scispace - formally typeset
Search or ask a question

Showing papers by "University of Florence published in 2020"


Journal ArticleDOI
TL;DR: During the COVID-19 outbreak, medical health workers had psychosocial problems and risk factors for developing them and were in need of attention and recovery programs.
Abstract: Objective: We explored whether medical health workers had more psychosocial problems than nonmedical health workers during the COVID-19 outbreak. Methods: An online survey was run from February 19 to March 6, 2020; a total of 2,182 Chinese subjects participated. Mental health variables were assessed via the Insomnia Severity Index (ISI), the Symptom Check List-revised (SCL-90-R), and the Patient Health Questionnaire-4 (PHQ-4), which included a 2-item anxiety scale and a 2-item depression scale (PHQ-2). Results: Compared with nonmedical health workers (n = 1,255), medical health workers (n = 927) had a higher prevalence of insomnia (38.4 vs. 30.5%, p < 0.01), anxiety (13.0 vs. 8.5%, p < 0.01), depression (12.2 vs. 9.5%; p< 0.04), somatization (1.6 vs. 0.4%; p < 0.01), and obsessive-compulsive symptoms (5.3 vs. 2.2%; p < 0.01). They also had higher total scores of ISI, GAD-2, PHQ-2, and SCL-90-R obsessive-compulsive symptoms (p ≤ 0.01). Among medical health workers, having organic disease was an independent factor for insomnia, anxiety, depression, somatization, and obsessive-compulsive symptoms (p < 0.05 or 0.01). Living in rural areas, being female, and being at risk of contact with COVID-19 patients were the most common risk factors for insomnia, anxiety, obsessive-compulsive symptoms, and depression (p < 0.01 or 0.05). Among nonmedical health workers, having organic disease was a risk factor for insomnia, depression, and obsessive-compulsive symptoms (p < 0.01 or 0.05). Conclusions: During the COVID-19 outbreak, medical health workers had psychosocial problems and risk factors for developing them. They were in need of attention and recovery programs.

1,056 citations


Journal ArticleDOI
TL;DR: This expert Consensus Statement, endorsed by the ENS-CCA, summarizes the latest advances in CCA, including classification, genetics and treatment, and provides recommendations for CCA management and priorities across basic, translational and clinical research.
Abstract: Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted

926 citations


Journal ArticleDOI
Joan B. Soriano1, Parkes J Kendrick2, Katherine R. Paulson2, Vinay Gupta2  +311 moreInstitutions (178)
TL;DR: It is shown that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.

829 citations


Journal ArticleDOI
TL;DR: This review begins by reviewing protocols of quantum key distribution based on discrete variable systems, and considers aspects of device independence, satellite challenges, and high rate protocols based on continuous variable systems.
Abstract: Quantum cryptography is arguably the fastest growing area in quantum information science. Novel theoretical protocols are designed on a regular basis, security proofs are constantly improving, and experiments are gradually moving from proof-of-principle lab demonstrations to in-field implementations and technological prototypes. In this paper, we provide both a general introduction and a state-of-the-art description of the recent advances in the field, both theoretical and experimental. We start by reviewing protocols of quantum key distribution based on discrete variable systems. Next we consider aspects of device independence, satellite challenges, and protocols based on continuous-variable systems. We will then discuss the ultimate limits of point-to-point private communications and how quantum repeaters and networks may overcome these restrictions. Finally, we will discuss some aspects of quantum cryptography beyond standard quantum key distribution, including quantum random number generators and quantum digital signatures.

769 citations


Journal ArticleDOI
TL;DR: In this article, the authors analyzed the temporal dynamics of the coronavirus disease 2019 outbreak in China, Italy and France in the time window 22 / 01 − 15 / 03 / 2020.
Abstract: In this note we analyze the temporal dynamics of the coronavirus disease 2019 outbreak in China, Italy and France in the time window 22 / 01 − 15 / 03 / 2020 . A first analysis of simple day-lag maps points to some universality in the epidemic spreading, suggesting that simple mean-field models can be meaningfully used to gather a quantitative picture of the epidemic spreading, and notably the height and time of the peak of confirmed infected individuals. The analysis of the same data within a simple susceptible-infected-recovered-deaths model indicates that the kinetic parameter that describes the rate of recovery seems to be the same, irrespective of the country, while the infection and death rates appear to be more variable. The model places the peak in Italy around March 21st 2020, with a peak number of infected individuals of about 26000 (not including recovered and dead) and a number of deaths at the end of the epidemics of about 18,000. Since the confirmed cases are believed to be between 10 and 20% of the real number of individuals who eventually get infected, the apparent mortality rate of COVID-19 falls between 4% and 8% in Italy, while it appears substantially lower, between 1% and 3% in China. Based on our calculations, we estimate that 2500 ventilation units should represent a fair figure for the peak requirement to be considered by health authorities in Italy for their strategic planning. Finally, a simulation of the effects of drastic containment measures on the outbreak in Italy indicates that a reduction of the infection rate indeed causes a quench of the epidemic peak. However, it is also seen that the infection rate needs to be cut down drastically and quickly to observe an appreciable decrease of the epidemic peak and mortality rate. This appears only possible through a concerted and disciplined, albeit painful, effort of the population as a whole.

720 citations


Journal ArticleDOI
TL;DR: 20 international experts including 19 members of the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer OligoCare project developed a comprehensive system for characterisation and classification of oligometastatic disease.
Abstract: Oligometastatic disease has been proposed as an intermediate state between localised and systemically metastasised disease. In the absence of randomised phase 3 trials, early clinical studies show improved survival when radical local therapy is added to standard systemic therapy for oligometastatic disease. However, since no biomarker for the identification of patients with true oligometastatic disease is clinically available, the diagnosis of oligometastatic disease is based solely on imaging findings. A small number of metastases on imaging could represent different clinical scenarios, which are associated with different prognoses and might require different treatment strategies. 20 international experts including 19 members of the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer OligoCare project developed a comprehensive system for characterisation and classification of oligometastatic disease. We first did a systematic review of the literature to identify inclusion and exclusion criteria of prospective interventional oligometastatic disease clinical trials. Next, we used a Delphi consensus process to select a total of 17 oligometastatic disease characterisation factors that should be assessed in all patients treated with radical local therapy for oligometastatic disease, both within and outside of clinical trials. Using a second round of the Delphi method, we established a decision tree for oligometastatic disease classification together with a nomenclature. We agreed oligometastatic disease as the overall umbrella term. A history of polymetastatic disease before diagnosis of oligometastatic disease was used as the criterion to differentiate between induced oligometastatic disease (previous history of polymetastatic disease) and genuine oligometastatic disease (no history of polymetastatic disease). We further subclassified genuine oligometastatic disease into repeat oligometastatic disease (previous history of oligometastatic disease) and de-novo oligometastatic disease (first time diagnosis of oligometastatic disease). In de-novo oligometastatic disease, we differentiated between synchronous and metachronous oligometastatic disease. We did a final subclassification into oligorecurrence, oligoprogression, and oligopersistence, considering whether oligometastatic disease is diagnosed during a treatment-free interval or during active systemic therapy and whether or not an oligometastatic lesion is progressing on current imaging. This oligometastatic disease classification and nomenclature needs to be prospectively evaluated by the OligoCare study.

