracy that is comparable with that of state-of-the-art FR-IQA methods.
Keio University1, Kyoto Prefectural University of Medicine2, Tokyo Dental College3, Kyorin University4, Korea University5, University of Ulsan6, Seoul National University7, Chonnam National University8, Yonsei University9, Wenzhou Medical College10, Sun Yat-sen University11, Peking University12, Xiamen University13
TL;DR: The concept of Tear Film Oriented Therapy (TFOT), which evolved from the definition of dry eye, emphasizing the importance of a stable tear film, is discussed.
Abstract: For the last 20 years, a great amount of evidence has accumulated through epidemiological studies that most of the dry eye disease encountered in daily life, especially in video display terminal (VDT) workers, involves short tear film breakup time (TFBUT) type dry eye, a category characterized by severe symptoms but minimal clinical signs other than short TFBUT. An unstable tear film also affects the visual function, possibly due to the increase of higher order aberrations. Based on the change in the understanding of the types, symptoms, and signs of dry eye disease, the Asia Dry Eye Society agreed to the following definition of dry eye: "Dry eye is a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage." The definition stresses instability of the tear film as well as the importance of visual impairment, highlighting an essential role for TFBUT assessment. This paper discusses the concept of Tear Film Oriented Therapy (TFOT), which evolved from the definition of dry eye, emphasizing the importance of a stable tear film.
TL;DR: A convolutional neural network model, named FDC-CNN, is proposed, in which a receptive field tailored to multivariate sensor signals slides along the time axis, to extract fault features, making it possible to locate the variable and time information that represents process faults.
Abstract: Many studies on the prediction of manufacturing results using sensor signals have been conducted in the field of fault detection and classification (FDC) for semiconductor manufacturing processes. However, fault diagnosis used to find clues as to root causes remains a challenging area. In particular, process monitoring using neural networks has been employed to only a limited extent because it is a black box model, making the relationships between input data and output results difficult to interpret in actual manufacturing settings, despite its high classification performance. In this paper, we propose a convolutional neural network (CNN) model, named FDC-CNN, in which a receptive field tailored to multivariate sensor signals slides along the time axis, to extract fault features. This approach enables the association of the output of the first convolutional layer with the structural meaning of the raw data, making it possible to locate the variable and time information that represents process faults. In an experiment on a chemical vapor deposition process, the proposed method outperformed other deep learning models.
TL;DR: The trastuzumab emtansine 2·4 mg/kg weekly group had lower incidences of grade 3 or more adverse events than did taxane treatment and the primary endpoint (overall survival) was assessed in the intention-to-treat population.
Abstract: Summary Background Although trastuzumab plus chemotherapy is the standard of care for first-line treatment of HER2-positive advanced gastric cancer, there is no established therapy in the second-line setting. In GATSBY, we examined the efficacy and tolerability of trastuzumab emtansine in patients previously treated for HER2-positive advanced gastric cancer (unresectable, locally advanced, or metastatic gastric cancer, including adenocarcinoma of the gastro-oesophageal junction). Methods This is the final analysis from GATSBY, a randomised, open-label, adaptive, phase 2/3 study, done at 107 centres (28 countries worldwide). Eligible patients had HER2-positive advanced gastric cancer and progressed during or after first-line therapy. In stage one of the trial, patients were randomly assigned to treatment groups (2:2:1) to receive intravenous trastuzumab emtansine (3·6 mg/kg every 3 weeks or 2·4 mg/kg weekly) or physician's choice of a taxane (intravenous docetaxel 75 mg/m 2 every 3 weeks or intravenous paclitaxel 80 mg/m 2 weekly). In stage two, patients were randomly assigned to treatment groups (2:1) to receive the independent data monitoring committee (IDMC)-selected dose of trastuzumab emtansine (2·4 mg/kg weekly) or a taxane (same regimen as above). We used permuted block randomisation, stratified by world region, previous HER2-targeted therapy, and previous gastrectomy. The primary endpoint (overall survival) was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01641939. Findings Between Sept 3, 2012, and Oct 14, 2013, 70 patients were assigned to receive trastuzumab emtansine 3·6 mg/kg every 3 weeks, 75 to receive trastuzumab emtansine 2·4 mg/kg weekly, and 37 to receive a taxane in the stage 1 part of the trial. At the pre-planned interim analysis (Oct 14, 2013), the IDMC selected trastuzumab emtansine 2·4 mg/kg weekly as the dose to proceed to stage 2. By Feb 9, 2015, a further 153 patients had been randomly assigned to receive trastuzumab emtansine 2·4 mg/kg weekly and a further 80 to receive a taxane. At data cutoff, median follow-up was 17·5 months (IQR 12·1–23·0) for the trastuzumab emtansine 2·4 mg/kg weekly group and 15·4 months (9·2–18·1) in the taxane group. Median overall survival was 7·9 months (95% CI 6·7–9·5) with trastuzumab emtansine 2·4 mg/kg weekly and 8·6 months (7·1–11·2) with taxane treatment (hazard ratio 1·15, 95% CI 0·87–1·51, one-sided p=0·86). The trastuzumab emtansine 2·4 mg/kg group had lower incidences of grade 3 or more adverse events (134 [60%] of 224 patients treated with trastuzumab emtansine vs 78 [70%] of 111 patients treated with a taxane), and similar incidences of adverse events leading to death (eight [4%] vs four [4%]), serious adverse events (65 [29%] vs 31 [28%]), and adverse events leading to treatment discontinuation (31 [14%] vs 15 [14%]) than did taxane treatment. The most common grade 3 or more adverse events in the trastuzumab emtansine 2·4 mg/kg weekly group were anaemia (59 [26%]) and thrombocytopenia (25 [11%]) compared with neutropenia (43 [39%]), and anaemia (20 [18%]), in the taxane group. The most common serious adverse events were anaemia (eight [4%]), upper gastrointestinal haemorrhage (eight [4%]), pneumonia (seven [3%]), gastric haemorrhage (six [3%]), and gastrointestinal haemorrhage (five [2%]) in the trastuzumab emtansine 2·4 mg/kg weekly group compared with pneumonia (four [4%]), febrile neutropenia (four [4%]), anaemia (three [3%]), and neutropenia (three [3%]) in the taxane group. Interpretation Trastuzumab emtansine was not superior to taxane in patients with previously treated, HER2-positive advanced gastric cancer. There is still an unmet need in this patient group and therapeutic options remain limited. Funding F Hoffmann-La Roche.
