Author: "Thomas J. Evans" - Searchworks@Jio Institute Digital Library Search Results

179 results on '"Thomas J. Evans"'

1. Genomic Analysis of Global Staphylococcus argenteus Strains Reveals Distinct Lineages With Differing Virulence and Antibiotic Resistance Gene Content

Author: Cosmika Goswami, Stephen Fox, Matthew Holden, Alistair Leanord, and Thomas J. Evans
Subjects: Staphylococcus argenteus pathogenicity islands, Staphylococcus argenteus, antibiotic resistance, virulence genes, CRISPR/Cas, Microbiology, QR1-502
Abstract: Infections due to Staphylococcus argenteus have been increasingly reported worldwide and the microbe cannot be distinguished from Staphylococcus aureus by standard methods. Its complement of virulence determinants and antibiotic resistance genes remain unclear, and how far these are distinct from those produced by S. aureus remains undetermined. In order to address these uncertainties, we have collected 132 publicly available sequences from fourteen different countries, including the United Kingdom, between 2005 and 2018 to study the global genetic structure of the population. We have compared the genomes for antibiotic resistance genes, virulence determinants and mobile genetic elements such as phages, pathogenicity islands and presence of plasmid groups between different clades. 20% (n = 26) isolates were methicillin resistant harboring a mecA gene and 88% were penicillin resistant, harboring the blaZ gene. ST2250 was identified as the most frequent strain, but ST1223, which was the second largest group, contained a marginally larger number of virulence genes compared to the other STs. Novel S. argenteus pathogenicity islands were identified in our isolates harboring tsst-1, seb, sec3, ear, selk, selq toxin genes, as well as chromosomal clusters of enterotoxin and superantigen-like genes. Strain-specific type I modification systems were widespread which would limit interstrain transfer of genetic material. In addition, ST2250 possessed a CRISPR/Cas system, lacking in most other STs. S. argenteus possesses important genetic differences from S. aureus, as well as between different STs, with the potential to produce distinct clinical manifestations.
Published: 2021
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2. A Longitudinal Study of the Human Oropharynx Microbiota Over Time Reveals a Common Core and Significant Variations With Self-Reported Disease

Author: Lydia Luise Bach, Asha Ram, Umer Z. Ijaz, Thomas J. Evans, and Jan Lindström
Subjects: microbiome, core, oropharynx, oral, microbial, community, Microbiology, QR1-502
Abstract: Our understanding of human microbial communities, in particular in regard to diseases is advancing, yet the basic understanding of the microbiome in healthy subjects over time remains limited. The oropharynx is a key target for colonization by several important human pathogens. To understand how the oropharyngeal microbiome might limit infections, and how intercurrent infections might be associated with its composition, we characterized the oropharyngeal microbiome of 18 healthy adults, sampled weekly over a 40-weeks using culture-independent molecular techniques. We detected nine phyla, 202 genera and 1438 assignments on OTU level, dominated by Firmicutes, Bacteroidetes, and Proteobacteria on phylum level. Individual microbiomes of participants were characterized by levels of high alpha diversity (mean = 204.55 OTUs, sd = 35.64), evenness (19.83, sd = 9.74) and high temporal stability (mean Pearson’s correlation between samples of 0.52, sd = 0.060), with greater differences in microbiome community composition between than within individuals. Significant changes in community composition were associated with disease states, suggesting that it is possible to detect specific changes in OTU abundance and community composition during illness. We defined the common core microbiota by varying occurrence and abundance thresholds showing that individual core microbiomes share a substantial number of OTUs across participants, chiefly Streptococci and Veillonella. Our results provide insights into the microbial communities that characterize the healthy human oropharynx, community structure and variability, and provide new approaches to define individual and shared cores. The wider implications of this result include the potential for modeling the general dynamics of oropharynx microbiota both in health and in response to antimicrobial treatments or probiotics.
Published: 2021
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3. The Effects of Smoking on Human Pharynx Microbiota Composition and Stability

Author: Lydia Bach, Asha Ram, Umer Z. Ijaz, Thomas J. Evans, Daniel T. Haydon, and Jan Lindström
Subjects: Microbiology (medical), Infectious Diseases, General Immunology and Microbiology, Ecology, Physiology, Genetics, Cell Biology
Abstract: Smoking is associated with an increased risk of respiratory infections. Hypothetically, the altered community diversity of smokers’ pharyngeal microbiota, together with changes in their ecological stability properties, could facilitate their invasion by pathogens.
Published: 2023
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4. Consideration of within-patient diversity highlights transmission pathways and antimicrobial resistance gene variability in vancomycin resistantEnterococcus faecium

Author: Martin P McHugh, Kerry A Pettigrew, Surabhi Taori, Thomas J Evans, Alistair Leanord, Stephen H Gillespie, Kate E Templeton, and Matthew TG Holden
Abstract: SynopsisBackgroundWhole genome sequencing (WGS) is increasingly applied to healthcare-associated vancomycin-resistantEnterococcus faecium(VREfm) outbreaks. Within-patient diversity could complicate transmission resolution if single colonies are sequenced from identified cases.ObjectivesDetermine the impact of within-patient diversity on transmission resolution of VREfmMethodsFourteen colonies were collected from VREfm positive rectal screens, single colonies were collected from clinical samples, and Illumina WGS performed. Two isolates were selected for Oxford Nanopore sequencing and hybrid genome assembly to generate lineage-specific reference genomes. Mapping to closely related references was used to identify genetic variations and closely related genomes. A transmission network was inferred for the entire genome set using Phyloscanner.ResultsIn total, 229 isolates from 11 patients were sequenced. Carriage of 2-3 sequence types was detected in 27% of patients. Presence of antimicrobial resistance genes and plasmids was variable within genomes from the same patient and sequence type. We identified two dominant sequence types (ST80 and ST1424), with two putative transmission clusters of two patients within ST80, and a single cluster of six patients within ST1424. We found transmission resolution was impaired using fewer than 14 colonies.ConclusionsPatients can carry multiple sequence types of VREfm, and even within related lineages the presence of mobile genetic elements and antimicrobial resistance genes can vary. VREfm within-patient diversity should be considered to ensure accurate resolution of transmission networks.
Published: 2022
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5. A mechanistic framework to inform the spatial management of conflicting fisheries and top predators

Author: Thomas J. Evans, Olof Olsson, Jonas Hentati-Sundberg, Natalie Isaksson, Per-Arvid Berglund, and Agnes B. Olin
Subjects: 0106 biological sciences, Marine conservation, Fish and Wildlife Management, Ecology, biology, 010604 marine biology & hydrobiology, Foraging, Sprat, Marine spatial planning, biology.organism_classification, 010603 evolutionary biology, 01 natural sciences, Ecosystem-based management, Fishery, Forage fish, Fisheries management, QA, Apex predator
Abstract: Conflicts of interest between resource extraction and conservation are widespread, and negotiating such conflicts, or trade-offs, is a key issue for ecosystem managers. One such trade-off is resource competition between fisheries and marine top predators. Managing this trade-off has so far been difficult due to a lack of knowledge regarding the amount and distribution of prey required by top predators. Here, we develop a framework that can be used to address this gap: a bio-energetic model linking top predator breeding biology and foraging ecology with forage fish ecology and fisheries management. We apply the framework to a Baltic Sea colony of common guillemots Uria aalge and razorbills Alca torda, two seabird species sensitive to local prey depletion, and show that densities of forage fish (sprat Sprattus sprattus and herring Clupea harengus) corresponding to the current fisheries management target BMSY are sufficient for successful breeding. A previously proposed fisheries management target for conserving seabirds, 1/3 of historical maximum prey biomass (B1/3), was also sufficient. However, the results highlight the importance of maintaining sufficient prey densities in the vicinity of the colony, suggesting that fine-scale spatial fisheries management is necessary to maintain high seabird breeding success. Despite foraging on the same prey, razorbills could breed successfully at lower prey densities than guillemots but needed higher densities for self-maintenance, emphasizing the importance of considering species-specific traits when determining sustainable forage fish densities for top predators. Synthesis and applications. Our bio-energetic modelling framework provides spatially explicit top predator conservation targets that can be readily integrated with current fisheries management. The framework can be combined with existing management approaches such as dynamic ocean management, marine spatial planning and management strategy evaluation to inform ecosystem-based management of marine resources.
Published: 2020
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6. Safe laboratory management of prions and proteopathic seeds

Author: Simon Mead and Thomas J. Evans
Subjects: medicine.medical_specialty, business.industry, Laboratory management, Alzheimer Disease, Prions, MEDLINE, Medicine, Humans, tau Proteins, Neurology (clinical), business, Intensive care medicine
Published: 2021

7. Pyocin efficacy in a murine model of Pseudomonas aeruginosa sepsis

Author: Madhuri Barge, Daniel Walker, Colin Kleanthous, Anne Six, Thomas J. Evans, and Khedidja Mosbahi
Subjects: 0301 basic medicine, Microbiology (medical), medicine.drug_class, 030106 microbiology, Antibiotics, medicine.disease_cause, Microbiology, Sepsis, Mice, 03 medical and health sciences, Antibiotic resistance, In vivo, Animals, AcademicSubjects/MED00740, Medicine, Pseudomonas Infections, Pharmacology (medical), Original Research, 030304 developmental biology, Pharmacology, Pyocins, 0303 health sciences, biology, 030306 microbiology, business.industry, Pseudomonas aeruginosa, Biological activity, biology.organism_classification, Antimicrobial, medicine.disease, In vitro, 3. Good health, Galleria mellonella, Disease Models, Animal, AcademicSubjects/MED00290, 030104 developmental biology, Infectious Diseases, AcademicSubjects/MED00230, business
Abstract: Background Bloodstream infections with antibiotic-resistant Pseudomonas aeruginosa are common and increasingly difficult to treat. Pyocins are naturally occurring protein antibiotics produced by P. aeruginosa that have potential for human use. Objectives To determine if pyocin treatment is effective in a murine model of sepsis with P. aeruginosa. Methods Recombinant pyocins S5 and AP41 were purified and tested for efficacy in a Galleria mellonella infection model and a murine model of P. aeruginosa sepsis. Results Both pyocins produced no adverse effects when injected alone into mice and showed good in vitro antipseudomonal activity. In an invertebrate model of sepsis using G. mellonella, both pyocins significantly prolonged survival from 1/10 (10%) survival in controls to 80%–100% survival among groups of 10 pyocin-treated larvae. Following injection into mice, both showed extensive distribution into different organs. When administered 5 h after infection, pyocin S5 significantly increased survival from 33% (2/6) to 83% (5/6) in a murine model of sepsis (difference significant by log-rank test, P Conclusions Pyocins S5 and AP41 show in vivo biological activity and can improve survival in two models of P. aeruginosa infection. They hold promise as novel antimicrobial agents for treatment of MDR infections with this microbe.
Published: 2021

