Showing papers by "University of Duisburg-Essen published in 2018"
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Clotilde Théry1, Kenneth W. Witwer2, Elena Aikawa3, María José Alcaraz4 +414 more•Institutions (209)
TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
5,988 citations
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TL;DR: This work presents a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and shows that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods.
Abstract: Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.
1,620 citations
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Verneri Anttila1, Verneri Anttila2, Brendan Bulik-Sullivan2, Brendan Bulik-Sullivan1 +717 more•Institutions (270)
TL;DR: It is demonstrated that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine, and it is shown that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures.
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
1,357 citations
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Université Paris-Saclay1, Netherlands Cancer Institute2, University of Siena3, University of Sydney4, University of Queensland5, Peter MacCallum Cancer Centre6, Alfred Hospital7, University of Western Australia8, The Royal Marsden NHS Foundation Trust9, Curie Institute10, University of Duisburg-Essen11, Radboud University Nijmegen Medical Centre12, Hannover Medical School13, Université de Montréal14, Washington University in St. Louis15, Merck & Co.16
TL;DR: As adjuvant therapy for high‐risk stage III melanoma, 200 mg of pembrolizumab administered every 3 weeks for up to 1 year resulted in significantly longer recurrence‐free survival than placebo, with no new toxic effects identified.
Abstract: Background The programmed death 1 (PD-1) inhibitor pembrolizumab has been found to prolong progression-free and overall survival among patients with advanced melanoma. We conducted a phase 3 double-blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected, high-risk stage III melanoma. Methods Patients with completely resected stage III melanoma were randomly assigned (with stratification according to cancer stage and geographic region) to receive 200 mg of pembrolizumab (514 patients) or placebo (505 patients) intravenously every 3 weeks for a total of 18 doses (approximately 1 year) or until disease recurrence or unacceptable toxic effects occurred. Recurrence-free survival in the overall intention-to-treat population and in the subgroup of patients with cancer that was positive for the PD-1 ligand (PD-L1) were the primary end points. Safety was also evaluated. Results At a median follow-up of 15 months, pembrolizumab was associated with significantly longer recurrence...
1,225 citations
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Susanne Gröbner1, Barbara C. Worst, Joachim Weischenfeldt2, Joachim Weischenfeldt3 +182 more•Institutions (23)
TL;DR: The data suggest that 7–8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.
Abstract: Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.
958 citations
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University of Texas MD Anderson Cancer Center1, University of Melbourne2, Harvard University3, Royal North Shore Hospital4, University of Kiel5, University of Colorado Denver6, University of South Florida7, Washington University in St. Louis8, Sir Charles Gairdner Hospital9, Stanford University10, Memorial Sloan Kettering Cancer Center11, University of Queensland12, University of Duisburg-Essen13, Regeneron14, University of Arizona15, Autonomous University of Barcelona16, Sarah Cannon Research Institute17, Emory University18
TL;DR: Among patients with advanced cutaneous squamous‐cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors.
Abstract: Background No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma. Methods We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review. Results In the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval [CI], 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event. Conclusions Among patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT02383212 and NCT02760498 .).
876 citations
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TL;DR: Among men with nonmetastatic castration‐resistant prostate cancer, metastasis‐free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo.
Abstract: Background Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. Methods We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death. Results A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after ...
863 citations
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TL;DR: A resistance program expressed by malignant cells that is associated with T cell exclusion and immune evasion is identified, and this study provides a high-resolution landscape of ICI-resistant cell states, identifies clinically predictive signatures, and suggests new therapeutic strategies to overcome immunotherapy resistance.
794 citations
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TL;DR: The present Bioconda, a distribution of bioinformatics software for the lightweight, multi-platform and language-agnostic package manager Conda, improves analysis reproducibility by allowing users to define isolated environments with defined software versions.
Abstract: We present Bioconda (https://bioconda.github.io), a distribution of bioinformatics software for the lightweight, multi-platform and language-agnostic package manager Conda. Currently, Bioconda offers a collection of over 3000 software packages, which is continuously maintained, updated, and extended by a growing global community of more than 200 contributors. Bioconda improves analysis reproducibility by allowing users to define isolated environments with defined software versions, all of which are easily installed and managed without administrative privileges.
