Showing papers by "University of Bologna published in 2018"
Gregory A. Roth1, Gregory A. Roth2, Degu Abate3, Kalkidan Hassen Abate4 +1025 more•Institutions (333)
TL;DR: Non-communicable diseases comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2).
5,211 citations
Kindai University1, University of California, Los Angeles2, Yonsei University3, University of Bologna4, California Pacific Medical Center5, Fourth Military Medical University6, Gdańsk Medical University7, University of Bordeaux8, Hannover Medical School9, Beatson West of Scotland Cancer Centre10, Eisai11, National Taiwan University12
TL;DR: Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma and the safety and tolerability profiles of lenvatinIB were consistent with those previously observed.
3,046 citations
Jeffrey D. Stanaway1, Ashkan Afshin1, Emmanuela Gakidou1, Stephen S Lim1 +1050 more•Institutions (346)
TL;DR: This study estimated levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs) by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017 and explored the relationship between development and risk exposure.
2,910 citations
TL;DR: This annotated reference sequence of wheat is a resource that can now drive disruptive innovation in wheat improvement, as this community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding.
Abstract: An annotated reference sequence representing the hexaploid bread wheat genome in 21 pseudomolecules has been analyzed to identify the distribution and genomic context of coding and noncoding elements across the A, B, and D subgenomes. With an estimated coverage of 94% of the genome and containing 107,891 high-confidence gene models, this assembly enabled the discovery of tissue- and developmental stage-related coexpression networks by providing a transcriptome atlas representing major stages of wheat development. Dynamics of complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. This community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding.
2,118 citations
Columbia University1, University of Amsterdam2, University of Bologna3, University of Mainz4, University of Münster5, University of Coimbra6, New York University Abu Dhabi7, University of Zurich8, Stockholm University9, Rensselaer Polytechnic Institute10, Max Planck Society11, Weizmann Institute of Science12, University of Freiburg13, University of Nantes14, University of California, San Diego15, University of Chicago16, Purdue University17, Rice University18, Pierre-and-Marie-Curie University19, University of California, Los Angeles20
TL;DR: In this article, a search for weakly interacting massive particles (WIMPs) using 278.8 days of data collected with the XENON1T experiment at LNGS is reported.
Abstract: We report on a search for weakly interacting massive particles (WIMPs) using 278.8 days of data collected with the XENON1T experiment at LNGS. XENON1T utilizes a liquid xenon time projection chamber with a fiducial mass of (1.30±0.01) ton, resulting in a 1.0 ton yr exposure. The energy region of interest, [1.4,10.6] keVee ([4.9,40.9] keVnr), exhibits an ultralow electron recoil background rate of [82-3+5(syst)±3(stat)] events/(ton yr keVee). No significant excess over background is found, and a profile likelihood analysis parametrized in spatial and energy dimensions excludes new parameter space for the WIMP-nucleon spin-independent elastic scatter cross section for WIMP masses above 6 GeV/c2, with a minimum of 4.1×10-47 cm2 at 30 GeV/c2 and a 90% confidence level.
1,808 citations
Memorial Sloan Kettering Cancer Center1, University College London2, National Taiwan University3, University of Southern California4, University of Ulsan5, Trakya University6, University of Bordeaux7, University of Bologna8, University of Amsterdam9, The Chinese University of Hong Kong10, University of California, San Francisco11
TL;DR: Treatment with cabozantinib resulted in longer overall survival and progression‐free survival than placebo among patients with previously treated advanced hepatocellular carcinoma, and the rate of high‐grade adverse events in the cabozaninib group was approximately twice that observed in the placebo group.
Abstract: Background Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellul...
1,471 citations
TL;DR: Whether therapies to modulate inflammageing can reduce the age-related decline in health is discussed, and the hypothesis that inflammation affects CVD, multimorbidity, and frailty is supported by mechanistic studies but requires confirmation in humans.
Abstract: Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty — which affect clinical manifestations, prognosis, and response to treatment — and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials. Inflammageing is a chronic, pro-inflammatory state that develops with age and is a risk factor for cardiovascular disease, comorbidities, frailty, and death. In this Review, Ferrucci and Fabbri discuss whether therapies to modulate inflammageing can reduce the age-related decline in health.