8. Assessment of Risks of Dioxins for Aryl Hydrocarbon Receptor-Mediated Effects in Polar Bear (Ursus maritimus) by in Vitro and in Silico Approaches

Author: Thomas J. Evans, Ji-Hee Hwang, Kurunthachalam Kannan, Eun-Young Kim, and Hisato Iwata
Subjects: biology, Chemistry, Ursus maritimus, In silico, Aryl, General Chemistry, 010501 environmental sciences, Aryl hydrocarbon receptor, 01 natural sciences, In vitro, chemistry.chemical_compound, Environmental chemistry, biology.animal, biology.protein, Environmental Chemistry, 0105 earth and related environmental sciences
Abstract: Polar bear (Ursus maritimus) populations accumulate dioxins and related compounds (DRCs) at levels that are of health concern. The toxicities of DRCs are primarily mediated via aryl hydrocarbon rec...
Published: 2019
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9. Optimal central place foraging flights in relation to wind

Author: Johan Bäckman, Thomas Alerstam, and Thomas J. Evans
Subjects: 0106 biological sciences, Low altitude, Wind gradient, Meteorology, Foraging, Terrain, Effects of high altitude on humans, 010603 evolutionary biology, 01 natural sciences, Wind speed, 010605 ornithology, Optimal foraging theory, Environmental science, Crosswind
Abstract: Many flying animals, like birds feeding their young, make commuting flights between a central place and foraging areas in the surroundings. Such central place foraging (CPF) represents a special case of foraging theory. We use simple geometry and trigonometry to analyse CPF flight performance (a round-trip cycle of outward flight from the central place and inward flight back along the reverse track) in relation to wind. In addition to considering the situation of a constant and uniform wind field, we take into account two factors that are likely to apply in many CPF situations under natural conditions: (a) that animals carry a load that will increase the energy expenditure during the inward flight and (b) that they may fly at different altitudes during out- and inward flights in the wind gradient above the ground or sea surface. Four main predictions emerge: (1) efficiency of CPF flights will be reduced with increasing wind speed, and foraging at the longest ranges is expected under low wind speeds. (2) A preference for CPF flights in crosswinds is expected in a constant and uniform wind field. (3) Carrying a load during the inward flight makes it optimal to fly with a small component of following winds during this flight while the outward flight will have a corresponding component of opposed winds. (4) With a steep wind gradient (e.g. over rough terrain) providing much shelter from wind at the lowest altitudes, predicted behaviour may change from crosswind preference to a preference for flights along the head/tailwind axis (at low altitude into headwinds and high altitude in tailwinds). Detailed tests of predictions for CPF flights in relation to wind will be important for understanding constraints and adaptations in animal responses to wind and for evaluating consequences of changing wind regimes in animal movement ecology.
Published: 2019
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10. Boosting BCG with proteins or rAd5 does not enhance protection against tuberculosis in rhesus macaques

Author: Charles A. Scanga, Mario Roederer, JoAnne L. Flynn, Mark Rodgers, Pauline Maiello, Joshua A Hackney, Thomas Lindenstrøm, Amy J. Myers, Victor Prikhodko, Dominick Laddy, Hannah P. Gideon, Patricia A. Darrah, Philana Ling Lin, Robert M. DiFazio, Peter Andersen, Thomas J. Evans, and Robert A. Seder
Subjects: lcsh:Immunologic diseases. Allergy, Tuberculosis, medicine.medical_treatment, Immunology, Heterologous, Diseases, Microbiology, complex mixtures, lcsh:RC254-282, Article, Mycobacterium tuberculosis, 03 medical and health sciences, 0302 clinical medicine, Antigen, Immunity, medicine, Pharmacology (medical), 030304 developmental biology, Pharmacology, 0303 health sciences, medicine.diagnostic_test, biology, business.industry, biology.organism_classification, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Infectious Diseases, Bronchoalveolar lavage, business, lcsh:RC581-607, Adjuvant, CD8, 030215 immunology
Abstract: Tuberculosis (TB) is the leading cause of death from infection worldwide. The only approved vaccine, BCG, has variable protective efficacy against pulmonary TB, the transmissible form of the disease. Therefore, improving this efficacy is an urgent priority. This study assessed whether heterologous prime-boost vaccine regimens in which BCG priming is boosted with either (i) protein and adjuvant (M72 plus AS01E or H56 plus CAF01) delivered intramuscularly (IM), or (ii) replication-defective recombinant adenovirus serotype 5 (Ad5) expressing various Mycobacterium tuberculosis (Mtb) antigens (Ad5(TB): M72, ESAT-6/Ag85b, or ESAT-6/Rv1733/Rv2626/RpfD) administered simultaneously by IM and aerosol (AE) routes, could enhance blood- and lung-localized T-cell immunity and improve protection in a nonhuman primate (NHP) model of TB infection. Ad5(TB) vaccines administered by AE/IM routes following BCG priming elicited ~10–30% antigen-specific CD4 and CD8 T-cell multifunctional cytokine responses in bronchoalveolar lavage (BAL) but did not provide additional protection compared to BCG alone. Moreover, AE administration of an Ad5(empty) control vector after BCG priming appeared to diminish protection induced by BCG. Boosting BCG by IM immunization of M72/AS01E or H56:CAF01 elicited ~0.1–0.3% antigen-specific CD4 cytokine responses in blood with only a transient increase of ~0.5–1% in BAL; these vaccine regimens also failed to enhance BCG-induced protection. Taken together, this study shows that boosting BCG with protein/adjuvant or Ad-based vaccines using these antigens, by IM or IM/AE routes, respectively, do not enhance protection against primary infection compared with BCG alone, in the highly susceptible rhesus macaque model of tuberculosis., Tuberculosis vaccination: Multi-platform/route BCG boosting in rhesus macaques BCG is the only clinically-approved tuberculosis (TB) vaccine but has highly variable protection against pulmonary manifestations of the disease. JoAnne Flynn and colleagues at the University of Pittsburgh investigate whether heterologous boosting can improve the efficacy of BCG vaccination in a highly susceptible rhesus macaque model. The boosting is performed using a variety of vaccination routes (intramuscular, aerosol) and platforms including multiple Mycobacterium tuberculosis (Mtb) protein subunits in adjuvant and/or expressed in adenovirus vectors. The various platforms and routes are designed to enhance immune responses thought to be involved in protection from Mtb. Despite in certain cases (e.g., aerosol) being able to enhance lung T cell cytokine responses, none of the boosting regimens showed any improved protection over standard intradermal BCG vaccination. This study highlights the formidable challenges facing attempts to elicit robust pulmonary protection against pulmonary Mtb infection.
Published: 2019
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11. Postexposure prophylaxis with rVSV-ZEBOV following exposure to a patient with Ebola virus disease relapse in the United Kingdom: an operational, safety, and immunogenicity report

Author: Rory Gunson, Beth White, Erica Peters, Kate Templeton, Celia Jackson, Elizabeth Spence, Catie Sykes, Ana Maria Henao Restrepo, Yper Hall, Susan Bennett, Maria Zambon, Stephan Becker, Marie Paule Kieny, Miles W. Carroll, Jim McMenamin, Thomas J. Evans, Thomas Strecker, Celia Aitken, E. Thomson, Suleman R. Sabir, Fiona Thorburn, Sarah Katharina Fehling, Ingolfur Johanssen, Chris Davis, and Tom Tipton
Subjects: 0301 basic medicine, Microbiology (medical), myalgia, medicine.medical_specialty, rVSV-ZEBOV, medicine.medical_treatment, Vesicular stomatitis Indiana virus, medicine.disease_cause, Antibodies, Viral, Virus, 03 medical and health sciences, Ebola virus, 0302 clinical medicine, Recurrence, Internal medicine, vaccine, medicine, Humans, 030212 general & internal medicine, Post-exposure prophylaxis, Ebola Vaccines, Adverse effect, business.industry, T cell, Hemorrhagic Fever, Ebola, Ebolavirus, United Kingdom, Vaccination, Major Articles and Commentaries, 030104 developmental biology, Infectious Diseases, AcademicSubjects/MED00290, Expanded access, medicine.symptom, business, Post-Exposure Prophylaxis, Follow-Up Studies
Abstract: Background In October 2015, 65 people came into direct contact with a healthcare worker presenting with a late reactivation of Ebola virus disease (EVD) in the United Kingdom. Vaccination was offered to 45 individuals with an initial assessment of high exposure risk. Methods Approval for rapid expanded access to the recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV) vaccine as an unlicensed emergency medicine was obtained from the relevant authorities. An observational follow-up study was carried out for 1 year following vaccination. Results Twenty-six of 45 individuals elected to receive vaccination between 10 and 11 October 2015 following written informed consent. By day 14, 39% had seroconverted, increasing to 87% by day 28 and 100% by 3 months, although these responses were not always sustained. Neutralizing antibody responses were detectable in 36% by day 14 and 73% at 12 months. Common side effects included fatigue, myalgia, headache, arthralgia, and fever. These were positively associated with glycoprotein-specific T-cell but not immunoglobulin (Ig) M or IgG antibody responses. No severe vaccine-related adverse events were reported. No one exposed to the virus became infected. Conclusions This paper reports the use of the rVSV-ZEBOV vaccine given as an emergency intervention to individuals exposed to a patient presenting with a late reactivation of EVD. The vaccine was relatively well tolerated, but a high percentage developed a fever ≥37.5°C, necessitating urgent screening for Ebola virus, and a small number developed persistent arthralgia., The rVSV-ZEBOV vaccine was used as postexposure prophylaxis in individuals exposed to Ebola virus in the United Kingdom. It was rolled out rapidly and was generally well tolerated. Side effects correlated with the magnitude of CD8+ T-cell responses.
Published: 2020

12. Atypical presentations in the hospitalised older adult testing positive for SARS-CoV-2: a retrospective observational study in Glasgow, Scotland