472 citations


Journal ArticleDOI
TL;DR: In patients with peripheral artery disease who had undergone lower-extremity revascularization, rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes than aspirin alone.
Abstract: Background Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and ...

451 citations


Journal ArticleDOI
TL;DR: The conversion of biomass derived FUR and HMF through unconventional (transfer hydrogenation, photocatalytic and electrocatalytic) catalytic processes promoted by heterogeneous catalytic systems are discussed.
Abstract: Furans represent one of the most important classes of intermediates in the conversion of non-edible lignocellulosic biomass into bio-based chemicals and fuels. At present, bio-furan derivatives are generally obtained from cellulose and hemicellulose fractions of biomass via the acid-catalyzed dehydration of their relative C6-C5 sugars and then converted into a wide range of products. Furfural (FUR) and 5-hydroxymethylfurfural (HMF) are surely the most used furan-based feedstocks since their chemical structure allows the preparation of various high-value-added chemicals. Among several well-established catalytic approaches, hydrogenation and oxygenation processes have been efficiently adopted for upgrading furans; however, harsh reaction conditions are generally required. In this review, we aim to discuss the conversion of biomass derived FUR and HMF through unconventional (transfer hydrogenation, photocatalytic and electrocatalytic) catalytic processes promoted by heterogeneous catalytic systems. The reaction conditions adopted, the chemical nature and the physico-chemical properties of the most employed heterogeneous systems in enhancing the catalytic activity and in driving the selectivity to desired products are presented and compared. At the same time, the latest results in the production of FUR and HMF through novel environmental friendly processes starting from lignocellulose as well as from wastes and by-products obtained in the processing of biomass are also overviewed.

441 citations


Journal ArticleDOI
TL;DR: This review sets the basis for a better understanding of the psychological conditions of workers during the pandemic, integrating individual and social perspectives, and providing insight into possible individual, social, and occupational approaches to this “psychological pandemic”.
Abstract: The Coronavirus Disease 2019 (COVID-19) pandemic has deeply altered social and working environments in several ways. Social distancing policies, mandatory lockdowns, isolation periods, and anxiety of getting sick, along with the suspension of productive activity, loss of income, and fear of the future, jointly influence the mental health of citizens and workers. Workplace aspects can play a crucial role on moderating or worsening mental health of people facing this pandemic scenario. The purpose of this literature review is to deepen the psychological aspects linked to workplace factors, following the epidemic rise of COVID-19, in order to address upcoming psychological critical issues in the workplaces. We performed a literature search using Google Scholar, PubMed, and Scopus, selecting papers focusing on workers' psychological problems that can be related to the workplace during the pandemic. Thirty-five articles were included. Mental issues related to the health emergency, such as anxiety, depression, post-traumatic stress disorder (PTSD), and sleep disorders are more likely to affect healthcare workers, especially those on the frontline, migrant workers, and workers in contact with the public. Job insecurity, long periods of isolation, and uncertainty of the future worsen the psychological condition, especially in younger people and in those with a higher educational background. Multiple organizational and work-related interventions can mitigate this scenario, such as the improvement of workplace infrastructures, the adoption of correct and shared anti-contagion measures, including regular personal protective equipment (PPE) supply, and the implementation of resilience training programs. This review sets the basis for a better understanding of the psychological conditions of workers during the pandemic, integrating individual and social perspectives, and providing insight into possible individual, social, and occupational approaches to this "psychological pandemic".