699 citations
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University of Pittsburgh1, University of Texas MD Anderson Cancer Center2, Stanford University3, University of Milan4, Institute of Cancer Research5, University of Duisburg-Essen6, University of Chicago7, Institut Gustave Roussy8, University of Michigan9, Emory University10, Harvard University11, University of Zurich12, Kobe University13, Bristol-Myers Squibb14
TL;DR: Nivolumab significantly improved OS at the primary analysis and demonstrated prolonged OS benefit vs IC and maintenance of a manageable and consistent safety profile with 2-year follow-up.
523 citations
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TL;DR: The authors provide an overview of research into social media rumours with the ultimate goal of developing a rumour classification system that consists of four components: rumour detection, rumor tracking, rumour stance classification, and rumour veracity classification.
Abstract: Despite the increasing use of social media platforms for information and news gathering, its unmoderated nature often leads to the emergence and spread of rumours, i.e., items of information that are unverified at the time of posting. At the same time, the openness of social media platforms provides opportunities to study how users share and discuss rumours, and to explore how to automatically assess their veracity, using natural language processing and data mining techniques. In this article, we introduce and discuss two types of rumours that circulate on social media: long-standing rumours that circulate for long periods of time, and newly emerging rumours spawned during fast-paced events such as breaking news, where reports are released piecemeal and often with an unverified status in their early stages. We provide an overview of research into social media rumours with the ultimate goal of developing a rumour classification system that consists of four components: rumour detection, rumour tracking, rumour stance classification, and rumour veracity classification. We delve into the approaches presented in the scientific literature for the development of each of these four components. We summarise the efforts and achievements so far toward the development of rumour classification systems and conclude with suggestions for avenues for future research in social media mining for the detection and resolution of rumours.
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TL;DR: An extended and structured literature analysis is conducted through which the most important challenges for researchers are discussed and potential solutions proposed and used to extend an existing framework on social media analytics.
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TL;DR: There is an emerging quest for lightweight materials with excellent mechanical properties and economic production, while still being sustainable and functionalizable, which could form the basis of the future bio economy for energy and material efficiency.
Abstract: There is an emerging quest for lightweight materials with excellent mechanical properties and economic production, while still being sustainable and functionalizable. They could form the basis of the future bioeconomy for energy and material efficiency. Cellulose has long been recognized as an abundant polymer. Modified celluloses were, in fact, among the first polymers used in technical applications; however, they were later replaced by petroleum-based synthetic polymers. Currently, there is a resurgence of interest to utilize renewable resources, where cellulose is foreseen to make again a major impact, this time in the development of advanced materials. This is because of its availability and properties, as well as economic and sustainable production. Among cellulose-based structures, cellulose nanofibrils and nanocrystals display nanoscale lateral dimensions and lengths ranging from nanometers to micrometers. Their excellent mechanical properties are, in part, due to their crystalline assembly via hydrogen bonds. Owing to their abundant surface hydroxyl groups, they can be easily modified with nanoparticles, (bio)polymers, inorganics, or nanocarbons to form functional fibers, films, bulk matter, and porous aerogels and foams. Here, some of the recent progress in the development of advanced materials within this rapidly growing field is reviewed.
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Raymond K. Walters1, Raymond K. Walters2, Renato Polimanti3, Emma C. Johnson4 +168 more•Institutions (48)
TL;DR: The largest genome-wide association study to date of DSM-IV-diagnosed AD found loci associated with AD and characterized the relationship between AD and other psychiatric and behavioral outcomes, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.
Abstract: Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10-13) and African ancestries (rs2066702; P = 2.2 × 10-9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.
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TL;DR: This study uniformly analyzed whole-exome sequencing of 249 tumors and matched normal tissue from patients with clinically annotated outcomes to immune checkpoint therapy across multiple cancer types to examine additional tumor genomic features that contribute to selective response.
Abstract: Tumor mutational burden correlates with response to immune checkpoint blockade in multiple solid tumors, although in microsatellite-stable tumors this association is of uncertain clinical utility. Here we uniformly analyzed whole-exome sequencing (WES) of 249 tumors and matched normal tissue from patients with clinically annotated outcomes to immune checkpoint therapy, including radiographic response, across multiple cancer types to examine additional tumor genomic features that contribute to selective response. Our analyses identified genomic correlates of response beyond mutational burden, including somatic events in individual driver genes, certain global mutational signatures, and specific HLA-restricted neoantigens. However, these features were often interrelated, highlighting the complexity of identifying genetic driver events that generate an immunoresponsive tumor environment. This study lays a path forward in analyzing large clinical cohorts in an integrated and multifaceted manner to enhance the ability to discover clinically meaningful predictive features of response to immune checkpoint blockade.