Author: Amy Bryan, Ren Ping Lee, Steven Wishart, Thomas J. Evans, Jamie Ingram, Lara Mitchell, Emily Cecilia Wright, Eileen Capek, Elizabeth Burleigh, Jon Godwin, Peter G Davis, and Rory Gibson
Subjects: Male, Pediatrics, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Frail Elderly, older people, 03 medical and health sciences, 0302 clinical medicine, COVID-19 Testing, delirium, prognostic indicators, Pandemic, Medicine, Humans, 030212 general & internal medicine, Aged, Retrospective Studies, Aged, 80 and over, Cross Infection, Frailty, business.industry, Mortality rate, Nosocomial transmission, Age Factors, COVID-19, Retrospective cohort study, General Medicine, Middle Aged, Prognosis, Scotland, Delirium, Female, Original Article, medicine.symptom, Severe Acute Respiratory Syndrome Coronavirus 2, Coronavirus Disease 2019, business, Older people, 030217 neurology & neurosurgery
Abstract: Introduction: Understanding of how SARS-CoV-2 manifests itself in older adults was unknown at the outset of the pandemic. We undertook a retrospective observational analysis of all patients admitted to older people’s services with confirmed COVID-19 in one of the largest hospitals in Europe. We detail presenting symptoms, prognostic features and vulnerability to nosocomial spread. Methods: We retrospectively collected data for each patient with a positive SARSCoV-2 RT PCR between 18th March and the 20th April 2020 in a department of medicine for the elderly in Glasgow. Results: 222 patients were included in our analysis. Age ranged from 56 to 99 years (mean = 82) and 148 were female (67%). 119 patients had a positive swab for SARS-CoV-2 within the first 14 days of admission, only 32% of these patients presented with primarily a respiratory type illness. 103 patients (46%) tested positive after 14 days of admission – this was felt to represent likely nosocomial infection. 95 patients (43%) died by day 30 after diagnosis. Discussion: This data indicates that older people were more likely to present with non-respiratory symptoms. High clinical frailty scores, severe lymphopenia and cumulative comorbidities were associated with higher mortality rates. Several contributing factors will have led to nosocomial transmission.
Published: 2020

13. P21 Novel ex-vivo model of septic arthritis identifies role of neutrophils in joint destruction and identifies a potential biomarker for diagnosis

Author: Carl S. Goodyear, Christian Thudium, Caroline Atherton, Iain B. McInnes, Thomas J. Evans, Kathryn Mccall, and Neal L. Millar
Subjects: Joint destruction, business.industry, Joint infections, medicine.disease, Rheumatology, Potential biomarkers, Immunology, Bacterial arthritis, Medicine, Coculture Technique, Pharmacology (medical), Septic arthritis, business, Cartilage damage, Ex vivo
Abstract: Background Septic arthritis (SA) caused by bacterial species, such as Staphylococcus aureus, has high morbidity and mortality. Currently diagnosis is often prolonged and unreliable, with no suitable near-patient biomarkers available. To generate more reliable biomarkers and to understand pathogenesis we sought to develop a novel ex vivo system to explore the effect of pathogenic Staph. aureus strains in promoting cartilage degradation. Methods Human cartilage explants were obtained from femoral heads being surgically removed following trauma. Explants were infected for 48h with 106 cfu bacteria from two Staph. aureus SA-derived patient isolates (28g & 36v strains). In the final 24h of bacterial infection, neutrophils purified from healthy donor blood were added to explant cultures at 3 x 106 cells/well. Chondrocyte viability was assessed using CellTracker green CMFDA and propidium iodide. Images were captured using confocal microscopy (LSM880) and cells counted using Imaris software. Structural damage was measured by glycosaminoglycan (GAG) and a neo-epitope of MMP-mediated degradation of type II collagen (C2M) release. Statistical analysis was performed using GraphPad Prism software. Results When cartilage explants were co-cultured with bacteria +/- neutrophils, cell death was significantly increased compared to the negative control or addition of neutrophils alone, (Friedman multiple comparisons test, N = 3, negative control vs. bacteria - neutrophils p Conclusion A co-culture model of septic arthritis has been developed which allows precise examination of the contribution of the host neutrophil response to cartilage damage. We used this to identify a collagen breakdown product as a biomarker of host response to infected cartilage. This novel model will be a valuable tool in understanding the pathology of joint infection and can be used for the identification of future diagnostic biomarkers. Disclosures K.E. McCall None. C. Atherton None. C. Thudium None. C. Goodyear Grants/research support; C.G. has received funding for research from Celgene, AstraZeneca, MedAnnex, UCB & Jannsen. T. Evans None. N. Millar Grants/research support; Novartis. I. McInnes Consultancies; I.M. has received consultancies fees from BMS, Abbvie, Lilly, GSK & Pfizer. Grants/research support; I.M received research funding from Calgene, Janssen, Novartis, Boehringer Ingelheim & BMS.
Published: 2020
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14. Origin, maintenance and spread of antibiotic resistance genes within plasmids and chromosomes of bloodstream isolates of Escherichia coli

Author: Martin Connor, Alistair Leanord, Stephen Fox, Matthew T. G. Holden, Thomas J. Evans, Cosmika Goswami, University of St Andrews. School of Medicine, University of St Andrews. Biomedical Sciences Research Complex, University of St Andrews. Infection and Global Health Division, and University of St Andrews. Infection Group
Subjects: Gene Transfer, Horizontal, medicine.drug_class, Antibiotics, Bacteremia, Biology, Extended spectrum beta-lactamases, medicine.disease_cause, Microbial evolution and epidemiology: Communicable disease genomics, Antibiotic resistance, Plasmid, SDG 3 - Good Health and Well-being, Sepsis, Drug Resistance, Bacterial, Escherichia coli, medicine, Humans, QR180 Immunology, bacteremia, Gene, Escherichia coli Infections, Phylogeny, Genetics, Whole Genome Sequencing, Escherichia coli Proteins, Chromosome, DAS, General Medicine, Horizontal gene transfer, Chromosomes, Bacterial, United Kingdom, extended spectrum beta-lactamases, QR180, Trimethoprim Resistance, horizontal gene transfer, Research Article, Plasmids
Abstract: The work was funded by the Scottish Executive via the Chief Scientists Office through the provision of a grant to establish the Scottish Healthcare Associated Infection Prevention Institute (SHAIPI). Blood stream invasion by Escherichia coli is the commonest cause of bacteremia in the UK and elsewhere with an attributable mortality of about 15–20 %; antibiotic resistance to multiple agents is common in this microbe and is associated with worse outcomes. Genes conferring antimicrobial resistance, and their frequent location on horizontally transferred genetic elements is well-recognised, but the origin of these determinants, and their ability to be maintained and spread within clinically-relevant bacterial populations is unclear. Here, we set out to examine the distribution of antimicrobial resistance genes in chromosomes and plasmids of 16 bloodstream isolates of E. coli from patients within Scotland, and how these genes are maintained and spread. Using a combination of short and long-read whole genome sequencing methods, we were able to assemble complete sequences of 44 plasmids, with 16 Inc group F and 20 col plasmids; antibiotic resistance genes located almost exclusively within the F group. blaCTX-M15 genes had re-arranged in some strains into the chromosome alone (five strains), while others contained plasmid copies alone (two strains). Integrons containing multiple antibiotic genes were widespread in plasmids, notably many with a dfrA7 gene encoding resistance to trimethoprim, thus linking trimethoprim resistance to the other antibiotic resistance genes within the plasmids. This will allow even narrow spectrum antibiotics such as trimethoprim to act as a selective agent for plasmids containing antibiotic resistance genes mediating much broader resistance, including blaCTX-M15. To our knowledge, this is the first analysis to provide complete sequence data of chromosomes and plasmids in a collection of pathogenic human bloodstream isolates of E. coli. Our findings reveal the interplay between plasmids and integrative and conjugative elements in the maintenance and spread of antibiotic resistance genes within pathogenic E. coli. Publisher PDF
Published: 2020

15. A highly conserved complete accessory Escherichia coli type III secretion system 2 is widespread in bloodstream isolates of the ST69 lineage

Author: Andrew J. Roe, Matthew T. G. Holden, Martin Connor, Cosmika Goswami, James P. R. Connolly, Stephen Fox, Nicky O’Boyle, James Mordue, Thomas J. Evans, Alistair Leanord, University of St Andrews. School of Medicine, University of St Andrews. Biomedical Sciences Research Complex, University of St Andrews. Infection and Global Health Division, and University of St Andrews. Infection Group
Subjects: 0301 basic medicine, 030106 microbiology, lcsh:Medicine, Locus (genetics), QH426 Genetics, Biology, medicine.disease_cause, Genome, Article, Bacterial genetics, Type three secretion system, 03 medical and health sciences, Genetics research, medicine, Type III Secretion Systems, Humans, lcsh:Science, Escherichia coli, Gene, QH426, Escherichia coli Infections, Genetics, Reporter gene, Multidisciplinary, Effector, Escherichia coli Proteins, lcsh:R, DAS, Gene Expression Regulation, Bacterial, QR Microbiology, QR, 030104 developmental biology, RB Pathology, Mutation, lcsh:Q, RB
Abstract: The work was funded by the Scottish Executive via the Chief Scientists Office through the provision of a grant to establish the Scottish Healthcare Associated Infection Prevention Institute (SHAIPI). The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication. Bacterial type III secretion systems (T3SSs) play an important role in pathogenesis of Gram-negative infections. Enteropathogenic and enterohemorrhagic Escherichia coli contain a well-defined T3SS but in addition a second T3SS termed E. coli T3SS 2 (ETT2) has been described in a number of strains of E. coli. The majority of pathogenic E. coli contain elements of a genetic locus encoding ETT2, but which has undergone significant mutational attrition rendering it without predicted function. Only a very few strains have been reported to contain an intact ETT2 locus. To investigate the occurrence of the ETT2 locus in strains of human pathogenic E. coli, we carried out genomic sequencing of 162 isolates obtained from patient blood cultures in Scotland. We found that 22 of 26 sequence type (ST) 69 isolates from this collection contained an intact ETT2 together with an associated eip locus which encodes putative secreted ETT2 effectors as well as eilA, a gene encoding a putative transcriptional regulator of ETT2 associated genes. Using a reporter gene for eilA activation, we defined conditions under which this gene was differentially activated. Analysis of published E. coli genomes with worldwide representation showed that ST69 contained an intact ETT2 in these strains as well. The conservation of the genes encoding ETT2 in human pathogenic ST69 strains strongly suggests it has importance in infection, although its exact functional role remains obscure. Publisher PDF
Published: 2020