418 citations


Journal ArticleDOI
Wannes Hubau1, Wannes Hubau2, Wannes Hubau3, Simon L. Lewis4, Simon L. Lewis2, Oliver L. Phillips2, Kofi Affum-Baffoe5, Hans Beeckman3, Aida Cuni-Sanchez6, Aida Cuni-Sanchez4, Armandu K. Daniels, Corneille E. N. Ewango7, Corneille E. N. Ewango8, Sophie Fauset9, Jaccques M. Mukinzi10, Jaccques M. Mukinzi7, Douglas Sheil11, Bonaventure Sonké12, Martin J. P. Sullivan13, Martin J. P. Sullivan2, Terry Sunderland14, Terry Sunderland15, Hermann Taedoumg16, Hermann Taedoumg12, Sean C. Thomas17, Lee J. T. White18, Katharine Abernethy18, Stephen Adu-Bredu19, C. Amani14, Timothy R. Baker2, Lindsay F. Banin, Fidèle Baya, Serge K. Begne2, Serge K. Begne12, Amy C. Bennett2, Fabrice Bénédet20, Fabrice Bénédet21, Robert Bitariho22, Yannick Enock Bocko23, Pascal Boeckx1, Patrick Boundja14, Patrick Boundja7, Roel J. W. Brienen2, Terry Brncic7, Eric Chezeaux, George B. Chuyong24, Connie J. Clark25, Murray Collins26, James A. Comiskey27, James A. Comiskey28, David A. Coomes29, Greta C. Dargie2, Thalès de Haulleville3, Marie Noel Djuikouo Kamdem24, Jean-Louis Doucet30, Adriane Esquivel-Muelbert31, Adriane Esquivel-Muelbert2, Ted R. Feldpausch32, Alusine Fofanah, Ernest G. Foli19, Martin Gilpin2, Emanuel Gloor2, Christelle Gonmadje, Sylvie Gourlet-Fleury21, Sylvie Gourlet-Fleury20, Jefferson S. Hall33, Alan Hamilton34, David Harris35, Terese B. Hart36, Terese B. Hart37, Mireille Breuer-Ndoundou Hockemba7, Annette Hladik, Suspense Averti Ifo23, Kathryn J. Jeffery18, Tommaso Jucker38, Emmanuel Kasongo Yakusu8, Emmanuel Kasongo Yakusu1, Emmanuel Kasongo Yakusu3, Elizabeth Kearsley1, Elizabeth Kearsley3, David Kenfack33, Alexander K. Koch4, Alexander K. Koch39, Miguel E. Leal7, Aurora Levesley2, Jeremy A. Lindsell40, Janvier Lisingo8, Gabriela Lopez-Gonzalez2, Jon C. Lovett2, Jon C. Lovett41, Jean-Remy Makana8, Yadvinder Malhi42, Andrew R. Marshall43, Andrew R. Marshall6, Jim Martin44, Emanuel H. Martin, Faustin M. Mbayu8, Vincent P. Medjibe25, Vianet Mihindou, Edward T. A. Mitchard26, Sam Moore42, Pantaleo K. T. Munishi45, Natacha Nssi Bengone, Lucas Ojo, Fidèle Evouna Ondo, Kelvin S.-H. Peh46, Kelvin S.-H. Peh29, Georgia Pickavance2, Axel Dalberg Poulsen35, John R. Poulsen25, Lan Qie47, Lan Qie2, Jan Reitsma, Francesco Rovero48, Michael D. Swaine49, Joey Talbot2, James Taplin50, David Taylor51, Duncan W. Thomas52, Benjamin Toirambe3, John Tshibamba Mukendi8, John Tshibamba Mukendi3, Darlington Tuagben, Peter M. Umunay7, Peter M. Umunay53, Geertje M. F. van der Heijden54, Hans Verbeeck1, Jason Vleminckx55, Jason Vleminckx56, Simon Willcock57, Hannsjörg Wöll, John T. Woods58, Lise Zemagho12 
Ghent University1, University of Leeds2, Royal Museum for Central Africa3, University College London4, Forestry Commission5, University of York6, Wildlife Conservation Society7, University of Kisangani8, University of Plymouth9, World Wide Fund for Nature10, Norwegian University of Life Sciences11, University of Yaoundé I12, Manchester Metropolitan University13, Center for International Forestry Research14, University of British Columbia15, Bioversity International16, University of Toronto17, University of Stirling18, Forestry Research Institute of Ghana19, University of Montpellier20, Centre de coopération internationale en recherche agronomique pour le développement21, Mbarara University of Science and Technology22, Marien Ngouabi University23, University of Buea24, Duke University25, University of Edinburgh26, Smithsonian Institution27, National Park Service28, University of Cambridge29, Gembloux Agro-Bio Tech30, University of Birmingham31, University of Exeter32, Smithsonian Tropical Research Institute33, Chinese Academy of Sciences34, Royal Botanic Garden Edinburgh35, American Museum of Natural History36, African Wildlife Foundation37, University of Bristol38, University of Hong Kong39, Royal Society for the Protection of Birds40, Royal Botanic Gardens41, Environmental Change Institute42, University of the Sunshine Coast43, Fleming College44, Sokoine University of Agriculture45, University of Southampton46, University of Lincoln47, University of Florence48, University of Aberdeen49, Innovate UK50, National University of Singapore51, Washington State University Vancouver52, Yale University53, University of Nottingham54, Université libre de Bruxelles55, Florida International University56, Bangor University57, University of Liberia58
04 Mar 2020-Nature
TL;DR: Overall, the uptake of carbon into Earth’s intact tropical forests peaked in the 1990s and independent observations indicating greater recent carbon uptake into the Northern Hemisphere landmass reinforce the conclusion that the intact tropical forest carbon sink has already peaked.
Abstract: Structurally intact tropical forests sequestered about half of the global terrestrial carbon uptake over the 1990s and early 2000s, removing about 15 per cent of anthropogenic carbon dioxide emissions. Climate-driven vegetation models typically predict that this tropical forest ‘carbon sink’ will continue for decades. Here we assess trends in the carbon sink using 244 structurally intact African tropical forests spanning 11 countries, compare them with 321 published plots from Amazonia and investigate the underlying drivers of the trends. The carbon sink in live aboveground biomass in intact African tropical forests has been stable for the three decades to 2015, at 0.66 tonnes of carbon per hectare per year (95 per cent confidence interval 0.53–0.79), in contrast to the long-term decline in Amazonian forests. Therefore the carbon sink responses of Earth’s two largest expanses of tropical forest have diverged. The difference is largely driven by carbon losses from tree mortality, with no detectable multi-decadal trend in Africa and a long-term increase in Amazonia. Both continents show increasing tree growth, consistent with the expected net effect of rising atmospheric carbon dioxide and air temperature. Despite the past stability of the African carbon sink, our most intensively monitored plots suggest a post-2010 increase in carbon losses, delayed compared to Amazonia, indicating asynchronous carbon sink saturation on the two continents. A statistical model including carbon dioxide, temperature, drought and forest dynamics accounts for the observed trends and indicates a long-term future decline in the African sink, whereas the Amazonian sink continues to weaken rapidly. Overall, the uptake of carbon into Earth’s intact tropical forests peaked in the 1990s. Given that the global terrestrial carbon sink is increasing in size, independent observations indicating greater recent carbon uptake into the Northern Hemisphere landmass reinforce our conclusion that the intact tropical forest carbon sink has already peaked. This saturation and ongoing decline of the tropical forest carbon sink has consequences for policies intended to stabilize Earth’s climate.

395 citations


Journal ArticleDOI
TL;DR: The association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore anti-viral mechanisms.
Abstract: BACKGROUNDCoronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options.METHODSWe performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes.RESULTSPatients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of CD8+ T cells toward a terminally differentiated/senescent phenotype. In agreement, CD4+ T and CD8+ T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A-expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells.CONCLUSIONThe association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms.FUNDINGThis study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the "Excellence Departments 2018-2022 Project") derived from Ministero dell'Istruzione, dell'Universita e della Ricerca (Italy).