1,428 citations
TL;DR: It is argued that chronic diseases are not only the result of ageing and inflammaging; these diseases also accelerate the ageing process and can be considered a manifestation of accelerated ageing, and the use of new biomarkers capable of assessing biological versus chronological age in metabolic diseases is proposed.
Abstract: Ageing and age-related diseases share some basic mechanistic pillars that largely converge on inflammation. During ageing, chronic, sterile, low-grade inflammation - called inflammaging - develops, which contributes to the pathogenesis of age-related diseases. From an evolutionary perspective, a variety of stimuli sustain inflammaging, including pathogens (non-self), endogenous cell debris and misplaced molecules (self) and nutrients and gut microbiota (quasi-self). A limited number of receptors, whose degeneracy allows them to recognize many signals and to activate the innate immune responses, sense these stimuli. In this situation, metaflammation (the metabolic inflammation accompanying metabolic diseases) is thought to be the form of chronic inflammation that is driven by nutrient excess or overnutrition; metaflammation is characterized by the same mechanisms underpinning inflammaging. The gut microbiota has a central role in both metaflammation and inflammaging owing to its ability to release inflammatory products, contribute to circadian rhythms and crosstalk with other organs and systems. We argue that chronic diseases are not only the result of ageing and inflammaging; these diseases also accelerate the ageing process and can be considered a manifestation of accelerated ageing. Finally, we propose the use of new biomarkers (DNA methylation, glycomics, metabolomics and lipidomics) that are capable of assessing biological versus chronological age in metabolic diseases.
1,380 citations
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
Columbia University1, St Bartholomew's Hospital2, University of Bologna3, Federal University of Rio de Janeiro4, Heidelberg University5, Mayo Clinic6, Stanford University7, French Institute of Health and Medical Research8, University of Pennsylvania9, Northwestern University10, Cleveland Clinic11, Medical University of South Carolina12, Pfizer13
TL;DR: In patients with transthyretin amyloid cardiomyopathy, tafamidis was associated with reductions in all‐cause mortality and cardiovascular‐related hospitalizations and reduced the decline in functional capacity and quality of life as compared with placebo.
Abstract: Background Transthyretin amyloid cardiomyopathy is caused by the deposition of transthyretin amyloid fibrils in the myocardium. The deposition occurs when wild-type or variant transthyretin becomes unstable and misfolds. Tafamidis binds to transthyretin, preventing tetramer dissociation and amyloidogenesis. Methods In a multicenter, international, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 441 patients with transthyretin amyloid cardiomyopathy in a 2:1:2 ratio to receive 80 mg of tafamidis, 20 mg of tafamidis, or placebo for 30 months. In the primary analysis, we hierarchically assessed all-cause mortality, followed by frequency of cardiovascular-related hospitalizations according to the Finkelstein–Schoenfeld method. Key secondary end points were the change from baseline to month 30 for the 6-minute walk test and the score on the Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS), in which higher scores indicate better health status. Results In the prim...
1,340 citations
University of Milan1, Instituto Português de Oncologia Francisco Gentil2, Curie Institute3, Leiden University Medical Center4, Vienna General Hospital5, University College London6, Leiden University7, Institut Jules Bordet8, Netherlands Cancer Institute9, Turku University Hospital10, University of Oxford11, University of Mannheim12, Ludwig Maximilian University of Munich13, Helsinki University Central Hospital14, The Royal Marsden NHS Foundation Trust15, Institute of Cancer Research16, University Medical Center Groningen17, Radboud University Nijmegen18, Institut Gustave Roussy19, Tel Aviv Sourasky Medical Center20, University Hospital of Lausanne21, University of Bologna22, University of Turin23, Weston Park Hospital24, Aarhus University Hospital25, Katholieke Universiteit Leuven26, Erasmus University Rotterdam27, Oslo University Hospital28, University College Hospital29, Claude Bernard University Lyon 130
TL;DR: The fundamental pathogenic mechanisms underlying implant infections are explored, highlighting orthopaedic implants and Staphylococcus aureus as a prime example, and innovative targets for preventive and therapeutic strategies are discussed.