16. Lenvatinib and its use in the treatment of unresectable hepatocellular carcinoma

Author: Hilary Glen, Thomas J. Evans, and Mark Baxter
Subjects: Sorafenib, Oncology, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, medicine.drug_class, Drug Evaluation, Preclinical, Antineoplastic Agents, Tyrosine-kinase inhibitor, Multikinase inhibitor, Inhibitory Concentration 50, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Biomarkers, Tumor, medicine, Carcinoma, Animals, Humans, In patient, 030212 general & internal medicine, Protein Kinase Inhibitors, Neoplasm Staging, Clinical Trials as Topic, business.industry, Phenylurea Compounds, Liver Neoplasms, General Medicine, medicine.disease, digestive system diseases, Drug development, chemistry, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Quinolines, Lenvatinib, business, medicine.drug
Abstract: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver accounting for approximately 90% of cases. Patients often present at an advanced stage when treatment options are limited. Sorafenib, a multitargeted tyrosine kinase inhibitor, has been the first-line treatment in this setting for almost a decade. Several subsequent targeted therapies have failed to demonstrate significant improvement in survival. The results of the REFLECT study suggest that lenvatinib, a multikinase inhibitor, may have promised as a first-line treatment in patients with advanced HCC. This article will review the development of lenvatinib and the evidence behind its potential use in patients with advanced HCC.
Published: 2018
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17. Stochastic Pharmacokinetic-Pharmacodynamic Modeling for Assessing the Systemic Health Risk of Perfluorooctanoate (PFOA)

Author: Iain R. Macpherson, Leslie Samuel, Eddie Doyle, Yang Liu, Matteo Convertino, Anna Barnett, Clifford R. Elcombe, Geary W. Olsen, Thomas J. Evans, and Timothy R. Church
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Thyroid Gland, Antineoplastic Agents, 010501 environmental sciences, Toxicology, Models, Biological, 01 natural sciences, thyroid, Pbpk Modeling for Pfoa Risk, 03 medical and health sciences, chemistry.chemical_compound, phase 1 trial, Liver Function Tests, Pharmacokinetics, Thyroid-stimulating hormone, Neoplasms, Internal medicine, medicine, Humans, Generalized estimating equation, 0105 earth and related environmental sciences, Fluorocarbons, Dose-Response Relationship, Drug, Cholesterol, PFOA, cholesterol, Middle Aged, Orders of magnitude (mass), Thyroxine, APFO, Dose–response relationship, Treatment Outcome, 030104 developmental biology, Endocrinology, Liver, chemistry, Pharmacodynamics, Female, PK/PD modeling, Caprylates, Lipoprotein
Abstract: A phase 1 dose-escalation trial assessed the chemotherapeutic potential of ammonium perfluorooctanoate (APFO). Forty-nine primarily solid-tumor cancer patients who failed standard therapy received weekly APFO doses (50–1200 mg) for 6 weeks. Clinical chemistries and plasma PFOA (anionic APFO) were measured predose and weekly thereafter. Several clinical measures including total cholesterol, high-density lipoproteins (HDLs), thyroid stimulating hormone (TSH), and free thyroxine (fT4), relative to PFOA concentrations were examined by: Standard statistical analyses using generalized estimating equations (GEE) and a probabilistic analysis using probability distribution functions (pdf) at various PFOA concentrations; and a 2-compartment pharmacokinetic/pharmacodynamic (PK/PD) model to directly estimate mean changes. Based on the GEE, the average rates of change in total cholesterol and fT4 associated with increasing PFOA were approximately −1.2×10−3 mmol/l/μM and 2.8×10−3 pmol/l/μM, respectively. The PK/PD model predicted more closely the trends observed in the data as well as the pdfs of biomarkers. A decline in total cholesterol was observed, with a clear transition in shape and range of the pdfs, manifested by the maximum value of the Kullback-Leibler (KL) divergence, that occurred at plasma PFOA between 420 and 565 μM (175 000–230 000 ng/ml). High-density lipoprotein was unchanged. An increase in fT4 was observed at a higher PFOA transition point, albeit TSH was unchanged. Our findings are consistent with some animal models and may motivate re-examination of the epidemiologic studies to PFOA at levels several orders of magnitude lower than this study. These observational studies have reported contrary associations, but currently understood biology does not support the existence of such conflicting effects.
Published: 2018
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18. Immune checkpoint inhibitors: new strategies to checkmate cancer

Author: Alasdair R. Fraser, Ruairi A. M. Wilson, Robert J. B. Nibbs, and Thomas J. Evans
Subjects: 0301 basic medicine, T cell, Immune checkpoint inhibitors, Programmed Cell Death 1 Receptor, Immunology, Cancer therapy, Antineoplastic Agents, Review Article, Biology, Malignant disease, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, medicine, Animals, Humans, Immunology and Allergy, CTLA-4 Antigen, Pharmaceutical sciences, Clinical Trials as Topic, Antibodies, Monoclonal, Cancer, medicine.disease, Combined Modality Therapy, Clinical trial, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunotherapy, Tumor immunology
Abstract: Summary Immune checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte-associated protein-4 (CTLA-4) or programmed cell death protein 1 (PD-1) receptors have demonstrated remarkable efficacy in subsets of patients with malignant disease. This emerging treatment modality holds great promise for future cancer treatment and has engaged pharmaceutical research interests in tumour immunology. While ICIs can induce rapid and durable responses in some patients, identifying predictive factors for effective clinical responses has proved challenging. This review summarizes the mechanisms of action of ICIs and outlines important preclinical work that contributed to their development. We explore clinical data that has led to disease-specific drug licensing, and highlight key clinical trials that have revealed ICI efficacy across a range of malignancies. We describe how ICIs have been used as part of combination therapies, and explore their future prospects in this area. We conclude by discussing the incorporation of these new immunotherapeutics into precision approaches to cancer therapy.
Published: 2017
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19. Assessment of Risks of Dioxins for Aryl Hydrocarbon Receptor-Mediated Effects in Polar Bear (

Author: Ji-Hee, Hwang, Kurunthachalam, Kannan, Thomas J, Evans, Hisato, Iwata, and Eun-Young, Kim
Subjects: Mice, Mice, Inbred C3H, Receptors, Aryl Hydrocarbon, Animals, Computer Simulation, Dioxins, Ursidae
Abstract: Polar bear (
Published: 2019

20. Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial

Author: Thomas J. Evans, Jean Pierre Delord, Ibrahima Soumaoro, Junchen Gu, Bin Li, Ana Oaknin, Suzanne L. Topalian, Ricardo Zwirtes, Tim Meyer, Kathleen N. Moore, Tian Chen, José María López-Picazo, Joseph Kerger, Michael John Devlin, R. Wendel Naumann, Valentina Boni, Jean-Pascal Machiels, Antoine Hollebecque, Emiliano Calvo, Institut Català de la Salut, [Naumann RW] Levine Cancer Institute, Atrium Health, Charlotte, NC. [Hollebecque A] Gustave Roussy, Villejuif, France. [Meyer T, Devlin MJ] UCL Cancer Institute, London, United Kingdom. [Oaknin A] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Kerger J] Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium, Vall d'Hebron Barcelona Hospital Campus, and Hospital Universitari Vall d'Hebron
Subjects: 0301 basic medicine, Oncology, Adult, Cancer Research, medicine.medical_specialty, Time Factors, Vaginal Neoplasms, neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales femeninos [ENFERMEDADES], Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female [DISEASES], Checkmate, Uterine Cervical Neoplasms, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Medicaments antineoplàstics, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Agents, Immunological, Internal medicine, medicine, Humans, In patient, Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression [DISEASES], Progression-free survival, Neoplasm Metastasis, Papillomaviridae, Aged, Vulvar Neoplasms, business.industry, Aparell genital femení - Càncer, ORIGINAL REPORTS, Middle Aged, Progression-Free Survival, United States, Clinical trial, Europe, afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::progresión de la enfermedad [ENFERMEDADES], 030104 developmental biology, Phase i ii, Nivolumab, Multicenter study, 030220 oncology & carcinogenesis, Disease Progression, Female, Vulvar Carcinoma, Neoplasm Recurrence, Local, business, Gynecological Cancer
Abstract: Nivolumab; Carcinoma cervical, vaginal o vulvar; Carcinoma metastàtic Nivolumab; Cervical, vaginal, or vulvar carcinoma; Metastatic carcinoma Nivolumab; Carcinoma de cuello uterino, vaginal o vulvar; Carcinoma metastático PURPOSE Nivolumab was assessed in patients with virus-associated tumors in the phase I/II CheckMate 358 trial (ClinicalTrials.gov identifier: NCT02488759). We report on patients with recurrent/metastatic cervical, vaginal, or vulvar cancers. PATIENTS AND METHODS Patients received nivolumab 240 mg every 2 weeks. Although patients with unknown human papillomavirus status were enrolled, patients known to have human papillomavirus–negative tumors were ineligible. The primary end point was objective response rate. Duration of response (DOR), progression-free survival, and overall survival were secondary end points. Safety and patient-reported outcomes were exploratory end points. RESULTS Twenty-four patients (cervical, n = 19; vaginal/vulvar, n = 5) were enrolled. Most patients had received prior systemic therapy for metastatic disease (cervical, 78.9%; vaginal/vulvar, 80.0%). Objective response rates were 26.3% (95% CI, 9.1 to 51.2) for cervical cancer and 20.0% (95% CI, 0.5 to 71.6) for vaginal/vulvar cancers. At a median follow-up of 19.2 months, median DOR was not reached (range, 23.3 to 29.5+ months; + indicates a censored observation) in the five responding patients in the cervical cohort; the DOR was 5.0 months in the single responding patient in the vaginal/vulvar cohort. Median overall survival was 21.9 months (95% CI, 15.1 months to not reached) among patients with cervical cancer. Any-grade treatment-related adverse events were reported in 12 of 19 patients (63.2%) in the cervical cohort and all five patients in the vaginal/vulvar cohort; there were no treatment-related deaths. In the cervical cohort, nivolumab treatment generally resulted in stabilization of patient-reported outcomes associated with health status and health-related quality of life. CONCLUSION The efficacy of nivolumab in patients with recurrent/metastatic cervical and vaginal or vulvar cancers is promising and warrants additional investigation. No new safety signals were identified with nivolumab treatment in this population.
Published: 2019