Journal ArticleDOI
Iacopo Olivotto1, Artur Oreziak, Roberto Barriales-Villa, Theodore P. Abraham2, Ahmad Masri3, Pablo García-Pavía4, Pablo García-Pavía5, Sara Saberi6, Neal K. Lakdawala7, Matthew T. Wheeler8, Anjali T. Owens9, Milos Kubanek, Wojciech Wojakowski10, Morten Kvistholm Jensen11, Juan Ramón Gimeno-Blanes, Kia Afshar12, Jonathan Myers8, Jonathan Myers13, Sheila M. Hegde7, Scott D. Solomon7, Amy J. Sehnert, David Zhang, Wanying Li, Mondira Bhattacharya, Jay M. Edelberg, Cynthia Burstein Waldman, Steven J. Lester14, Andrew Wang15, Carolyn Y. Ho7, Daniel Jacoby16, Jozef Bartunek, Antoine Bondue, Emeline Van Craenenbroeck, David Zemanek, Morten Søndergaard Jensen17, Jens Mogensen, Jens Jakob Thune, Philippe Charron, Albert Hagège, Olivier Lairez, Jean Noël Trochu, Christoph Axthelm, Hans Dirk Duengen, Norbert Frey, Veselin Mitrovic, Michael Preusch, Jeanette Schulz-Menger, Tim Seidler, Michael Arad, Majdi Halabi, Amos Katz, Daniel Monakier, Offir Paz, Samuel Viskin, Donna R. Zwas, Hans-Peter Brunner-La Rocca, Michelle Michels, Dariusz Dudek, Zofia Oko-Sarnowska, Nuno Cardim, Helder Pereira, Pablo García Pavia, Juan Ramon Gimeno Blanes, Rafael Hidalgo Urbano, Luis Miguel Rincón Diaz, Perry M. Elliott, Zaheer Yousef, Theodore Abraham18, Paulino Alvarez, Richard G. Bach, Richard C. Becker, Lubna Choudhury, David Fermin, John L. Jefferies, Christopher M. Kramer, Neal K. Lakdawala19, Steven Lester14, Ali J. Marian, Mathew S. Maurer, Sherif F. Nagueh, David R. Owens, Florian Rader, Mark V. Sherrid, Jamshid Shirani, John Symanski, Aslan T. Turer, Omar Wever-Pinzon, Timothy C. Wong, Mohamad H. Yamani 
TL;DR: Treatment with mavacamten improved exercise capacity, LVOT obstruction, NYHA functional class, and health status in patients with obstructive hypertrophic cardiomyopathy and highlights the benefits of disease-specific treatment for this condition.

Journal ArticleDOI
TL;DR: To gain better information about appropriate anti-inflammatory treatments, mostly used in rheumatology for COVID-19, the attention is focused on the structural features of Sars-CoV-2, the host immune response against SARS-Cov-2 and its association with the cytokine storm.
Abstract: In the Wuhan Province of China, in December 2019, the novel coronavirus 2019 (COVID-19) has caused a severe involvement of the lower respiratory tract leading to an acute respiratory syndrome. Subsequently, coronavirus 2 (SARS-CoV-2) provoked a pandemic which is considered a life-threatening disease. The SARS-CoV-2, a family member of betacoronaviruses, possesses single-stranded positive-sense RNA with typical structural proteins, involving the envelope, membrane, nucleocapsid and spike proteins that are responsible for the viral infectivity, and nonstructural proteins. The effectual host immune response including innate and adaptive immunity against SARS-Cov-2 seems crucial to control and resolve the viral infection. However, the severity and outcome of the COVID-19 might be associated with the excessive production of proinflammatory cytokines “cytokine storm” leading to an acute respiratory distress syndrome. Regretfully, the exact pathophysiology and treatment, especially for the severe COVID-19, is still uncertain. The results of preliminary studies have shown that immune-modulatory or immune-suppressive treatments such as hydroxychloroquine, interleukin (IL)-6 and IL-1 antagonists, commonly used in rheumatology, might be considered as treatment choices for COVID-19, particularly in severe disease. In this review, to gain better information about appropriate anti-inflammatory treatments, mostly used in rheumatology for COVID-19, we have focused the attention on the structural features of SARS-CoV-2, the host immune response against SARS-CoV-2 and its association with the cytokine storm.

Journal ArticleDOI
TL;DR: In this paper, the authors derive a parametrization of linear feedback systems that paves the way to solve important control problems using data-dependent linear matrix inequalities only, which is remarkable in that no explicit system's matrices identification is required.
Abstract: In a paper by Willems et al., it was shown that persistently exciting data can be used to represent the input-output behavior of a linear system. Based on this fundamental result, we derive a parametrization of linear feedback systems that paves the way to solve important control problems using data-dependent linear matrix inequalities only. The result is remarkable in that no explicit system's matrices identification is required. The examples of control problems we solve include the state and output feedback stabilization, and the linear quadratic regulation problem. We also discuss robustness to noise-corrupted measurements and show how the approach can be used to stabilize unstable equilibria of nonlinear systems.

Journal ArticleDOI
Elsa Bernard1, Yasuhito Nannya2, Robert P. Hasserjian3, Sean M. Devlin1, Heinz Tuechler, Juan S. Medina-Martinez1, Tetsuichi Yoshizato2, Yusuke Shiozawa2, Ryunosuke Saiki2, Luca Malcovati4, Max Levine1, Juan E. Arango1, Yangyu Zhou1, Francesc Solé, Catherine Cargo5, Detlef Haase6, Maria Creignou7, Ulrich Germing8, Yanming Zhang1, Gunes Gundem1, Araxe Sarian1, Arjan A. van de Loosdrecht, Martin Jädersten7, Magnus Tobiasson7, Olivier Kosmider9, Matilde Y. Follo10, Felicitas Thol11, Ronald Feitosa Pinheiro12, Valeria Santini13, Ioannis Kotsianidis14, Jacqueline Boultwood15, Fabio P.S. Santos, Julie Schanz6, Senji Kasahara, Takayuki Ishikawa, Hisashi Tsurumi16, Akifumi Takaori-Kondo2, Toru Kiguchi, Chantana Polprasert17, John M. Bennett18, Virginia M. Klimek1, Michael R. Savona19, Monika Belickova, Christina Ganster6, Laura Palomo, Guillermo Sanz20, Lionel Ades21, Matteo G. Della Porta, Alexandra Smith22, Yesenia Werner1, Minal Patel1, Agnes Viale1, Katelynd Vanness1, Donna Neuberg3, Kristen E. Stevenson3, Kamal Menghrajani1, Kelly L. Bolton1, Pierre Fenaux21, Andrea Pellagatti15, Uwe Platzbecker23, Michael Heuser11, Peter Valent24, Shigeru Chiba25, Yasushi Miyazaki26, Carlo Finelli10, Maria Teresa Voso27, Lee Yung Shih28, Michaela Fontenay9, Joop H. Jansen29, José Cervera, Yoshiko Atsuta, Norbert Gattermann8, Benjamin L. Ebert30, Rafael Bejar31, Peter L. Greenberg32, Mario Cazzola4, Eva Hellström-Lindberg7, Seishi Ogawa2, Elli Papaemmanuil1 
TL;DR: Clinical sequencing across a large prospective cohort of patients with myelodysplasic syndrome uncovers distinct associations between the mono- and biallelic states of TP53 and clinical presentation.
Abstract: Tumor protein p53 (TP53) is the most frequently mutated gene in cancer1,2. In patients with myelodysplastic syndromes (MDS), TP53 mutations are associated with high-risk disease3,4, rapid transformation to acute myeloid leukemia (AML)5, resistance to conventional therapies6–8 and dismal outcomes9. Consistent with the tumor-suppressive role of TP53, patients harbor both mono- and biallelic mutations10. However, the biological and clinical implications of TP53 allelic state have not been fully investigated in MDS or any other cancer type. We analyzed 3,324 patients with MDS for TP53 mutations and allelic imbalances and delineated two subsets of patients with distinct phenotypes and outcomes. One-third of TP53-mutated patients had monoallelic mutations whereas two-thirds had multiple hits (multi-hit) consistent with biallelic targeting. Established associations with complex karyotype, few co-occurring mutations, high-risk presentation and poor outcomes were specific to multi-hit patients only. TP53 multi-hit state predicted risk of death and leukemic transformation independently of the Revised International Prognostic Scoring System (IPSS-R)11. Surprisingly, monoallelic patients did not differ from TP53 wild-type patients in outcomes and response to therapy. This study shows that consideration of TP53 allelic state is critical for diagnostic and prognostic precision in MDS as well as in future correlative studies of treatment response. Clinical sequencing across a large prospective cohort of patients with myelodysplasic syndrome uncovers distinct associations between the mono- and biallelic states of TP53 and clinical presentation