Abstract: Medical device-associated infections account for a large proportion of hospital-acquired infections. A variety of opportunistic pathogens can cause implant infections, depending on the type of the implant and on the anatomical site of implantation. The success of these versatile pathogens depends on rapid adhesion to virtually all biomaterial surfaces and survival in the hostile host environment. Biofilm formation on implant surfaces shelters the bacteria and encourages persistence of infection. Furthermore, implant-infecting bacteria can elude innate and adaptive host defences as well as biocides and antibiotic chemotherapies. In this Review, we explore the fundamental pathogenic mechanisms underlying implant infections, highlighting orthopaedic implants and Staphylococcus aureus as a prime example, and discuss innovative targets for preventive and therapeutic strategies.
Hacettepe University1, Boston Children's Hospital2, Katholieke Universiteit Leuven3, University of Bologna4, Radboud University Nijmegen5, University of Aberdeen6, Claude Bernard University Lyon 17, European Respiratory Society8, Cardiff University9, University Hospital of Lausanne10, University of Queensland11, Ghent University12, University of Paris13, Istituto Giannina Gaslini14, Post Graduate Institute of Medical Education and Research15, Carlos III Health Institute16, National and Kapodistrian University of Athens17, University of Rennes18, University Hospital Heidelberg19, University College London20, Goethe University Frankfurt21, Catholic University of the Sacred Heart22, McGill University23
TL;DR: Treatment duration for aspergillosis is strongly recommended based on clinical improvement, degree of immunosuppression and response on imaging, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended.
TL;DR: Recent cumulative data suggest that, without the existence of the immunosenescence/inflamm-aging duo, human longevity would be greatly shortened and it may be more suitable to aim to maintain general homeostasis and function by appropriately improving immune-inflammatory-functions.
Abstract: The immune system is the most important protective physiological system of the organism. It has many connections with other systems and is, in fact, often considered as part of the larger neuro-endocrine-immune axis. Most experimental data on immune changes with aging show a decline in many immune parameters when compared to young healthy subjects. The bulk of these changes is termed immunosenescence. Immunosenescence has been considered for some time as detrimental because it often leads to subclinical accumulation of pro-inflammatory factors and inflamm-aging. Together, immunosenescence and inflamm-aging are suggested to stand at the origin of most of the diseases of the elderly, such as infections, cancer, autoimmune disorders, and chronic inflammatory diseases. However, an increasing number of immune-gerontologists have challenged this negative interpretation of immunosenescence with respect to its significance in aging-related alterations of the immune system. If one considers these changes from an evolutionary perspective, they can be viewed preferably as adaptive or remodeling rather than solely detrimental. Whereas it is conceivable that global immune changes may lead to various diseases, it is also obvious that these changes may be needed for extended survival/longevity. Recent cumulative data suggest that, without the existence of the immunosenescence/inflamm-aging duo (representing two sides of the same phenomenon), human longevity would be greatly shortened. This review summarizes recent data on the dynamic reassessment of immune changes with aging. Accordingly, attempts to intervene on the aging immune system by targeting its rejuvenation, it may be more suitable to aim to maintain general homeostasis and function by appropriately improving immune-inflammatory-functions.
Catholic University of the Sacred Heart1, Memorial Sloan Kettering Cancer Center2, International Agency for Research on Cancer3, University Health Network4, University of Lausanne5, Centre Hospitalier Universitaire de Grenoble6, Utrecht University7, Charité8, University of Texas MD Anderson Cancer Center9, Technische Universität München10, Belfast Health and Social Care Trust11, University of Zurich12, University of Nottingham13, Beatson West of Scotland Cancer Centre14, Tohoku University15, University of Verona16, Institut Gustave Roussy17, University of Bologna18, Radboud University Nijmegen19
TL;DR: This work believes this conceptual approach can form the basis for the next generation of NEN classifications and will allow more consistent taxonomy to understand how neoplasms from different organ systems inter-relate clinically and genetically.
TL;DR: The International Registry of Acute Aortic Dissection (IRAD) was established in 1996 with the mission to raise awareness of this condition and provide insights to guide diagnosis and treatment as mentioned in this paper.
Abstract: Acute aortic dissection (AAD) is a life-threatening condition associated with high morbidity and mortality rates, and it remains a challenge to diagnose and treat. The International Registry of Acute Aortic Dissection was established in 1996 with the mission to raise awareness of this condition and provide insights to guide diagnosis and treatment. Since then, >7300 cases have been included from >51 sites in 12 countries. Although presenting symptoms and physical findings have not changed significantly over this period, the use of computed tomography in the diagnosis has increased, and more patients are managed with interventional procedures: surgery in type A AAD and endovascular therapy in type B AAD; with these changes in care, there has been a significant decrease in overall in-hospital mortality in type A AAD but not in type B AAD. Herein, we summarized the key lessons learned from this international registry of patients with AAD over the past 20 years.