21. Optic flow cues help explain altitude control over sea in freely flying gulls

Author: Susanne Åkesson, Anders Hedenström, Franck Ruffier, Judy Shamoun-Baranes, Julien Serres, Olivier Duriez, Thomas J. Evans, Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Departement of Biology, CAnMove, Lund University, Lund University [Lund], Marine Scotland Science (MSS), Université Paul-Valéry - Montpellier 3 (UPVM), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Theoretical and Computational Ecology, Institute of Biodiversity and Ecosystem Dynamics, University of Amsterdam, Centre National de la Recherche Scientifique (CNRS), Swedish Research Council (621-2007-5930, 621-2010-5584, 621-2013-4361, 621-2012-3585), Lund University, a Linnaeus grant from the Swedish Research Council (349-2007-8690) to the Centre for Animal Movement Research (CAnMove) Lund University., Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Department of Biology, CAnMove, Lund University, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Université Paul-Valéry - Montpellier 3 (UPVM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut de Recherche pour le Développement (IRD [France-Sud]), Marine Scotland Science, Marine Laboratory, Université Paul Valéry (Montpellier 3), Université Paul-Valéry - Montpellier 3 (UM3)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Theoretical and Computational Ecology (IBED, FNWI)
Subjects: 0106 biological sciences, energy invariant, Oceans and Seas, Flow (psychology), Biomedical Engineering, Biophysics, Bioengineering, 010603 evolutionary biology, 01 natural sciences, Biochemistry, Models, Biological, optical invariant, [SPI.AUTO]Engineering Sciences [physics]/Automatic, Biomaterials, 03 medical and health sciences, Charadriiformes, Altitude, Range (aeronautics), Animals, flight modelling, 14. Life underwater, Takeoff, Sensory cue, Rate of climb, Vision, Ocular, 030304 developmental biology, 0303 health sciences, biology, [SCCO.NEUR]Cognitive science/Neuroscience, Elevation, Life Sciences–Physics interface, biology.organism_classification, Geodesy, motion vision, Flight, Animal, Environmental science, visual, Larus fuscus, visual neuroscience, Biotechnology
Abstract: For studies of how birds control their altitude, seabirds are of particular interest because they forage offshore where the visual environment can be simply modelled by a flat world textured by waves then generating only ventral visual cues. This study suggests that optic flow, i.e. the rate at which the sea moves across the eye’s retina, can explain gulls’ altitude control over seas. In particular, a new flight model that includes both energy and optical invariants helps explain the gulls’ trajectories during offshore takeoff and cruising flight. A linear mixed model applied to 352 flights from 16 individual lesser black backed gulls (Larus fuscus) revealed a statistically significant optic flow set-point ofca25° s−1. Thereafter, an optic flow-based flight model was applied to 18 offshore takeoff flights from nine individual gulls. By introducing an upper limit in climb rate on the elevation dynamics, coupled with an optic flow set-point, the predicted altitude gives an optimized fit factor value of 63% on average (30–83% in range) with respect to the GPS data. We conclude that the optic flow regulation principle helps gulls to adjust their altitude over sea without having to directly measure their current altitude.
Published: 2019
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22. Dual RNA-seq in <named-content content-type='genus-species'>Streptococcus pneumoniae</named-content> Infection Reveals Compartmentalized Neutrophil Responses in Lung and Pleural Space

Author: Neil D. Ritchie and Thomas J. Evans
Subjects: Physiology, Virulence, Biology, medicine.disease_cause, Biochemistry, Microbiology, Host-Microbe Biology, Transcriptome, 03 medical and health sciences, Pleural disease, transcriptomics, neutrophils, Streptococcus pneumoniae, Genetics, medicine, pneumonia, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, Neutrophil extravasation, dual RNA-seq, 030302 biochemistry & molecular biology, RNA, respiratory system, medicine.disease, biology.organism_classification, Editor's Pick, QR1-502, 3. Good health, Computer Science Applications, respiratory tract diseases, Bacterial adhesin, Modeling and Simulation, Bacteria, Research Article
Abstract: The factors that regulate the passage of bacteria between different anatomical compartments are unclear. We have used an experimental model of infection with Streptococcus pneumoniae to examine the host and bacterial factors involved in the passage of bacteria from the lung to the pleural space. The transcriptional profile of host and bacterial cells within the pleural space and lung was analyzed using deep sequencing of the entire transcriptome using the technique of dual RNA-seq. We found significant differences in the host and bacterial RNA profiles in infection, which shed light on the key factors that allow passage of this bacterium into the pleural space., Streptococcus pneumoniae is the dominant cause of community-acquired pneumonia worldwide. Invasion of the pleural space is common and results in increased mortality. We set out to determine the bacterial and host factors that influence invasion of the pleural space. In a murine model of pneumococcal infection, we isolated neutrophil-dominated samples of bronchoalveolar and pleural fluid containing bacteria 48 hours after infection. Using dual RNA sequencing (RNA-seq), we characterized bacterial and host transcripts that were differentially regulated between these compartments and bacteria in broth and resting neutrophils, respectively. Pleural and lung samples showed upregulation of genes involved in the positive regulation of neutrophil extravasation but downregulation of genes mediating bacterial killing. Compared to the lung samples, cells within the pleural space showed marked upregulation of many genes induced by type I interferons, which are cytokines implicated in preventing bacterial transmigration across epithelial barriers. Differences in the bacterial transcripts between the infected samples and bacteria grown in broth showed the upregulation of genes in the bacteriocin locus, the pneumococcal surface adhesin PsaA, and the glycopeptide resistance gene vanZ; the gene encoding the ClpP protease was downregulated in infection. One hundred sixty-nine intergenic putative small bacterial RNAs were also identified, of which 43 (25.4%) small RNAs had been previously described. Forty-two of the small RNAs were upregulated in pleura compared to broth, including many previously identified as being important in virulence. Our results have identified key host and bacterial responses to invasion of the pleural space that can be potentially exploited to develop alternative antimicrobial strategies for the prevention and treatment of pneumococcal pleural disease. IMPORTANCE The factors that regulate the passage of bacteria between different anatomical compartments are unclear. We have used an experimental model of infection with Streptococcus pneumoniae to examine the host and bacterial factors involved in the passage of bacteria from the lung to the pleural space. The transcriptional profile of host and bacterial cells within the pleural space and lung was analyzed using deep sequencing of the entire transcriptome using the technique of dual RNA-seq. We found significant differences in the host and bacterial RNA profiles in infection, which shed light on the key factors that allow passage of this bacterium into the pleural space.
Published: 2019
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23. AB0097 NOVEL EX VIVOMODEL OF SEPTIC ARTHRITIS DEVELOPED TO IDENTIFY BIOMARKERS RELEASED UPON ARTICULAR INFECTION

Author: Carl S. Goodyear, Thomas J. Evans, Iain B. McInnes, Caroline Atherton, Kathryn Mccall, and Neal L. Millar
Subjects: business.industry, Immunology, Medicine, Septic arthritis, business, medicine.disease
Published: 2019
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24. SAT0696-HPR THE PREVALENCE OF SEPTIC ARTHRITIS AT A LARGE UNIVERSITY TEACHING HOSPITAL

Author: Yianni Joannidis, Neal L. Millar, Thomas J. Evans, Iain B. McInnes, Kathryn Mccall, and Caroline Atherton
Subjects: medicine.medical_specialty, business.industry, Incidence (epidemiology), medicine.disease, Rheumatology, medicine.anatomical_structure, Internal medicine, Joint damage, medicine, Upper limb, Synovial fluid, Case note, Septic arthritis, University teaching, business
Abstract: Background: Septic arthritis (SA) is a rheumatological emergency requiring early treatment to prevent lasting joint damage. Treatment outcomes depend on prompt diagnosis, which currently rests on clinical suspicison, riased non-specifc inflammaotry markers and identification of a pathogen from synovial fluid. Objectives: To establish the prevalence of SA in a large University teaching hospital. To review the microbiology results and identified pathogens in each positive case along with subsequent treatment regimes utilising outpatinet parenteral antimicrobial therapy (OPAT) with adherence to local guidelines. Methods: Retrospective data collection of all samples identified as synovial fluid or joint aspiration sent to microbiology lab between 1stJanuary 2016 and 31st December 2016. Electronic review of microbiology results to identify the causal pathogen and case notes to review treatment and outcomes. Results: There were 364 samples identified as joint aspirate or synovial fluid, 54 of these grew a pathogen. Positive aspirates from native joints totaled 35 in 31 patients. Twenty-three of these patients accounting for 25 of the positive samples were treated clinically as SA. Sub analysis of this group revealed Staph.aureus was the most commonly identified pathogen in 14 cases (56%). There were however 8 other pathogens identified in the 25 positive samples. Fifteen patients (65%) underwent a joint washout in theatre, 7 of these patients had multiple washouts. Duration of antibiotic therapy was 5 weeks in 8 cases; 13 cases had therapy for >5 weeks and 2 cases with SA in the upper limb had treatment for Conclusion: In line with known literature, staph.aureus was the most common pathogen1, however there were a number of other bacteria identified which needs to be taken into account when formulating local antimicrobial guidelines. Current literature reports surgical treatment as not superior to medical2, yet 65% of cases here under went joint lavage in theatre. This information will be used to inform local clinical practice, and, guide recruitment targets for a large multi-centre study collecting data and samples from patients presenting with a hot swollen joint, with the aim of identifying a specific biomarker for SA. References [1] Rutherford A I, Kleymann A, Ibrahim F, Galloway J. The increasing incidence of septic arthritis in England between 1998 and 2013. Rheumatology April 2016 55(1):i51-i52 [2] Ravindran V, Logan I, Bourke B E. Medical vs Surgical treatment for the native joint in septic arthritis: A 6 year, single UK academic centre experience. RheumatologyOct200948(10):1320-1322 Disclosure of Interests: Caroline Atherton: None declared, Kathryn McCall: None declared, Neal L Millar: None declared, Yianni Joannidis: None declared, Tom Evans: None declared, Iain McInnes Grant/research support from: AstraZeneca, Celgene, Compugen, Novartis, Roche, UCB Pharma, Consultant for: AbbVie, Celgene, Galvani, Lilly, Novartis, Pfizer, UCB Pharma
Published: 2019
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25. Optic flow helps explain gulls’ altitude control over seas

Author: Thomas J. Evans, Olivier Duriez, Susanne Åkesson, Judy Shamoun-Baranes, Franck Ruffier, Anders Hedenström, and Serres
Subjects: Current (stream), Altitude, biology, Meteorology, Flow (psychology), Elevation, Environmental science, Submarine pipeline, Takeoff, Larus fuscus, biology.organism_classification, Rate of climb
Abstract: For studies of how flying animals control their flight, seabirds are of particular interest to track with a biologger because they forage offshore where the visual environment can be simply modeled by a flat world textured by waves. This study suggests that optic flow can explain gull’s altitude control over seas. In particular, a new flight model that includes both energy and optical invariants (called theventral optic flow regulation) explain the dynamics of gulls’ altitude control during offshore takeoff and cruising flight. A linear statistical model applied to 352 flights from 16 individual lesser black backed gulls (Larus fuscus) gave a strong correlation between wind assistance and gulls’ altitude. Thereafter, an optic flow-based flight model was applied to 18 offshore takeoff flights from 1. individual gulls. By introducing an upper limit in climb rate in a non-linear first order parametric model on the gull’s elevation dynamics, coupled with an optic-flow set-point, the predicted altitude gives an optimized fit factor value of 63% on average (min value: 30%, max value: 83%) with respect to GPS data. We conclude that the optic-flow regulation principle (here running close to 25°/s) allows gulls to adjust their altitude over sea without having to directly measure their current altitude.
Published: 2019
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26. Do uropathogenic E. coli require changes before it can spread into the bloodstream?