Journal ArticleDOI
TL;DR: Analysis of RNA sequences from bronchoalveolar lavage fluids obtained from coronavirus-infected patients suggests that both APOBECs and ADARs are involved in coronav virus genome editing, a process that may shape the fate of both virus and patient.
Abstract: The COVID-19 outbreak has become a global health risk, and understanding the response of the host to the SARS-CoV-2 virus will help to combat the disease. RNA editing by host deaminases is an innate restriction process to counter virus infection, but it is not yet known whether this process operates against coronaviruses. Here, we analyze RNA sequences from bronchoalveolar lavage fluids obtained from coronavirus-infected patients. We identify nucleotide changes that may be signatures of RNA editing: adenosine-to-inosine changes from ADAR deaminases and cytosine-to-uracil changes from APOBEC deaminases. Mutational analysis of genomes from different strains of Coronaviridae from human hosts reveals mutational patterns consistent with those observed in the transcriptomic data. However, the reduced ADAR signature in these data raises the possibility that ADARs might be more effective than APOBECs in restricting viral propagation. Our results thus suggest that both APOBECs and ADARs are involved in coronavirus genome editing, a process that may shape the fate of both virus and patient.

Journal ArticleDOI
Dinesh Khanna1, Celia J. F. Lin2, Daniel E. Furst3, Jonathan G. Goldin3, Grace Kim3, Masataka Kuwana4, Yannick Allanore5, Marco Matucci-Cerinic6, Oliver Distler7, Yoshihito Shima8, Jacob M van Laar9, Helen Spotswood10, Bridget Wagner2, Jeffrey Siegel2, Angelika Jahreis2, Christopher P. Denton11, Eleonora Lucero, Bernardo A. Pons-Estel, Mariano Rivero, Guillermo Tate, Vanessa Smith, Ellen De Langhe, Rasho Rashkov, Anastas Batalov, Ivan Goranov, Rumen Stoilov, James V. Dunne, Sindhu R. Johnson, Janet E. Pope, Dušanka Martinović Kaliterna, Mette Mogensen, Anne Braae Olesen, Joerg Henes, Ulf Müller-Ladner, Gabriela Riemekasten, Alla Skapenko, Panayiotis G. Vlachoyiannopoulos, Emese Kiss, Tünde Minier, Lorenzo Beretta, Elisa Gremese, Gabriele Valentini, Yoshihide Asano, Tatsuya Atsumi, Hironobu Ihn, Tomonori Ishii, Osamu Ishikawa, Hiroki Takahashi, Kazuhiko Takehara, Yoshiya Tanaka, Yoshioki Yamasaki, Loreta Bukauskiene, Irena Butrimiene, Gabriel Medrano Ramirez, Cesar Ramos-Remus, Tatiana Sofia Rodriguez Reyna, Jeska K de Vries-Bouwstra, Bogdan Batko, Sławomir Jeka, Eugeniusz J. Kucharz, Maria Majdan, Marzena Olesińska, Zaneta Smolenska, Jose Alves, Maria José Santos, C. Mihai, Simona Rednic, Ivan Castellvi Barranco, Francisco Javier Lopez Longo, Carmen Simeon Aznar, Patricia Carreira, Ulrich A. Walker, Emma Derrett-Smith, Bridget Griffiths, Neil McKay, Jacob Aelion, Michael S. Borofsky, Roy Fleischmann, Joseph Z. Forstot, Suzanne Kafaja, M. Faisal Khan, Michael D. Kohen, Richard J. Martin, Fabian Mendoza-Ballesteros, Alireza Nami, Shirley Pang, Grissel Rios, Robert W. Simms, Keith M. Sullivan, Virginia D. Steen 
TL;DR: Findings for the secondary endpoint of FVC% predicted indicate that tocilizumab might preserve lung function in people with early SSc-ILD and elevated acute-phase reactants.

Journal ArticleDOI
TL;DR: Luspatercept reduced the severity of anemia in patients with lower-risk myelodysplastic syndromes with ring sideroblasts who had been receiving regular red-cell transfusions and who had disease that was refractory to or unlikely to respond to erythropoiesis-stimulating agents or who had discontinued such agents owing to an adverse event.
Abstract: Background Patients with anemia and lower-risk myelodysplastic syndromes in whom erythropoiesis-stimulating agent therapy is not effective generally become dependent on red-cell transfusio...

Journal ArticleDOI
Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam, Federico Ambrogi  +2248 moreInstitutions (155)
TL;DR: For the first time, predictions from pythia8 obtained with tunes based on NLO or NNLO PDFs are shown to reliably describe minimum-bias and underlying-event data with a similar level of agreement to predictions from tunes using LO PDF sets.
Abstract: New sets of CMS underlying-event parameters (“tunes”) are presented for the pythia8 event generator. These tunes use the NNPDF3.1 parton distribution functions (PDFs) at leading (LO), next-to-leading (NLO), or next-to-next-to-leading (NNLO) orders in perturbative quantum chromodynamics, and the strong coupling evolution at LO or NLO. Measurements of charged-particle multiplicity and transverse momentum densities at various hadron collision energies are fit simultaneously to determine the parameters of the tunes. Comparisons of the predictions of the new tunes are provided for observables sensitive to the event shapes at LEP, global underlying event, soft multiparton interactions, and double-parton scattering contributions. In addition, comparisons are made for observables measured in various specific processes, such as multijet, Drell–Yan, and top quark-antiquark pair production including jet substructure observables. The simulation of the underlying event provided by the new tunes is interfaced to a higher-order matrix-element calculation. For the first time, predictions from pythia8 obtained with tunes based on NLO or NNLO PDFs are shown to reliably describe minimum-bias and underlying-event data with a similar level of agreement to predictions from tunes using LO PDF sets.