King's College London1, Policlinico Umberto I2, Zhengzhou University3, University of Bergen4, University of Medicine and Pharmacy of Craiova5, University of Trieste6, University of Pavia7, Ludwig Maximilian University of Munich8, Imperial College London9, University of Verona10, Sapienza University of Rome11, Derriford Hospital12, University Hospital Regensburg13, University of Innsbruck14, Université Paris-Saclay15, University of Barcelona16, University of Copenhagen17, University of Bologna18, University of Virginia19, University of Vienna20, Eindhoven University of Technology21
TL;DR: The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications.
Abstract: The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications.
TL;DR: In this paper, the authors describe the processing of the Gaia DR2 data, and describe the criteria used to select the sample published in Gaia DR 2, and explore the data set to assess its quality.
Abstract: Context. The Gaia spacecraft of the European Space Agency (ESA) has been securing observations of solar system objects (SSOs) since the beginning of its operations. Data Release 2 (DR2) contains the observations of a selected sample of 14,099 SSOs. These asteroids have been already identified and have been numbered by the Minor Planet Center repository. Positions are provided for each Gaia observation at CCD level. As additional information, complementary to astrometry, the apparent brightness of SSOs in the unfiltered G band is also provided for selected observations.Aims. We explain the processing of SSO data, and describe the criteria we used to select the sample published in Gaia DR2. We then explore the data set to assess its quality.Methods. To exploit the main data product for the solar system in Gaia DR2, which is the epoch astrometry of asteroids, it is necessary to take into account the unusual properties of the uncertainty, as the position information is nearly one-dimensional. When this aspect is handled appropriately, an orbit fit can be obtained with post-fit residuals that are overall consistent with the a-priori error model that was used to define individual values of the astrometric uncertainty. The role of both random and systematic errors is described. The distribution of residuals allowed us to identify possible contaminants in the data set (such as stars). Photometry in the G band was compared to computed values from reference asteroid shapes and to the flux registered at the corresponding epochs by the red and blue photometers (RP and BP).Results. The overall astrometric performance is close to the expectations, with an optimal range of brightness G ~ 12 − 17. In this range, the typical transit-level accuracy is well below 1 mas. For fainter asteroids, the growing photon noise deteriorates the performance. Asteroids brighter than G ~ 12 are affected by a lower performance of the processing of their signals. The dramatic improvement brought by Gaia DR2 astrometry of SSOs is demonstrated by comparisons to the archive data and by preliminary tests on the detection of subtle non-gravitational effects.
TL;DR: In this paper, the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way is demonstrated. But the accuracy of the errors, statistical and systematic, are relatively well understood.
Abstract: Context. Aims: The goal of this paper is to demonstrate the outstanding quality of the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way. We focus here on determining the proper motions of 75 Galactic globular clusters, nine dwarf spheroidal galaxies, one ultra-faint system, and the Large and Small Magellanic Clouds. Methods: Using data extracted from the Gaia archive, we derived the proper motions and parallaxes for these systems, as well as their uncertainties. We demonstrate that the errors, statistical and systematic, are relatively well understood. We integrated the orbits of these objects in three different Galactic potentials, and characterised their properties. We present the derived proper motions, space velocities, and characteristic orbital parameters in various tables to facilitate their use by the astronomical community. Results: Our limited and straightforward analyses have allowed us for example to (i) determine absolute and very precise proper motions for globular clusters; (ii) detect clear rotation signatures in the proper motions of at least five globular clusters; (iii) show that the satellites of the Milky Way are all on high-inclination orbits, but that they do not share a single plane of motion; (iv) derive a lower limit for the mass of the Milky Way of 9.1-2.6+6.2 × 1011 M⊙ based on the assumption that the Leo I dwarf spheroidal is bound; (v) derive a rotation curve for the Large Magellanic Cloud based solely on proper motions that is competitive with line-of-sight velocity curves, now using many orders of magnitude more sources; and (vi) unveil the dynamical effect of the bar on the motions of stars in the Large Magellanic Cloud. Conclusions: All these results highlight the incredible power of the Gaia astrometric mission, and in particular of its second data release.