Author: Thomas J. Evans, Alistair Leanord, Cosmika Goswami, and Stephen Fox
Subjects: Kidney, medicine.anatomical_structure, Plasmid, Urinary system, medicine, Multilocus sequence typing, General Materials Science, Single-nucleotide polymorphism, Urine, Sample collection, Biology, Insertion sequence, Microbiology
Abstract: Background Uropathogenic Eschericha coli are the leading cause of urinary tract infections (UTIs). The microbe can spread from bladder to kidney and finally to blood. We wished to determine whether genetic changes accompany the passage of these infections from urine to blood. Material/methods 12 paired urine and blood samples were collected from patients in Greater Glasgow and Clyde; the interval between sample collection time between pairs was less than 48 h. Whole genomic sequencing of these paired samples was performed using the Illumina MiSeq platform. De novoassembly of reads was carried out using Shovill assembler; whereas SNPs were identified using SMALT, VarScan and Gubbins tools. Results Urine and blood samples in each pair had the same MLST type. Surprisingly, however, there were multiple differences in the presence of plasmid genes, phage elements and insertion sequences within pairs, as well as numerous SNPs. For example, the mercury reductase merAgene and mercuric transport protein merPhave been acquired in a plasmid of a blood isolate compared to the contemporaneous urine sample. We also identified missense mutations in genes involved in several metabolic pathways in bloodstream isolates. Several of the observed gene deletions/insertions and SNPs were found in more than one of the paired blood and urine isolates. Conclusions The observed sequence differences between contemporaneous blood and urine isolates suggests that genomic differences accumulate within the urinary bladder prior to blood stream invasion. The observed blood stream variants may thus possess a selective advantage in invasion and/or survival within blood.
Published: 2019
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27. Phase I/II open label nonrandomized safety and efficacy study of the viral vectored ChAdOx1-MVA 5T4 immunotherapy in combination with PD-1 checkpoint blockade in intermediate-risk localized or locally advanced prostate cancer and advanced metastatic prostate cancer

Author: Clare Verrill, Silke Gillessen, Richard J. Bryant, L. Carter, James W.F. Catto, Armin Meier, Adrian V. S. Hill, Thomas J. Evans, Freddie C. Hamdy, Federica Cappuccini, Günter Schmidt, Mark Tuthill, Irina Redchenko, Andrew Protheroe, Emily Pollock, and Ian D. Poulton
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, medicine.medical_treatment, Locally advanced, Immunotherapy, medicine.disease, Blockade, Prostate cancer, Phase i ii, Internal medicine, medicine, Open label, business, Intermediate risk, Efficacy Study
Abstract: TPS3170 Background: Antigen-specific immunotherapy (Sipuleucel-T) is licenced for the treatment for castrate resistant prostate cancer, but has modest clinical efficacy and is complex to administer to patients. New therapeutic antigen-specific approaches are required to generate and sustain therapeutic immune responses against tumour specific antigens in men with early and advanced prostate cancer. We have previously reported immunogenicity and efficacy data of a novel viral vectored vaccines-based immunotherapy based on two replication-deficient viruses, chimpanzee adenovirus (ChAdOx1) and MVA, targeting an oncofetal self-antigen 5T4, administered as a single agent and in combination with anti-PD-1 in mouse tumour models. We tested this immunotherapy alone in a first-in-human trial, VANCE (NCT02390063), in intermediate risk prostate cancer patients. Based on encouraging safety and exceptional T cell immunogenicity of the VANCE study, the phase I/II trial, ADVANCE (NCT03815942) is being undertaken to test the immunotherapy safety and efficacy in combination with PD-1 blockade in intermediate risk disease and metastatic prostate cancer. Methods: Study design: ADVANCE, an open label non-randomised phase I/II study, will recruit 12 patients with intermediate-risk prostate cancer patients (Gleason score ≤ 7, local tumour stage ≤T3c, PSA≤ 20 ng/ml) scheduled to undergo radical prostatectomy (Cohort 1) and 24 mCRPC patients with disease progression on anti-androgen therapy with either enzalutamide or abiraterone (Cohort 2). Cohort 1 will receive one cycle of ChAdOx1-MVA 5T4 immunotherapy and a single nivolumab infusion. Cohort 2 will receive 2 cycles of ChAdOx1-MVA 5T4 vaccination and three nivolumab infusions. Primary endpoint: Cohort 1 - PSA change from baseline to surgery, Cohort 2 – composite response rate measured as either ≥50% reduction of circulating tumour DNA or ≥50% serum PSA decrease from baseline at 24-week assessment and the maximal response rate. Secondary and exploratory endpoints include 5T4-specific immune response in the periphery, progression-free and overall survival and reduction of circulating tumour cells. 23 of planned 24 patients have been enrolled in Cohort 2. Enrolment to the Cohort 1 is ongoing. The data analysis is expected to be completed by Q4 2020 for Cohort 2. Clinical trial information: NCT03815942 .
Published: 2020
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28. Current state of knowledge on biological effects from contaminants on arctic wildlife and fish

Author: Colleen E. Bryan, Mary Gamberg, Katrin S. Hoydal, Emilie Andersen-Ranberg, Sabrina Tartu, Robert J. Letcher, Paul F. Hoekstra, Gabriele Treu, Pat Roach, Collin A. Eagles-Smith, Kathrine Eggers Pedersen, Anders Bignert, Lisa L. Loseto, Simon Wilson, Elizabeth Peacock, Derek C. G. Muir, Jennifer F. Provencher, Anders Mosbech, Mark L. Mallory, Birgit M. Braune, Jens Søndergaard, Gary A. Stern, Ane Haarr, Melissa A. McKinney, Aqqalu Rosing-Asvid, Erik W. Born, Tomasz Maciej Ciesielski, Jan Ove Bustnes, Robert T. Barrett, Milton Levin, Ketil Hylland, Benjamin D. Barst, Sarah H. Peterson, Igor Eulaers, Christian Sonne, Anuschka Polder, Stacy S. Schuur, Bjarne Styrishave, Kim Gustavson, Paul E. Drevnick, Marlene S. Evans, Rune Dietz, Bjørn Munro Jenssen, Janneche Utne Skaare, Cecilie Miljeteig, Halvor Saunes, Rasmus Dyrmose Nørregaard, Björn Helander, John R. Kucklick, Aaron T. Fisk, Garry B. Stenson, Joshua T. Ackerman, Allyson K. Jackson, Sanna Túni Nielsen, Jenny Bytingsvik, Frank Rigét, Magali Houde, Mark P. Herzog, Niladri Basu, Thomas J. Evans, Maria Dam, Jean-Pierre Desforges, C. Alex Hartman, Geir Wing Gabrielsen, Mikkel-Holger S. Sinding, Sara Pedro, Marsha Branigan, Gísli A. Víkingsson, Elisabeth Lie, and Jon Aars
Subjects: Environmental Engineering, 010504 meteorology & atmospheric sciences, Sentinel species, Population, Wildlife, Biological effects, Population health, 010501 environmental sciences, 01 natural sciences, Circumpolar Arctic, VDP::Agriculture and fishery disciplines: 900, biology.animal, VDP::Mathematics and natural science: 400::Zoology and botany: 480, Environmental Chemistry, Arctic fox, education, Waste Management and Disposal, 0105 earth and related environmental sciences, education.field_of_study, biology, VDP::Landbruks- og Fiskerifag: 900, Ecology, Cumulative effects, Biota, Mercury, Pollution, Fish, Arctic, geographic locations, VDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480, Organohalogen compounds
Abstract: Since the last Arctic Monitoring and Assessment Programme (AMAP) effort to review biological effects of the exposure to organohalogen compounds (OHCs) in Arctic biota, there has been a considerable number of new Arctic effect studies. Here, we provide an update on the state of the knowledge of OHC, and also include mercury, exposure and/or associated effects in key Arctic marine and terrestrial mammal and bird species as well as in fish by reviewing the literature published since the last AMAP assessment in 2010. We aimed at updating the knowledge of how single but also combined health effects are or can be associated to the exposure to single compounds or mixtures of OHCs. We also focussed on assessing both potential individual as well as population health impacts using population-specific exposure data post 2000. We have identified quantifiable effects on vitamin metabolism, immune functioning, thyroid and steroid hormone balances, oxidative stress, tissue pathology, and reproduction. As with the previous assessment, a wealth of documentation is available for biological effects in marine mammals and seabirds, and sentinel species such as the sledge dog and Arctic fox, but information for terrestrial vertebrates and fish remain scarce. While hormones and vitamins are thoroughly studied, oxidative stress, immunotoxic and reproductive effects need further investigation. Depending on the species and population, some OHCs and mercury tissue contaminant burdens post 2000 were observed to be high enough to exceed putative risk threshold levels that have been previously estimated for non-target species or populations outside the Arctic. In this assessment, we made use of risk quotient calculations to summarize the cumulative effects of different OHC classes and mercury for which critical body burdens can be estimated for wildlife across the Arctic. As our ultimate goal is to better predict or estimate the effects of OHCs and mercury in Arctic wildlife at the individual, population and ecosystem level, there remain numerous knowledge gaps on the biological effects of exposure in Arctic biota. These knowledge gaps include the establishment of concentration thresholds for individual compounds as well as for realistic cocktail mixtures that in fact indicate biologically relevant, and not statistically determined, health effects for specific species and subpopulations. Finally, we provide future perspectives on understanding Arctic wildlife health using new in vivo, in vitro, and in silico techniques, and provide case studies on multiple stressors to show that future assessments would benefit from significant efforts to integrate human health, wildlife ecology and retrospective and forecasting aspects into assessing the biological effects of OHC and mercury exposure in Arctic wildlife and fish. © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Published: 2019
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29. Foraging behaviour of Razorbills Alca torda during chick-rearing at the largest colony in the Baltic Sea