Journal ArticleDOI
TL;DR: In this article, tensor network methods are applied to the study of lattice gauge theories together with some results on Abelian and non-Abelian lattice-gauge theories.
Abstract: Lattice gauge theories, which originated from particle physics in the context of Quantum Chromodynamics (QCD), provide an important intellectual stimulus to further develop quantum information technologies. While one long-term goal is the reliable quantum simulation of currently intractable aspects of QCD itself, lattice gauge theories also play an important role in condensed matter physics and in quantum information science. In this way, lattice gauge theories provide both motivation and a framework for interdisciplinary research towards the development of special purpose digital and analog quantum simulators, and ultimately of scalable universal quantum computers. In this manuscript, recent results and new tools from a quantum science approach to study lattice gauge theories are reviewed. Two new complementary approaches are discussed: first, tensor network methods are presented – a classical simulation approach – applied to the study of lattice gauge theories together with some results on Abelian and non-Abelian lattice gauge theories. Then, recent proposals for the implementation of lattice gauge theory quantum simulators in different quantum hardware are reported, e.g., trapped ions, Rydberg atoms, and superconducting circuits. Finally, the first proof-of-principle trapped ions experimental quantum simulations of the Schwinger model are reviewed.

Journal ArticleDOI
TL;DR: Increased D-dimer levels have gained particular attention as a predictor of the development of acute respiratory distress syndrome (ARDS), the need for admission to an intensive care unit (ICU) or death1-5, and many issues remain to be addressed.
Abstract: Arrived: 05/04/2020 Accepted: 07/04/2020 Correspondence: Marco Marietta e-mail: marco.marietta@unimore.it 1Department of Oncology and Haematology, University Hospital, Modena; 2Department of Medicine and Surgery, “Insubria” University, Varese; 3IRCCS “Ca’ Granda Maggiore” Hospital Foundation, “Angelo Bianchi Bonomi” Haemophilia and Thrombosis Center and “Fondazione Luigi Villa”, Milan; 4Department of Medicine and Translational Surgery, “Università Cattolica del Sacro Cuore”, Faculty of Medicine and Surgery, Rome; 5Department of Diagnostic Imaging, Oncological Radiotherapy and Haematology, Foundation \"A. Gemelli\" IRCCS University Hospital, Rome; 6Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia; 7Immunohematology and Transfusion Medicine Department, “ASST Papa Giovanni XXIII”, Bergamo; 8Department of Experimental and Clinical Medicine, “Careggi” University Hospital, University of Florence, Italy The ongoing pandemic of Coronavirus disease 2019 (COVID-19) is severely challenging healthcare systems all around the world, with the need to provide intensive care to a previously inconceivable number of patients. The clinical spectrum of the disease is very wide, ranging from minor, unspecific symptoms, such as fever, dry cough and diarrhoea, sometimes combined with mild pneumonia and mild dyspnoea, to severe pneumonia with dyspnoea, tachypnoea and disturbed gas exchange, leading in approximately 5% of infected patients to severe lung dysfunction, a need for ventilation, shock or multiple (extra pulmonary) organ failure1. Among the several clinical and biochemical parameters associated with poor prognosis, increased D-dimer levels have gained particular attention as a predictor of the development of acute respiratory distress syndrome (ARDS), the need for admission to an intensive care unit (ICU) or death1-5. On the other hand, disease severity also correlates with pro-inf lammatory cytokines (i.e., IL-2, IL6, IL-7, IL-10, G-CSF, IP-10, MCP-1, MIP-1A and TNF-α), although it is not yet clear what is the cause of such a cytokine storm6. These findings are consistent with the already demonstrated close connection between thrombosis and inf lammation7,8, two processes that mutually reinforce each other. Indeed, both coagulation factors (proand anti-coagulants)9-11 and platelets12-14 are directly implicated in the modulation of the host immune response, displaying proinf lammatory functions that are independent from their haemostatic effects. All the above issues have been instrumental in spreading the feeling that COVID-19 is associated with the classical syndrome named disseminated intravascular coagulation (DIC) and the subsequent consumption coagulopathy. Moreover, it has been shown that heparin, beside its anticoagulant effects, also displays an anti-inf lammatory action, various immunomodulatory properties, and protects glycocalyx from shedding15. It has also been suggested that dipyridamole, an antiplatelet drug with antiviral and antioxidant properties, has beneficial effects in patients with COVID-1916. Despite such a tight interconnection between inf lammation and haemostasis abnormalities, no good evidence is available of the efficacy/safety of heparin and/or antiplatelet agents on sepsis patients, and many issues remain to be addressed, such as the proper timing, dosages and administration scheme of antithrombotic drugs17-19. Nevertheless, very recent data showed that low molecular weight heparin (LMWH) or unfractionated heparin (UFH) at prophylactic doses are associated with a reduced 28-day mortality in more severe COVID-19 patients displaying a sepsis-induced coagulopathy (SIC) score ≥4 (40.0% vs 64.2%, p=0.029) or D-dimer levels >6-fold the upper limit of © SI MT IP RO Sr l

Journal ArticleDOI
TL;DR: The goal of this work is to shed light on the challenges and open problems of Quantum Internet design and introduce quantum teleportation as the key strategy for transmitting quantum information without physically transferring the particle that stores the quantum information or violating the principles of quantum mechanics.
Abstract: The Quantum Internet, a network interconnecting remote quantum devices through quantum links in synergy with classical ones, is envisioned as the final stage of the quantum revolution, opening fundamentally new communications and computing capabilities. But the Quantum Internet is governed by the laws of quantum mechanics. Phenomena with no counterpart in classical networks, such as no-cloning, quantum measurement, entanglement and quantum teleportation, impose new challenging constraints for network design. Specifically, classical network functionalities are based on the assumption that classical information can be safely read and copied. However, this assumption does not hold in the Quantum Internet. As a consequence, its design requires a major network-paradigm shift to harness the quantum mechanics specificities. The goal of this work is to shed light on the challenges and open problems of Quantum Internet design. We first introduce some basic knowledge of quantum mechanics, needed to understand the differences between a classical and a quantum network. Then, we introduce quantum teleportation as the key strategy for transmitting quantum information without physically transferring the particle that stores the quantum information or violating the principles of quantum mechanics. Finally, the key research challenges to design quantum communication networks are discussed.