TL;DR: The major issues regarding this multi-step process, focussing in particular on challenges of the extraction of radiomic features from data sets provided by computed tomography, positron emission tomographic, and magnetic resonance imaging are summarised.
Abstract: Radiomics is an emerging translational field of research aiming to extract mineable high-dimensional data from clinical images. The radiomic process can be divided into distinct steps with definable inputs and outputs, such as image acquisition and reconstruction, image segmentation, features extraction and qualification, analysis, and model building. Each step needs careful evaluation for the construction of robust and reliable models to be transferred into clinical practice for the purposes of prognosis, non-invasive disease tracking, and evaluation of disease response to treatment. After the definition of texture parameters (shape features; first-, second-, and higher-order features), we briefly discuss the origin of the term radiomics and the methods for selecting the parameters useful for a radiomic approach, including cluster analysis, principal component analysis, random forest, neural network, linear/logistic regression, and other. Reproducibility and clinical value of parameters should be firstly tested with internal cross-validation and then validated on independent external cohorts. This article summarises the major issues regarding this multi-step process, focussing in particular on challenges of the extraction of radiomic features from data sets provided by computed tomography, positron emission tomography, and magnetic resonance imaging.
TL;DR: For the first time, specific loci that distinguish between BD and SCZ are discovered and polygenic components underlying multiple symptom dimensions are identified that point to the utility of genetics to inform symptomology and potential treatment.
University of Bern1, Institute of Cancer Research2, Oregon Health & Science University3, Cornell University4, Princess Margaret Cancer Centre5, Yonsei University6, University of Salford7, University of Copenhagen8, Monash University9, University of São Paulo10, Columbia University11, The Royal Marsden NHS Foundation Trust12, University of Texas MD Anderson Cancer Center13, University of California, Davis14, University of Bologna15, University of California, San Francisco16, University of Paris-Sud17, University of British Columbia18, Duke University19, University of Cologne20, Fred Hutchinson Cancer Research Center21, University of Birmingham22, Memorial Sloan Kettering Cancer Center23, University of Tampere24, American University of Beirut25, Medical University of Vienna26, Vanderbilt University27, Tata Memorial Hospital28, Icahn School of Medicine at Mount Sinai29, Ghent University30, University of Washington31, Université de Montréal32, Tulane University33, Tel Aviv University34, Harvard University35, Prostate Cancer Foundation36, Toho University37, University College London38, University of Toronto39, Université catholique de Louvain40, University of Milan41, University of Ulm42
TL;DR: The presented expert voting results can be used for support in areas of management of men with APC where there is no high-level evidence, but individualised treatment decisions should as always be based on all of the data available.
University of Brescia1, Karolinska Institutet2, University of Zagreb3, Athens State University4, Papworth Hospital5, Utrecht University6, Shaare Zedek Medical Center7, Medical University of Vienna8, Ege University9, University of Bologna10, Heidelberg University11, Poznan University of Medical Sciences12, University of Cambridge13, University of Zurich14
TL;DR: There is an urgent need to develop evidence‐based treatment algorithms to prolong life when possible and in accordance with patient preferences, increase life quality, and reduce the burden of hospitalization in this vulnerable patient population.
Abstract: This article updates the Heart Failure Association of the European Society of Cardiology (ESC) 2007 classification of advanced heart failure and describes new diagnostic and treatment options for these patients. Recognizing the patient with advanced heart failure is critical to facilitate timely referral to advanced heart failure centres. Unplanned visits for heart failure decompensation, malignant arrhythmias, co-morbidities, and the 2016 ESC guidelines criteria for the diagnosis of heart failure with preserved ejection fraction are included in this updated definition. Standard treatment is, by definition, insufficient in these patients. Inotropic therapy may be used as a bridge strategy, but it is only a palliative measure when used on its own, because of the lack of outcomes data. Major progress has occurred with short-term mechanical circulatory support devices for immediate management of cardiogenic shock and long-term mechanical circulatory support for either a bridge to transplantation or as destination therapy. Heart transplantation remains the treatment of choice for patients without contraindications. Some patients will not be candidates for advanced heart failure therapies. For these patients, who are often elderly with multiple co-morbidities, management of advanced heart failure to reduce symptoms and improve quality of life should be emphasized. Robust evidence from prospective studies is lacking for most therapies for advanced heart failure. There is an urgent need to develop evidence-based treatment algorithms to prolong life when possible and in accordance with patient preferences, increase life quality, and reduce the burden of hospitalization in this vulnerable patient population.