Author: Olof Olsson, Thomas J. Evans, Natalie Isaksson, and Susanne Åkesson
Subjects: 0106 biological sciences, Fishery, Geography, Baltic sea, Foraging, 010603 evolutionary biology, 01 natural sciences, Ecology, Evolution, Behavior and Systematics, 010605 ornithology, Nature and Landscape Conservation
Abstract: Capsule: Foraging behaviour in the Razorbill Alca torda during breeding was similar to that found elsewhere, aside from dive shape. Aims: To investigate the foraging behaviour of Razorbills during the breeding season at the largest colony in the central Baltic Sea. Methods: A combination of global positioning system (GPS) and time-depth recorder (TDR) devices were used on Razorbills breeding on the island of Stora Karlsö, Baltic Sea, during the chick-rearing period. Results: Five GPS tracks and nine TDR logs were retrieved from 12 Razorbills, and 7399 dives were analysed. Razorbills foraged south and southwest of the colony. Maximum and mean (±sd) foraging range from the colony was 72.7 km and 13.1 ± 13.5 km, respectively. Mean dive depth (15.3 ± 2.4 m) and duration (53.1 ± 8.5 s) were similar to those of a more southern Baltic Sea Razorbill colony. Dive depth had a bimodal distribution, with 70% of dives deeper than 10 m and 30% shallower than 10 m. There was a clear diel foraging pattern with 89% of dives occurring during daytime and a higher proportion of shallow dives at night. Unexpectedly, dives were primarily U-shaped. The Razorbills spent 31% of their overall time activity budget flying or diving. Conclusion: Aside from dive shape, foraging behaviour was consistent with that reported at other colonies of Razorbills. Inconsistency in dive shape may be due to a bimodal foraging strategy, local prey behaviour or competition with the Common Guillemot Uria aalge.
Published: 2019
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30. A highly conserved complete accessoryEscherichia colitype III secretion system 2 is widespread in bloodstream isolates of the ST69 lineage

Author: James P. R. Connolly, Stephen Fox, Matthew T. G. Holden, Martin Connor, Andrew J. Roe, Thomas J. Evans, Alistair Leanord, and Cosmika Goswami
Subjects: Genetics, Reporter gene, Effector, medicine, Transcriptional regulation, Locus (genetics), Secretion, Biology, medicine.disease_cause, Gene, Escherichia coli, Type three secretion system
Abstract: Bacterial type III secretion systems (T3SS) play an important role in pathogenesis of Gram-negative infections. Enteropathogenic and enterohemorrhagicEscherichia colicontain a well-defined T3SS but in addition a second T3SS termedE. coliT3SS 2 (ETT2) has been described in a number of strains ofE. coli.The majority ofE. colicontain elements of a genetic locus encoding ETT2, but which has undergone significant mutational attrition rendering it without predicted function. Only a very few strains have been reported to contain an intact ETT2 locus. To investigate the occurrence of the ETT2 locus in strains of human pathogenicE. coli, we carried out genomic sequencing of 162 isolates obtained from patient blood cultures in Scotland. We found that all 26 ST69 isolates from this collection contained an intact ETT2 together with an associatedeiplocus which encodes putative secreted ETT2 effectors as well aseilA, a gene encoding a putative transcriptional regulator of ETT2 associated genes. Using a reporter gene foreilAactivation, we defined conditions under which this gene was differentially activated. However, comparison of secreted proteins from ST69 strains under high and loweilAactivation failed to identify any ETT2 secreted substrates. The conservation of the genes encoding ETT2 in human pathogenic ST69 strains strongly suggests it has functional importance in infection, although its exact functional role remains obscure.ImportanceOne of the commonest bacteria causing bloodstream infections in humans isEscherichia coli, which has a significant morbidity and mortality. Better understating of the mechanisms by which this microbe can invade blood could lead to more effective prevention and treatment. One mechanism by which some strains cause disease is by elaboration of a specialized secretion system, the type III secretion system (T3SS), encoded by the locus of enterocyte effacement (LEE). In addition to this well-defined T3SS, a second T3SS has been found in someE. colistrains termedE. colitype III secretion system 2 (ETT2). Most strains carry elements of the ETT2 locus, but with significant mutational attrition rendering it functionless. The significance of our work is that we have discovered that human bloodstream isolates ofE. coliof sequence type 69 contain a fully intact ETT2 and associated genes, strongly suggesting its functional importance in human infection.
Published: 2018
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31. Genomic inversion drives small colony variant formation and increased virulence in P. aeruginosa

Author: Connolly Jpr, S. Irvine, Thomas J. Evans, Jörg Overmann, Sprӧer C, Daniel Walker, Andrew J. Roe, Hannah K. Bayes, Anne Six, and Boyke Bunk
Subjects: Genetics, 0303 health sciences, 030306 microbiology, Pseudomonas aeruginosa, Virulence, Biology, medicine.disease_cause, Phenotype, Genome, 03 medical and health sciences, Chronic infection, medicine, RRNA Operon, Gene, Illumina dye sequencing, 030304 developmental biology
Abstract: Phenotypic change is a hallmark of bacterial adaptation during chronic infection. In the case of chronicPseudomonas aeruginosalung infection in patients with cystic fibrosis, well-characterised phenotypic variants include mucoid and small colony variants (SCVs). It has previously been shown that SCVs can be reproducibly isolated from the murine lung following the establishment of chronic infection with mucoidP. aeruginosastrain NH57388A. Here we show, using a combination of singlemolecule real-time (PacBio) and Illumina sequencing that the genetic switch for conversion to the SCV phenotype is a large genomic inversion through recombination between homologous regions of two rRNA operons. This phenotypic conversion is associated with large-scale transcriptional changes distributed throughout the genome. This global rewiring of the cellular transcriptomic output results in changes to normally differentially regulated genes that modulate resistance to oxidative stress, central metabolism and virulence. These changes are of clinical relevance since the appearance of SCVs during chronic infection is associated with declining lung function.
Published: 2018
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32. Genetic analysis of invasive Escherichia coli in Scotland reveals determinants of healthcare-associated versus community-acquired infections

Author: Stephen Fox, Thomas J. Evans, Martin Connor, Alistair Leanord, Matthew T. G. Holden, Cosmika Goswami, University of St Andrews. School of Medicine, University of St Andrews. Infection and Global Health Division, University of St Andrews. Biomedical Sciences Research Complex, and University of St Andrews. Infection Group
Subjects: 0301 basic medicine, bacteraemia, Genome-wide association study, antibiotic resistance, Genotype, Antibiotic resistance, medicine.drug_class, Microbial Evolution and Epidemiology: Communicable Disease Genomics, 030106 microbiology, Antibiotics, Population, Virulence, Bacteremia, QH426 Genetics, Biology, Genome sequencing, Genetic analysis, 03 medical and health sciences, Plasmid, Escherichia coli, medicine, Humans, QR180 Immunology, education, QH426, Escherichia coli Infections, Genetics, Cross Infection, education.field_of_study, genome-wide association study, DAS, General Medicine, 3. Good health, genome sequencing, Community-Acquired Infections, 030104 developmental biology, Scotland, QR180, Bacteraemia, Research Article
Abstract: The work was funded by the Scottish Executive via the Chief Scientist Office through the provision of a grant to establish the Scottish Healthcare Associated Infection Prevention Institute (SHAIPI). Bacteraemia caused by Escherichia coli is a growing problem with a significant mortality. The factors that influence the acquisition and outcome of these infections are not clear. Here, we have linked detailed genetic data from the whole-genome sequencing of 162 bacteraemic isolates collected in Scotland, UK, in 2013-2015, with clinical data in order to delineate bacterial and host factors that influence the acquisition in hospital or the community, outcome and antibiotic resistance. We identified four major sequence types (STs) in these isolates: ST131, ST69, ST73 and ST95. Nearly 50% of the bacteraemic isolates had a urinary origin. ST69 was genetically distinct from the other STs, with significantly less sharing of accessory genes and with a distinct plasmid population. Virulence genes were widespread and diversely distributed between the dominant STs. ST131 was significantly associated with hospital-associated infections (HAIs), and ST69 with those from the community. However, there was no association of ST with outcome, although patients with HAI had a higher immediate mortality compared to those with community-associated infections (CAIs). Genome-wide association studies revealed genes involved in antibiotic persistence as significantly associated with HAIs and those encoding elements of a type VI secretion system with CAIs. Antibiotic resistance was common, and there were networks of correlated resistance genes and phenotypic antibiotic resistance. This study has revealed the complex interactions between the genotype of E. coli and its ability to cause bacteraemia, and some of the determinants influencing hospital or community acquisition. In part, these are shaped by antibiotic usage, but strain-specific factors are also important. Publisher PDF
Published: 2018
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33. IL-17 can be protective or deleterious in murine pneumococcal pneumonia