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TL;DR: Efficient terahertz harmonic generation—challenging but important for ultrahigh-speed optoelectronic technologies—is demonstrated in graphene through a nonlinear process that could potentially be generalized to other materials.
Abstract: Multiple optical harmonic generation—the multiplication of photon energy as a result of nonlinear interaction between light and matter—is a key technology in modern electronics and optoelectronics, because it allows the conversion of optical or electronic signals into signals with much higher frequency, and the generation of frequency combs. Owing to the unique electronic band structure of graphene, which features massless Dirac fermions1–3, it has been repeatedly predicted that optical harmonic generation in graphene should be particularly efficient at the technologically important terahertz frequencies4–6. However, these predictions have yet to be confirmed experimentally under technologically relevant operation conditions. Here we report the generation of terahertz harmonics up to the seventh order in single-layer graphene at room temperature and under ambient conditions, driven by terahertz fields of only tens of kilovolts per centimetre, and with field conversion efficiencies in excess of 10−3, 10−4 and 10−5 for the third, fifth and seventh terahertz harmonics, respectively. These conversion efficiencies are remarkably high, given that the electromagnetic interaction occurs in a single atomic layer. The key to such extremely efficient generation of terahertz high harmonics in graphene is the collective thermal response of its background Dirac electrons to the driving terahertz fields. The terahertz harmonics, generated via hot Dirac fermion dynamics, were observed directly in the time domain as electromagnetic field oscillations at these newly synthesized higher frequencies. The effective nonlinear optical coefficients of graphene for the third, fifth and seventh harmonics exceed the respective nonlinear coefficients of typical solids by 7–18 orders of magnitude7–9. Our results provide a direct pathway to highly efficient terahertz frequency synthesis using the present generation of graphene electronics, which operate at much lower fundamental frequencies of only a few hundreds of gigahertz. Efficient terahertz harmonic generation—challenging but important for ultrahigh-speed optoelectronic technologies—is demonstrated in graphene through a nonlinear process that could potentially be generalized to other materials.
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TL;DR: The Eurolight study illuminates the worldwide neglect of a major public-health problem, and reveals the inadequacies of responses to it in countries throughout the world.
Abstract: If it were needed, more evidence of the disconcerting under-treatment of headache disorders has come from the Eurolight study [1]. The topic is not new. Twenty years ago, the International and American Headache Societies jointly voiced their dismay at the inadequacies of health care for headache [2]. In 2006, the European Headache Federation and World Headache Alliance described migraine as a “forgotten epidemic” [3]. Meanwhile, in 2003, the Global Campaign against Headache [4–6] engaged the World Health Organization (WHO) as partner in this cause [7], embarking on a worldwide action programme which began by assessing the magnitude of headache in the world [4, 8]. In 2011, WHO’s global survey of headache disorders and resources, a Global Campaign project, laid bare the scale and scope of under-treated headache everywhere, and its consequences [9]. WHO wrote, in a message sent inter alia to the world’s Ministries of Health: “This first global enquiry into these matters illuminates the worldwide neglect of a major public-health problem, and reveals the inadequacies of responses to it in countries throughout the world” [9]. No words could be clearer but, to make sure, WHO repeated the message soon after [10]. Eurolight was a cross-sectional survey of over 8000 participants, conducted by multiple partners (scientific and lay) in 10 European countries [11]. A considerable strength of this study, apart from its size and geographical scope, was the use in all countries of the same questionnaire [12], a derivative of the HARDSHIP questionnaire already employed in many different countries, cultures and translations [13]. Also a strength was its scope of
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University of Mississippi Medical Center1, Veterans Health Administration2, University of Louisville3, University at Buffalo4, The Heart Research Institute5, Albert Einstein College of Medicine6, University of Würzburg7, Virginia Tech8, University of Virginia9, University of Southern California10, Huntington Medical Research Institutes11, Louisiana State University12, Harvard University13, National Institutes of Health14, University of California, Los Angeles15, Wayne State University16, Sant'Anna School of Advanced Studies17, Temple University18, University of California, Davis19, Cedars-Sinai Medical Center20, University of Duisburg-Essen21
TL;DR: The goal of this review is to provide best practice information regarding myocardial ischemia-reperfusion and infarction models and to provide increasing awareness of the need for rigor and reproducibility in designing and performing scientific research to ensure validation of results.