Journal ArticleDOI
Yousef Abou El-Neaj1, Cristiano Alpigiani2, Sana Amairi-Pyka3, Henrique Araujo4, Antun Balaž5, Angelo Bassi6, Lars Bathe-Peters7, Baptiste Battelier8, Aleksandar Belić5, Elliot Bentine9, Jose Bernabeu10, Andrea Bertoldi8, Robert Bingham11, Robert Bingham12, Diego Blas13, Vasiliki Bolpasi14, Kai Bongs15, Sougato Bose16, Philippe Bouyer8, T. J. V. Bowcock17, William B. Bowden18, Oliver Buchmueller4, Clare Burrage19, Xavier Calmet20, Benjamin Canuel8, Laurentiu Ioan Caramete, Andrew Carroll17, Giancarlo Cella6, Vassilis Charmandaris14, S. Chattopadhyay21, S. Chattopadhyay22, Xuzong Chen23, Maria Luisa Chiofalo24, J. P. Coleman17, J. P. Cotter4, Y. Cui25, Andrei Derevianko26, Albert De Roeck27, Goran S. Djordjevic28, P. J. Dornan4, Michael Doser27, Ioannis Drougkakis14, Jacob Dunningham20, Ioana Dutan, Sajan Easo11, G. Elertas17, John Ellis13, John Ellis27, John Ellis29, Mai El Sawy30, Mai El Sawy31, Farida Fassi, D. Felea, Chen Hao Feng8, R. L. Flack16, Christopher J. Foot9, Ivette Fuentes19, Naceur Gaaloul32, A. Gauguet33, Remi Geiger34, Valerie Gibson35, Gian F. Giudice27, J. Goldwin15, O. A. Grachov36, Peter W. Graham37, Dario Grasso24, Maurits van der Grinten11, Mustafa Gündoğan3, Martin G. Haehnelt35, Tiffany Harte35, Aurélien Hees34, Richard Hobson18, Jason M. Hogan37, Bodil Holst38, Michael Holynski15, Mark A. Kasevich37, Bradley J. Kavanagh39, Wolf von Klitzing14, Tim Kovachy40, Benjamin Krikler41, Markus Krutzik3, Marek Lewicki13, Marek Lewicki42, Yu-Hung Lien16, Miaoyuan Liu23, Giuseppe Gaetano Luciano6, Alain Magnon43, Mohammed Mahmoud44, Sudhir Malik4, Christopher McCabe13, J. W. Mitchell22, Julia Pahl3, Debapriya Pal14, Saurabh Pandey14, Dimitris G. Papazoglou45, Mauro Paternostro46, Bjoern Penning47, Achim Peters3, Marco Prevedelli48, Vishnupriya Puthiya-Veettil49, J. J. Quenby4, Ernst M. Rasel32, Sean Ravenhall9, Jack Ringwood17, Albert Roura50, D. O. Sabulsky8, M. Sameed51, Ben Sauer4, Stefan A. Schäffer52, Stephan Schiller53, Vladimir Schkolnik3, Dennis Schlippert32, Christian Schubert32, Haifa Rejeb Sfar, Armin Shayeghi54, Ian Shipsey9, Carla Signorini24, Yeshpal Singh15, Marcelle Soares-Santos47, Fiodor Sorrentino6, T. J. Sumner4, Konstantinos Tassis14, S. Tentindo55, Guglielmo M. Tino6, Guglielmo M. Tino56, Jonathan N. Tinsley56, James Unwin57, Tristan Valenzuela11, Georgios Vasilakis14, Ville Vaskonen13, Ville Vaskonen29, Christian Vogt58, Alex Webber-Date17, André Wenzlawski59, Patrick Windpassinger59, Marian Woltmann58, Efe Yazgan60, Ming Sheng Zhan60, Xinhao Zou8, Jure Zupan61 
Harvard University1, University of Washington2, Humboldt University of Berlin3, Imperial College London4, University of Belgrade5, Istituto Nazionale di Fisica Nucleare6, Technical University of Berlin7, University of Bordeaux8, University of Oxford9, University of Valencia10, Rutherford Appleton Laboratory11, University of Strathclyde12, King's College London13, Foundation for Research & Technology – Hellas14, University of Birmingham15, University College London16, University of Liverpool17, National Physical Laboratory18, University of Nottingham19, University of Sussex20, Fermilab21, Northern Illinois University22, Peking University23, University of Pisa24, University of California, Riverside25, University of Nevada, Reno26, CERN27, University of Niš28, National Institute of Chemical Physics and Biophysics29, Beni-Suef University30, British University in Egypt31, Leibniz University of Hanover32, Paul Sabatier University33, University of Paris34, University of Cambridge35, Wayne State University36, Stanford University37, University of Bergen38, University of Amsterdam39, Northwestern University40, University of Bristol41, University of Warsaw42, University of Illinois at Urbana–Champaign43, Fayoum University44, University of Crete45, Queen's University Belfast46, Brandeis University47, University of Bologna48, Cochin University of Science and Technology49, German Aerospace Center50, University of Manchester51, University of Copenhagen52, University of Düsseldorf53, University of Vienna54, Florida State University55, University of Florence56, University of Illinois at Chicago57, University of Bremen58, University of Mainz59, Chinese Academy of Sciences60, University of Cincinnati61
TL;DR: The Atomic Experiment for Dark Matter and Gravity Exploration (AEDGE) as mentioned in this paper is a space experiment using cold atoms to search for ultra-light dark matter, and to detect gravitational waves in the frequency range between the most sensitive ranges of LISA and the terrestrial LIGO/Virgo/KAGRA/INDIGO experiments.
Abstract: We propose in this White Paper a concept for a space experiment using cold atoms to search for ultra-light dark matter, and to detect gravitational waves in the frequency range between the most sensitive ranges of LISA and the terrestrial LIGO/Virgo/KAGRA/INDIGO experiments. This interdisciplinary experiment, called Atomic Experiment for Dark Matter and Gravity Exploration (AEDGE), will also complement other planned searches for dark matter, and exploit synergies with other gravitational wave detectors. We give examples of the extended range of sensitivity to ultra-light dark matter offered by AEDGE, and how its gravitational-wave measurements could explore the assembly of super-massive black holes, first-order phase transitions in the early universe and cosmic strings. AEDGE will be based upon technologies now being developed for terrestrial experiments using cold atoms, and will benefit from the space experience obtained with, e.g., LISA and cold atom experiments in microgravity.

Journal ArticleDOI
TL;DR: The Symbol Digit Modalities Test, or its computer-based analogues, can be used to monitor episodes of acute disease activity and data increasingly show that cognitive processing speed and memory are amenable to cognitive training interventions.
Abstract: Multiple sclerosis is a chronic, demyelinating disease of the CNS. Cognitive impairment is a sometimes neglected, yet common, sign and symptom with a profound effect on instrumental activities of daily living. The prevalence of cognitive impairment in multiple sclerosis varies across the lifespan and might be difficult to distinguish from other causes in older age. MRI studies show that widespread changes to brain networks contribute to cognitive dysfunction, and grey matter atrophy is an early sign of potential future cognitive decline. Neuropsychological research suggests that cognitive processing speed and episodic memory are the most frequently affected cognitive domains. Narrowing evaluation to these core areas permits brief, routine assessment in the clinical setting. Owing to its brevity, reliability, and sensitivity, the Symbol Digit Modalities Test, or its computer-based analogues, can be used to monitor episodes of acute disease activity. The Symbol Digit Modalities Test can also be used in clinical trials, and data increasingly show that cognitive processing speed and memory are amenable to cognitive training interventions.