TL;DR: The authors provide an overview of the current state of the literature on the relationship between social media; political polarization; and political "disinformation", a term used to encompass a wide range of types of information about politics found online.
Abstract: The following report is intended to provide an overview of the current state of the literature on the relationship between social media; political polarization; and political “disinformation,” a term used to encompass a wide range of types of information about politics found online, including “fake news,” rumors, deliberately factually incorrect information, inadvertently factually incorrect information, politically slanted information, and “hyperpartisan” news. The review of the literature is provided in six separate sections, each of which can be read individually but that cumulatively are intended to provide an overview of what is known — and unknown — about the relationship between social media, political polarization, and disinformation. The report concludes by identifying key gaps in our understanding of these phenomena and the data that are needed to address them.
TL;DR: The hypothesis that ARDs and GSs such as frailty can be conceptualized as accelerated aging will be discussed, and the use of DNA methylation, N-glycans profiling, and gut microbiota composition to complement the available disease-specific markers are proposed.
Abstract: Geroscience, the new interdisciplinary field that aims to understand the relationship between aging and chronic age-related diseases (ARDs) and geriatric syndromes (GSs), is based on epidemiological evidence and experimental data that aging is the major risk factor for such pathologies and assumes that aging and ARDs/GSs share a common set of basic biological mechanisms. A consequence is that the primary target of medicine is to combat aging instead of any single ARD/GSs one by one, as favored by the fragmentation into hundreds of specialties and sub-specialties. If the same molecular and cellular mechanisms underpin both aging and ARDs/GSs, a major question emerges: which is the difference, if any, between aging and ARDs/GSs? The hypothesis that ARDs and GSs such as frailty can be conceptualized as accelerated aging will be discussed by analyzing in particular frailty, sarcopenia, chronic obstructive pulmonary disease, cancer, neurodegenerative diseases such as Alzheimer and Parkinson as well as Down syndrome as an example of progeroid syndrome. According to this integrated view, aging and ARDs/GSs become part of a continuum where precise boundaries do not exist and the two extremes are represented by centenarians, who largely avoided or postponed most ARDs/GSs and are characterized by decelerated aging, and patients who suffered one or more severe ARDs in their sixties, seventies and eighties and show signs of accelerated aging, respectively. In between these two extremes there is a continuum of intermediate trajectories representing a sort of grey area. Thus, clinically different, classically-defined ARDs/GSs are indeed the result of peculiar combinations of alterations regarding the same, limited set of basic mechanisms shared with the aging process. Whether an individual will follow a trajectory of accelerated or decelerated aging will depend on his/her genetic background interacting lifelong with environmental and lifestyle factors. If ARDs and GSs are manifestations of accelerated aging, it is urgent to identify markers capable of distinguishing between biological and chronological age in order to identify subjects at higher risk of developing ARDs and GSs. To this aim we propose the use of DNA methylation, N-glycans profiling and gut microbiota composition to complement the available disease-specific markers.
Harvard University1, University of Cologne2, Memorial Sloan Kettering Cancer Center3, University of Texas MD Anderson Cancer Center4, University of Bologna5, University of California, Los Angeles6, University of Oxford7, Wayne State University8, Emory University9, University of Toronto10, University of British Columbia11, Charles University in Prague12, Bristol-Myers Squibb13
TL;DR: With extended follow-up, responses to nivolumab were frequent and durable and seems to be associated with a favorable safety profile and long-term benefits across a broad spectrum of patients with relapsed/refractory cHL.
Abstract: PurposeGenetic alterations causing overexpression of programmed death-1 ligands are near universal in classic Hodgkin lymphoma (cHL). Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated efficacy in relapsed/refractory cHL after autologous hematopoietic cell transplantation (auto-HCT) in initial analyses of one of three cohorts from the CheckMate 205 study of nivolumab for cHL. Here, we assess safety and efficacy after extended follow-up of all three cohorts.MethodsThis multicenter, single-arm, phase II study enrolled patients with relapsed/refractory cHL after auto-HCT treatment failure into cohorts by treatment history: brentuximab vedotin (BV)–naive (cohort A), BV received after auto-HCT (cohort B), and BV received before and/or after auto-HCT (cohort C). All patients received nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary end point was objective response rate per independent radiology review committee.ResultsOverall, 243 patients were treated...