Abstract: Myocardial infarction is a prevalent major cardiovascular event that arises from myocardial ischemia with or without reperfusion, and basic and translational research is needed to better understand...
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TL;DR: Hans Erik Bøtker’s aim is to contribute towards the humanizing of cycling in Europe by inspiring and inspiring the next generation of cyclists and runners.
Abstract: The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment.
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TL;DR: A novel pathophysiological role is established for CMNLRP3 inflammasome signaling, with a mechanistic link to the pathogenesis of AF, and the inhibition of NLRP3 is established as a potential novel AF therapy approach.
Abstract: Background —Atrial fibrillation (AF) is frequently associated with enhanced inflammatory response. The "NACHT, LRR and PYD domain containing protein 3" (NLRP3)-inflammasome mediates caspase-1 activation and interleukin-1β release in immune cells, but is not known to play a role in cardiomyocytes (CMs). Here, we assessed the role of CM NLRP3-inflammasome in AF. Methods —NLRP3-inflammasome activation was assessed by immunoblot in atrial whole-tissue lysates and CMs from patients with paroxysmal (pAF) or long-standing persistent (chronic) AF (cAF). To determine whether CM-specific activation of NLPR3 is sufficient to promote AF, a CM-specific knock-in mouse model expressing constitutively active NLRP3 (CM-KI) was established. In vivo electrophysiology was used to assess atrial arrhythmia vulnerability. To evaluate the mechanism of AF, electrical activation pattern, Ca 2+ spark frequency (CaSF), atrial effective refractory period (AERP), and morphology of atria were evaluated in CM-KI mice and WT littermates. Results —NLRP3-inflammasome activity was increased in atrial CMs of pAF and cAF patients. CM-KI mice developed spontaneous premature atrial contractions and inducible AF, which was attenuated by a specific NLRP3-inflammasome inhibitor, MCC950. CM-KI mice exhibited ectopic activity, abnormal sarcoplasmic-reticulum Ca 2+ -release, AERP shortening and atrial hypertrophy. Adeno-associated virus subtype-9 mediated CM-specific knockdown of Nlrp3 suppressed AF development in CM-KI mice. Finally, genetic inhibition of Nlrp3 prevented AF development in CREM transgenic mice, a well-characterized mouse model of spontaneous AF. Conclusions —Our study establishes a novel pathophysiological role for CM NLRP3-inflammasome signaling with a mechanistic link to the pathogenesis of AF, and establishes inhibition of NLRP3 as a potential novel AF-therapy approach.
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University of Geneva1, University College Dublin2, Swiss Federal Institute of Aquatic Science and Technology3, Instituto Superior de Agronomia4, Institut national de la recherche agronomique5, University of Coimbra6, University of Milano-Bicocca7, Naturalis8, Queen Mary University of London9, University of Cantabria10, Trinity College, Dublin11, University of Salento12, International Sleep Products Association13, American Museum of Natural History14, Free University of Berlin15, University of Duisburg-Essen16, Swedish University of Agricultural Sciences17
TL;DR: The main advantages and pitfalls of metabarcoding approaches to assess parameters such as richness, abundance, taxonomic composition and species ecological values, to be used for calculation of biotic indices are discussed.
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TL;DR: An overview of some of the latest methodological developments in human ultra-high field MRI/MRS as well as associated clinical and scientific applications is presented, with emphasis on techniques that particularly benefit from the changing physical characteristics at high magnetic fields.
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TL;DR: Pretreatment ctDNA levels and molecular responses are independently prognostic of outcomes in aggressive lymphomas, and these risk factors could potentially guide future personalized risk-directed approaches.
Abstract: PurposeOutcomes for patients with diffuse large B-cell lymphoma remain heterogeneous, with existing methods failing to consistently predict treatment failure. We examined the additional prognostic value of circulating tumor DNA (ctDNA) before and during therapy for predicting patient outcomes.Patients and MethodsWe studied the dynamics of ctDNA from 217 patients treated at six centers, using a training and validation framework. We densely characterized early ctDNA dynamics during therapy using cancer personalized profiling by deep sequencing to define response-associated thresholds within a discovery set. These thresholds were assessed in two independent validation sets. Finally, we assessed the prognostic value of ctDNA in the context of established risk factors, including the International Prognostic Index and interim positron emission tomography/computed tomography scans.ResultsBefore therapy, ctDNA was detectable in 98% of patients; pretreatment levels were prognostic in both front-line and salvage se...