Journal ArticleDOI
TL;DR: The findings reported in the last decade are starting to help to decipher the complex relations between plant polyphenols and cell homeostatic systems including metabolic and redox equilibrium, proteostasis, and the inflammatory response, establishing an increasingly solid molecular basis for the healthy effects of these molecules.
Abstract: The increasing extension in life expectancy of human beings in developed countries is accompanied by a progressively greater rate of degenerative diseases associated with lifestyle and aging, most of which are still waiting for effective, not merely symptomatic, therapies. Accordingly, at present, the recommendations aimed at reducing the prevalence of these conditions in the population are limited to a safer lifestyle including physical/mental exercise, a reduced caloric intake, and a proper diet in a convivial environment. The claimed health benefits of the Mediterranean and Asian diets have been confirmed in many clinical trials and epidemiological surveys. These diets are characterized by several features, including low meat consumption, the intake of oils instead of fats as lipid sources, moderate amounts of red wine, and significant amounts of fresh fruit and vegetables. In particular, the latter have attracted popular and scientific attention for their content, though in reduced amounts, of a number of molecules increasingly investigated for their healthy properties. Among the latter, plant polyphenols have raised remarkable interest in the scientific community; in fact, several clinical trials have confirmed that many health benefits of the Mediterranean/Asian diets can be traced back to the presence of significant amounts of these molecules, even though, in some cases, contradictory results have been reported, which highlights the need for further investigation. In light of the results of these trials, recent research has sought to provide information on the biochemical, molecular, epigenetic, and cell biology modifications by plant polyphenols in cell, organismal, animal, and human models of cancer, metabolic, and neurodegenerative pathologies, notably Alzheimer’s and Parkinson disease. The findings reported in the last decade are starting to help to decipher the complex relations between plant polyphenols and cell homeostatic systems including metabolic and redox equilibrium, proteostasis, and the inflammatory response, establishing an increasingly solid molecular basis for the healthy effects of these molecules. Taken together, the data currently available, though still incomplete, are providing a rationale for the possible use of natural polyphenols, or their molecular scaffolds, as nutraceuticals to contrast aging and to combat many associated pathologies.

Journal ArticleDOI
TL;DR: In this paper, the authors present a four-stage crisis management model (calamity, quick and dirty, restart, and adapt), which provides insights and critical actions that should be taken to cope with the expected short and long-term implications of the crisis.

Journal ArticleDOI
TL;DR: In this article, the authors presented the results of the second workshop on ASEAN Regional Climate Data, Analysis and Projections (ARCDAP•2), which was held at the University of Singapore and was jointly funded by Meteorological Service Singapore and WMO through the Canada Climate Risk and Early Warning Systems (CREWS) initiative.
Abstract: Robert Dunn was supported by the Met Office Hadley Centre Climate Programme funded by BEIS and Defra (GA01101) and thanks Nick Rayner and Lizzie Good for helpful comments on the manuscript Lisa Alexander is supported by the Australian Research Council (ARC) Grants DP160103439 and CE170100023 Markus Donat acknowledges funding by the Spanish Ministry for the Economy, Industry and Competitiveness Ramon y Cajal 2017 Grant Reference RYC‐2017‐22964 Mohd Noor'Arifin Bin Hj Yussof and Muhammad Khairul Izzat Bin Ibrahim thank the Brunei Darussalam Meteorological Department (BDMD) Ying Sun was supported by China funding agencies 2018YFA0605604 and 2018YFC1507702 Fatemeh Rahimzadeh and Mahbobeh Khoshkam thank IR of Iranian Meteorological Organization (IRIMO) and the Atmospheric Science and Meteorological Organization Research Center (ASMERC) for Data and also sharing their experiences, especially Abbas Rangbar Jose Marengo was supported by the National Institute of Science and Technology for Climate Change Phase 2 under CNPq Grant 465501/2014‐1, FAPESP Grants 2014/50848‐9 and 2015/03804‐9, and the National Coordination for High Level Education and Training (CAPES) Grant 88887136402‐00INCT The team that worked on the data in West Africa received funding from the UK's National Environment Research Council (NERC)/Department for International Development DFID) Future Climate For Africa programme, under the AMMA‐2050 project (Grants NE/M020428/1 and NE/M019969/1) Data from Southeast Asia (excl Indonesia) was supported by work on using ClimPACT2 during the Second Workshop on ASEAN Regional Climate Data, Analysis and Projections (ARCDAP‐2), 25–29 March 2019, Singapore, jointly funded by Meteorological Service Singapore and WMO through the Canada‐Climate Risk and Early Warning Systems (CREWS) initiative This research was supported by Thai Meteorological Department (TMD) and Thailand Science Research and Innovation (TSRI) under Grant RDG6030003 Daily data for Mexico were provided by the Servicio Meteorologico Nacional (SMN) of Comision Nacional del Agua (CONAGUA) We acknowledge the data providers in the ECA&D project (https://wwwecadeu), the SACA&D project (https://saca-bmkgknminl), and the LACA&D project (https://ciifenknminl) We thank the three anonymous reviewers for their detailed comments which improved the manuscript

Journal ArticleDOI
Juliette Alimena1, James Baker Beacham2, Martino Borsato3, Yangyang Cheng4  +213 moreInstitutions (105)
TL;DR: In this paper, the authors present a survey of the current state of LLP searches at the Large Hadron Collider (LHC) and chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC.
Abstract: Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton–proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments—as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER—to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.

Journal ArticleDOI
TL;DR: An easy to access and quick tool was chosen by the investigators in order to permit the other colleagues to spend the least amount of time, given the severe health emergency.
Abstract: We have recently noticed an outbreak of chilblain-like lesions in Italy contemporarily to COVID-19 epidemic. Due to the well known lockdown-related difficulties to visit the patients1 we created a Google form aimed to collect information about patients presenting with these singular clinical findings. An easy to access and quick tool was chosen by the investigators in order to permit the other colleagues to spend the least amount of time, given the severe health emergency.

Journal ArticleDOI
TL;DR: A review of the literature on digital servitization can be found in this paper, where a case-based approach is used to investigate the role of digital technologies for intermediate and advanced services in industrial equipment, automotive, and IT industries.