TL;DR: The result is consistent with standard model (SM) expectations, where the largest discrepancy from a SM prediction is observed in the muon modes with a local significance of 2.6σ.
Abstract: We present a measurement of angular observables and a test of lepton flavor universality in the B -> K(+)l(+)l(-) decay, where l is either e or mu. The analysis is performed on a data sample corresponding to an integrated luminosity of 711 fb(-1) containing 772 x 10(6) B (B) over bar pairs, collected at the Upsilon(4S) resonance with the Belle detector at the asymmetric-energy e(+)e(-) collider KEKB. The result is consistent with standard model (SM) expectations, where the largest discrepancy from a SM prediction is observed in the muon modes with a local significance of 2.6 sigma.
TL;DR: The role of NETs in the pathogenesis of autoimmune diseases and the possibility of using targeted therapies directed to NETs and associated molecules to treat autoimmune diseases are described.
TL;DR: In this article, the role of the support may have a significant effect on the catalytic properties, similar to that of the ligand molecules in homogeneous catalysts, and the support effect was demonstrated by preparing a single-atom platinum catalyst on two different supports.
Abstract: Single-atom catalysts (SACs) provide an ideal platform for reducing noble-metal usage. SACs also exhibit unusual catalytic properties due to the absence of a metal surface. The role of the support may have a significant effect on the catalytic properties, similar to that of the ligand molecules in homogeneous catalysts. Here, the support effect was demonstrated by preparing a single-atom platinum catalyst on two different supports: titanium carbide (Pt1/TiC) and titanium nitride (Pt1/TiN). The formation of single-atom Pt was confirmed by STEM, EXAFS, and in situ IR spectroscopy. Pt1/TiC showed higher activity, selectivity, and stability for electrochemical H2O2 production than Pt1/TiN. Density functional theory calculations presented that oxygen species have strong affinity into Pt1/TiN, possibly acting as surface poisoning species, and Pt1/TiC preserves oxygen–oxygen bonds more with higher selectivity toward H2O2 production. This work clearly shows that the support in SACs actively participates in the su...
TL;DR: A smart fluorescent probe containing a crown ether moiety could be developed as a sensor for metal ions, anions and other bio-molecules and be further applied to monitor the relevant biological process in vivo.
Abstract: Crown ethers, discovered by the winner of the Nobel Prize Charles Pedersen, are cyclic chemical compounds that consist of a ring or multiple rings containing several ether groups that are capable of binding alkali ions. A smart fluorescent probe containing a crown ether moiety could be developed as a sensor for metal ions, anions and other bio-molecules and be further applied to monitor the relevant biological process in vivo. This review highlights recent advances which can be divided into seven parts: (i) fluorescent probes containing a simple crown ether or an aza-crown ether structure; (ii) fluorescent probes containing an azathia crown ether; (iii) fluorescent probes containing a cryptand; (iv) fluorescent probes containing two or more binding sites; (v) crown ether derivatives-metal complex assisted chemosensing of bioactive species; (vi) crown ether-based chemosensors for bioactive molecular detection; and (vii) efforts to improve biological relevance.
01 Oct 2017
TL;DR: This paper proposes novel ensemble Temporal Sliding LSTM (TS-LSTM) networks for skeleton-based action recognition and analyzes a relation between the recognized actions and the multi-term TS-L STM features by visualizing the softmax features of multiple parts.
Abstract: This paper addresses the problems of feature representation of skeleton joints and the modeling of temporal dynamics to recognize human actions. Traditional methods generally use relative coordinate systems dependent on some joints, and model only the long-term dependency, while excluding short-term and medium term dependencies. Instead of taking raw skeletons as the input, we transform the skeletons into another coordinate system to obtain the robustness to scale, rotation and translation, and then extract salient motion features from them. Considering that Long Shortterm Memory (LSTM) networks with various time-step sizes can model various attributes well, we propose novel ensemble Temporal Sliding LSTM (TS-LSTM) networks for skeleton-based action recognition. The proposed network is composed of multiple parts containing short-term, mediumterm and long-term TS-LSTM networks, respectively. In our network, we utilize an average ensemble among multiple parts as a final feature to capture various temporal dependencies. We evaluate the proposed networks and the additional other architectures to verify the effectiveness of the proposed networks, and also compare them with several other methods on five challenging datasets. The experimental results demonstrate that our network models achieve the state-of-the-art performance through various temporal features. Additionally, we analyze a relation between the recognized actions and the multi-term TS-LSTM features by visualizing the softmax features of multiple parts.