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TL;DR: This study presents the first systematic review of the state-of-the-art research on classifying skin lesions with CNNs, and discusses why the comparability of the presented procedures is very difficult and which challenges must be addressed in the future.
Abstract: Background: State-of-the-art classifiers based on convolutional neural networks (CNNs) were shown to classify images of skin cancer on par with dermatologists and could enable lifesaving and fast diagnoses, even outside the hospital via installation of apps on mobile devices. To our knowledge, at present there is no review of the current work in this research area. Objective: This study presents the first systematic review of the state-of-the-art research on classifying skin lesions with CNNs. We limit our review to skin lesion classifiers. In particular, methods that apply a CNN only for segmentation or for the classification of dermoscopic patterns are not considered here. Furthermore, this study discusses why the comparability of the presented procedures is very difficult and which challenges must be addressed in the future. Methods: We searched the Google Scholar, PubMed, Medline, ScienceDirect, and Web of Science databases for systematic reviews and original research articles published in English. Only papers that reported sufficient scientific proceedings are included in this review. Results: We found 13 papers that classified skin lesions using CNNs. In principle, classification methods can be differentiated according to three principles. Approaches that use a CNN already trained by means of another large dataset and then optimize its parameters to the classification of skin lesions are the most common ones used and they display the best performance with the currently available limited datasets. Conclusions: CNNs display a high performance as state-of-the-art skin lesion classifiers. Unfortunately, it is difficult to compare different classification methods because some approaches use nonpublic datasets for training and/or testing, thereby making reproducibility difficult. Future publications should use publicly available benchmarks and fully disclose methods used for training to allow comparability.
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Leiden University1, University of Maryland, Baltimore2, Beth Israel Deaconess Medical Center3, National Research Council4, University of Turin5, University of Duisburg-Essen6, University of Hamburg7, University of New South Wales8, Stanford University9, University of Basel10, University of Toledo11, University of Oxford12, Karolinska Institutet13, McGill University14, University of Marburg15, Aarhus University16, University of Colorado Boulder17, University of Wisconsin-Madison18
TL;DR: This paper forms a first step towards developing evidence-based and ethical recommendations about the implications of placebo and nocebo research for medical practice, based on the current state of evidence and the consensus of experts.
Abstract: Background: Placebo and nocebo effects occur in clinical or laboratory medical contexts after administration of an inert treatment or as part of active treatments and are due to psychobiological mechanisms such as expectancies of the patient. Placebo and nocebo studies have evolved from predominantly methodological research into a far-reaching interdisciplinary field that is unravelling the neurobiological, behavioural and clinical underpinnings of these phenomena in a broad variety of medical conditions. As a consequence, there is an increasing demand from health professionals to develop expert recommendations about evidence-based and ethical use of placebo and nocebo effects for clinical practice. Methods: A survey and interdisciplinary expert meeting by invitation was organized as part of the 1st Society for Interdisciplinary Placebo Studies (SIPS) conference in 2017. Twenty-nine internationally recognized placebo researchers participated. Results: There was consensus that maximizing placebo effects and minimizing nocebo effects should lead to better treatment outcomes with fewer side effects. Experts particularly agreed on the importance of informing patients about placebo and nocebo effects and training health professionals in patient-clinician communication to maximize placebo and minimize nocebo effects. Conclusions: The current paper forms a first step towards developing evidence-based and ethical recommendations about the implications of placebo and nocebo research for medical practice, based on the current state of evidence and the consensus of experts. Future research might focus on how to implement these recommendations, including how to optimize conditions for educating patients about placebo and nocebo effects and providing training for the implementation in clinical practice.
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TL;DR: The observed photoelectrochemical activity of the 2D-COF films and their photocorrosion stability in water pave the way for a novel class of photoabsorber materials with versatile optical and electronic properties that are tunable through the selection of appropriate building blocks and their three-dimensional stacking.
Abstract: Light-driven water electrolysis at a semiconductor surface is a promising way to generate hydrogen from sustainable energy sources, but its efficiency is limited by the performance of available photoabsorbers. Here we report the first time investigation of covalent organic frameworks (COFs) as a new class of photoelectrodes. The presented 2D-COF structure is assembled from aromatic amine-functionalized tetraphenylethylene and thiophene-based dialdehyde building blocks to form conjugated polyimine sheets, which π-stack in the third dimension to create photoactive porous frameworks. Highly oriented COF films absorb light in the visible range to generate photoexcited electrons that diffuse to the surface and are transferred to the electrolyte, resulting in proton reduction and hydrogen evolution. The observed photoelectrochemical activity of the 2D-COF films and their photocorrosion stability in water pave the way for a novel class of photoabsorber materials with versatile optical and electronic properties that are tunable through the selection of appropriate building blocks and their three-dimensional stacking.