TL;DR: In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented.
Abstract: Many measurements and searches for physics beyond the standard model at the LHC rely on the efficient identification of heavy-flavour jets, i.e. jets originating from bottom or charm quarks. In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented. Heavy-flavour jet identification algorithms have been improved compared to those used previously at centre-of-mass energies of 7 and 8 TeV. For jets with transverse momenta in the range expected in simulated events, these new developments result in an efficiency of 68% for the correct identification of a b jet for a probability of 1% of misidentifying a light-flavour jet. The improvement in relative efficiency at this misidentification probability is about 15%, compared to previous CMS algorithms. In addition, for the first time algorithms have been developed to identify jets containing two b hadrons in Lorentz-boosted event topologies, as well as to tag c jets. The large data sample recorded in 2016 at a centre-of-mass energy of 13 TeV has also allowed the development of new methods to measure the efficiency and misidentification probability of heavy-flavour jet identification algorithms. The b jet identification efficiency is measured with a precision of a few per cent at moderate jet transverse momenta (between 30 and 300 GeV) and about 5% at the highest jet transverse momenta (between 500 and 1000 GeV).
TL;DR: This Perspective will focus on the molecular and computational approaches that underpin drug design by medicinal chemists to promote understanding and collaboration with clinical scientists.
Abstract: Diseases of infection, of neurodegeneration (such as Alzheimer’s and Parkinson’s diseases), and of malignancy (cancers) have complex and varied causative factors. Modern drug discovery has the power to identify potential modulators for multiple targets from millions of compounds. Computational approaches allow the determination of the association of each compound with its target before chemical synthesis and biological testing is done. These approaches depend on the prior identification of clinically and biologically validated targets. This Perspective will focus on the molecular and computational approaches that underpin drug design by medicinal chemists to promote understanding and collaboration with clinical scientists.
University of Milan1, Instituto Português de Oncologia Francisco Gentil2, Paris Descartes University3, Leiden University Medical Center4, Vienna General Hospital5, University College London6, Lund University7, Leiden University8, Institut Jules Bordet9, Netherlands Cancer Institute10, Turku University Hospital11, University of Oxford12, Heidelberg University13, Ludwig Maximilian University of Munich14, Helsinki University Central Hospital15, The Royal Marsden NHS Foundation Trust16, Institute of Cancer Research17, University Medical Center Groningen18, Radboud University Nijmegen19, Institut Gustave Roussy20, Tel Aviv Sourasky Medical Center21, University Hospital of Lausanne22, University of Bologna23, University of Turin24, Weston Park Hospital25, Curie Institute26, Aarhus University27, Katholieke Universiteit Leuven28, Erasmus University Rotterdam29, Oslo University Hospital30, University College Hospital31, Claude Bernard University Lyon 132
TL;DR: Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy; Instituto Portugues de Oncologia de Lisboa Francisco Gentil, EPE, Lisbon, Portugal; University Hospital Essen, Essen Germany; Department of Oncological Orthopedics, Musculoskeletal Tissue Bank, IFO, Regina Elena National Cancer Institute, Rome, Italy.
TL;DR: This work observes self-bound droplets in free space, and characterize the conditions for their formation as well as their size and composition, which sets the stage for future studies on quantum droplets, from the measurement of their peculiar excitation spectrum to the exploration of their superfluid nature.
Abstract: Self-bound quantum droplets are a newly discovered phase in the context of ultracold atoms. In this Letter, we report their experimental realization following the original proposal by Petrov [Phys. Rev. Lett. 115, 155302 (2015)PRLTAO0031-900710.1103/PhysRevLett.115.155302], using an attractive bosonic mixture. In this system, spherical droplets form due to the balance of competing attractive and repulsive forces, provided by the mean-field energy close to the collapse threshold and the first-order correction due to quantum fluctuations. Thanks to an optical levitating potential with negligible residual confinement, we observe self-bound droplets in free space, and we characterize the conditions for their formation as well as their size and composition. This work sets the stage for future studies on quantum droplets, from the measurement of their peculiar excitation spectrum to the exploration of their superfluid nature.