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TL;DR: The voltage loss, determined by the difference between the optical gap (E-g) and the open-circuit voltage (V-OC), is one of the most important parameters determining the performance of organic sola.
Abstract: The voltage loss, determined by the difference between the optical gap (E-g) and the open-circuit voltage (V-OC), is one of the most important parameters determining the performance of organic sola ...
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TL;DR: A unique connection between MAS risk and chronic IL-18 is described, epithelial inflammasome hyperactivity is identified as a potential source, and the pathogenicity of free IL-16 is demonstrated, suggesting an IL- 18-driven pathway, complementary to the cytotoxic impairment of fHLH, with potential as a distinguishing biomarker and therapeutic target in MAS.
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Harvard University1, Novartis2, Autonomous University of Barcelona3, University of Texas MD Anderson Cancer Center4, Netherlands Cancer Institute5, Vanderbilt University6, National Institute for Health Research7, University of Duisburg-Essen8, University of California, San Francisco9, Memorial Sloan Kettering Cancer Center10
TL;DR: Alpelisib demonstrated a tolerable safety profile and encouraging preliminary activity in patients with PIK3CA-altered solid tumors, supporting the rationale for selective PI3Kα inhibition in combination with other agents for the treatment of PIK 3CA-mutant tumors.
Abstract: PurposeWe report the first-in-human phase Ia study to our knowledge (ClinicalTrialsgov identifier: NCT01219699) identifying the maximum tolerated dose and assessing safety and preliminary efficacy of single-agent alpelisib (BYL719), an oral phosphatidylinositol 3-kinase α (PI3Kα)–selective inhibitorPatients and MethodsIn the dose-escalation phase, patients with PIK3CA-altered advanced solid tumors received once-daily or twice-daily oral alpelisib on a continuous schedule In the dose-expansion phase, patients with PIK3CA-altered solid tumors and PIK3CA-wild-type, estrogen receptor–positive/human epidermal growth factor receptor 2–negative breast cancer received alpelisib 400 mg once dailyResultsOne hundred thirty-four patients received treatment Alpelisib maximum tolerated doses were established as 400 mg once daily and 150 mg twice daily Nine patients (132%) in the dose-escalation phase had dose-limiting toxicities of hyperglycemia (n = 6), nausea (n = 2), and both hyperglycemia and hypophosphatemi
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University of Tübingen1, Vanderbilt University2, Mayo Clinic3, Wolfson Medical Center4, University of Verona5, University of Parma6, Université libre de Bruxelles7, University of Cambridge8, Marche Polytechnic University9, Heidelberg University10, University of Duisburg-Essen11, Johns Hopkins University School of Medicine12, University of California, San Francisco13, National Institute for Health Research14, University of Amsterdam15, Aarhus University16
TL;DR: This expert statement proposed during the third international conference on “Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease” formulates evidence- and expert-based suggestions on the indications, contraindications, patient selection, and procedural aspects of the procedure.
Abstract: Transbronchial cryobiopsies (TBCB) have recently been introduced as a promising and safer alternative to surgical lung biopsy in the diagnostic approach to diffuse parenchymal lung diseases (DPLD). Despite a substantial and expanding body of literature, the technique has not yet been standardized and its place in the diagnostic algorithm of DPLD remains to be defined. In part, this reflects concerns over the diagnostic yield and safety of the procedure, together with the rapid spread of the technique without competency and safety standards; furthermore, there is a substantial procedural variability among centers and interventional pulmonologists. We report this expert statement proposed during the third international conference on "Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease" (Ravenna, October 27-28, 2016), which formulates evidence- and expert-based suggestions on the indications, contraindications, patient selection, and procedural aspects of the procedure. The following 5 domains were reviewed: (1) what is the role of TBCB in the diagnostic evaluation of DPLD: patient selection; (2) pathological considerations; (3) contraindications and safety considerations; (4) how should TBCB be performed and in what procedural environment; and (5) who should perform TBCB. Finally, the existence of white paper recommendations may also reassure local hospital credentialing committees tasked with endorsing an adoption of the technique.