Author: Ryan Ritchie, Hannah K. Bayes, Neil D. Ritchie, Thomas J. Evans, and Timothy J. Mitchell
Subjects: 0301 basic medicine, Serotype, Pulmonology, Neutrophils, Physiology, medicine.medical_treatment, Bacteremia, medicine.disease_cause, Pathology and Laboratory Medicine, Biochemistry, White Blood Cells, Mice, Animal Cells, Immune Physiology, Nasopharynx, Medicine and Health Sciences, Biology (General), Lung, Mice, Knockout, Immune System Proteins, Receptors, Interleukin-17, biology, Interleukin-17, Receptors, Antigen, T-Cell, gamma-delta, Animal Models, Pneumococcus, 3. Good health, Body Fluids, Bacterial Pathogens, Specific Pathogen-Free Organisms, Cytokine, Blood, Streptococcus pneumoniae, Experimental Organism Systems, Medical Microbiology, Cell Processes, Pneumococcal pneumonia, Antibody, Cellular Types, Anatomy, Pathogens, Bronchoalveolar Lavage Fluid, Research Article, QH301-705.5, Immune Cells, Immunology, Mouse Models, Research and Analysis Methods, Microbiology, Antibodies, 03 medical and health sciences, Immune system, Model Organisms, Antigen, Phagocytosis, Microscopy, Electron, Transmission, Virology, Genetics, medicine, Animals, Molecular Biology, Microbial Pathogens, Bacterial Capsules, Peroxidase, Blood Cells, Bacteria, business.industry, Organisms, Biology and Life Sciences, Streptococcus, Proteins, Cell Biology, Pneumonia, Pneumonia, Pneumococcal, RC581-607, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Microscopy, Fluorescence, Respiratory Infections, biology.protein, Parasitology, Immunologic diseases. Allergy, business
Abstract: Streptococcus pneumoniae is the major bacterial cause of community-acquired pneumonia, and the leading agent of childhood pneumonia deaths worldwide. Nasal colonization is an essential step prior to infection. The cytokine IL-17 protects against such colonization and vaccines that enhance IL-17 responses to pneumococcal colonization are being developed. The role of IL-17 in host defence against pneumonia is not known. To address this issue, we have utilized a murine model of pneumococcal pneumonia in which the gene for the IL-17 cytokine family receptor, Il17ra, has been inactivated. Using this model, we show that IL-17 produced predominantly from γδ T cells protects mice against death from the invasive TIGR4 strain (serotype 4) which expresses a relatively thin capsule. However, in pneumonia produced by two heavily encapsulated strains with low invasive potential (serotypes 3 and 6B), IL-17 significantly enhanced mortality. Neutrophil uptake and killing of the serotype 3 strain was significantly impaired compared to the serotype 4 strain and depletion of neutrophils with antibody enhanced survival of mice infected with the highly encapsulated SRL1 strain. These data strongly suggest that IL-17 mediated neutrophil recruitment to the lungs clears infection from the invasive TIGR4 strain but that lung neutrophils exacerbate disease caused by the highly encapsulated pneumococcal strains. Thus, whilst augmenting IL-17 immune responses against pneumococci may decrease nasal colonization, this may worsen outcome during pneumonia caused by some strains., Author summary Streptococcus pneumoniae (the pneumococcus) is an important human pathogen and the commonest cause of community-acquired pneumonia. The bacterial carbohydrate capsule is a key determinant of virulence and host defence. Pneumonia follows colonization of the nasopharynx and can spread systemically. The cytokine IL-17, a key regulator of neutrophil host defence, is important in preventing colonization but its effects on pneumococcal pneumonia are not known. Here, we show that IL-17 has differing roles in host protection against pneumococcal pneumonia that depend on bacterial strain and capsule thickness. Pneumococci with thin capsules invade rapidly and IL-17 is protective; in strains with large capsules that remain in the lungs, IL-17 is detrimental. These strains evade neutrophil killing, and depletion of neutrophils improves outcome following infection. Thus, neutrophil accumulation within the lung is deleterious in pneumonia caused by heavily encapsulated pneumococcal strains. Our study provides fresh insight into the role of IL-17 in host defence against pneumococcal pneumonia, which may also be relevant in other infections caused by encapsulated bacteria that colonize before infection, such as the meningococcus and Haemophilus influenzae.
Published: 2018

34. Diagnosis and management of sepsis

Author: Thomas J. Evans
Subjects: medicine.medical_specialty, Resuscitation, Septic shock, business.industry, General Medicine, 030204 cardiovascular system & hematology, CME Infectious diseases, medicine.disease, Sepsis, Pathogenesis, 03 medical and health sciences, High morbidity, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Endothelial dysfunction, Intensive care medicine, business
Abstract: Sepsis is a common condition with high morbidity and mortality. Although many patients may require critical care, this article considers the features of sepsis that are of most relevance to acute general physicians. Recently updated definitions of sepsis and septic shock have been proposed which better identify patients who are likely to have a poor outcome, and therefore give an opportunity to escalate care. Despite these advances, there is still no molecular signature able to diagnose sepsis. Pathogenesis is complex, with many immune and non-immune mediators involved. Four key areas are endothelial dysfunction, coagulation abnormalities, alterations in cell function and dysregulated cardiovascular responses. No specific therapy targeting the mediators of sepsis has yet proven effective. Prompt administration of appropriate antibiotics is of benefit, together with fluid resuscitation and oxygen.
Published: 2018

35. Innovative clinical trial designs to rationalize TB vaccine development

Author: Dereck Tait, Willem A. Hanekom, Mark Hatherill, Ruth D. Ellis, Margaret A Snowden, Gavin J. Churchyard, Thomas J. Evans, and Ann M. Ginsberg
Subjects: Microbiology (medical), medicine.medical_specialty, Tuberculosis, Immunology, Disease, Target population, Microbiology, Recurrence, Risk Factors, Drug Discovery, medicine, Animals, Humans, Tuberculosis Vaccines, Intensive care medicine, Clinical Trials as Topic, business.industry, Patient Selection, medicine.disease, Clinical trial, Infectious Diseases, Research Design, Sample Size, Diffusion of Innovation, business
Abstract: A recent trial of a leading tuberculosis (TB) vaccine candidate in 3000 South African infants failed to show protection over that from BCG alone, and highlights the difficulties in clinical development of TB vaccines. Progression of vaccine candidates to efficacy trials against TB disease rests on demonstration of safety and immunogenicity in target populations and protection against challenge in preclinical models, but immunologic correlates of protection are unknown, and animal models may not be predictive of results in humans. Even in populations most heavily affected by TB the sample sizes required for Phase 2b efficacy trials using TB disease as an endpoint are in the thousands. Novel clinical trial models have been developed to evaluate candidate TB vaccines in selected populations using biologically relevant outcomes and innovative statistical approaches. Such proof of concept studies can be used to more rationally select vaccine candidates for advancement to large scale trials against TB disease.
Published: 2015
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36. Small colony variants of Pseudomonas aeruginosa in chronic bacterial infection of the lung in cystic fibrosis

Author: Thomas J. Evans
Subjects: Microbiology (medical), Cystic Fibrosis, Biology, medicine.disease_cause, Microbiology, Cystic fibrosis, Drug Resistance, Bacterial, medicine, Humans, Pseudomonas Infections, Cyclic GMP, Lung, Pathogen, Bronchiectasis, Pseudomonas aeruginosa, Genetic heterogeneity, Biofilm, medicine.disease, Anti-Bacterial Agents, Phenotype, medicine.anatomical_structure, Biofilms, Chronic Disease, Immunology, Sputum, medicine.symptom
Abstract: ABSTRACT Pseudomonas aeruginosa is the most common pathogen that colonizes the lungs of patients with cystic fibrosis. Isolates from sputum are typically all derived from the same strain of bacterium but show extensive phenotypic heterogeneity. One of these variants is the so-called small colony variant, which also shows increased ability to form a biofilm and is frequently resistant to multiple antibiotics. The presence of small colony variants in the sputum of patients with cystic fibrosis is associated with a worse clinical condition. The underlying mechanism responsible for generation of the small colony phenotype remains unclear, but a final common pathway would appear to be elevation of intracellular levels of cyclic di-GMP. This phenotypic variant is thus not just a laboratory curiosity, but a significant bacterial adaptation that favors survival within the lung of patients with cystic fibrosis and contributes to the pulmonary damage caused by P. aeruginosa.
Published: 2015
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37. IL-17 signalling restructures the nasal microbiome and drives dynamic changes following Streptococcus pneumoniae colonization

Author: Neil D. Ritchie, Umer Zeeshan Ijaz, and Thomas J. Evans
Subjects: 0301 basic medicine, Lung microbiome, lcsh:QH426-470, Firmicutes, lcsh:Biotechnology, 030106 microbiology, microbiome, Mucous membrane of nose, medicine.disease_cause, Ribotyping, Pneumococcal Infections, nasopharynx, Microbiology, Mice, 03 medical and health sciences, lcsh:TP248.13-248.65, Streptococcus pneumoniae, Genetics, medicine, Animals, Colonization, Microbiome, Lung, Mice, Knockout, Innate immunity, Receptors, Interleukin-17, biology, Microbiota, Interleukin-17, Human microbiome, Genetic Variation, biology.organism_classification, medicine.disease, Mice, Inbred C57BL, lcsh:Genetics, Nasal Mucosa, Pneumococcal infections, 030104 developmental biology, inflammation, Research Article, Biotechnology
Abstract: Background The bacterial pathogen Streptococcus pneumoniae colonizes the nasopharynx prior to causing disease, necessitating successful competition with the resident microflora. Cytokines of the IL-17 family are important in host defence against this pathogen but their effect on the nasopharyngeal microbiome is unknown. Here we analyse the influence of IL-17 on the composition and interactions of the nasopharyngeal microbiome before and after pneumococcal colonization. Results Using a murine model and 16S rRNA profiling, we found that a lack of IL-17 signalling led to profound alterations in the nasal but not lung microbiome characterized by decreased diversity and richness, increases in Proteobacteria and reduction in Bacteroidetes, Actinobacteria and Acidobacteria. Following experimental pneumococcal nasal inoculation, animals lacking IL-17 family signalling showed increased pneumococcal colonization, though both wild type and knockout animals showed as significant disruption of nasal microbiome composition, with increases in the proportion of Proteobacteria, even in animals that did not have persistent colonization. Sparse correlation analysis of the composition of the microbiome at various time points after infection showed strong positive interactions within the Firmicutes and Proteobacteria, but strong antagonism between members of these two phyla. Conclusions These results show the powerful influence of IL-17 signalling on the composition of the nasal microbiome before and after pneumococcal colonization, and apparent lack of interspecific competition between pneumococci and other Firmicutes. IL-17 driven changes in nasal microbiome composition may thus be an important factor in successful resistance to pneumococcal colonization and potentially could be manipulated to augment host defence against this pathogen. Electronic supplementary material The online version of this article (10.1186/s12864-017-4215-3) contains supplementary material, which is available to authorized users.
Published: 2017

38. The interrelationship between phagocytosis, autophagy and formation of neutrophil extracellular traps following infection of human neutrophils by Streptococcus pneumoniae

Author: Ihsan Ullah, Neil D. Ritchie, and Thomas J. Evans
Subjects: 0301 basic medicine, bacterial killing, Neutrophils, Phagocytosis, Immunology, ATG5, Biology, medicine.disease_cause, Extracellular Traps, Microbiology, Neutrophil Activation, Pneumococcal Infections, Autophagy-Related Protein 5, 03 medical and health sciences, Bacteriolysis, 0302 clinical medicine, Bacterial Proteins, stomatognathic system, Streptococcus pneumoniae, Autophagy, medicine, Humans, Molecular Biology, Cells, Cultured, neutrophil extracellular trap, Innate immune system, Pneumolysin, Original Articles, pneumolysin, Cell Biology, Neutrophil extracellular traps, respiratory system, medicine.disease, Immunity, Innate, 3. Good health, Pneumococcal infections, 030104 developmental biology, Infectious Diseases, Streptolysins, Reactive Oxygen Species, 030215 immunology
Abstract: Neutrophils play an important role in the innate immune response to infection with Streptococcus pneumoniae, the pneumococcus. Pneumococci are phagocytosed by neutrophils and undergo killing after ingestion. Other cellular processes may also be induced, including autophagy and the formation of neutrophil extracellular traps (NETs), which may play a role in bacterial eradication. We set out to determine how these different processes interacted following pneumococcal infection of neutrophils, and the role of the major pneumococcal toxin pneumolysin in these various pathways. We found that pneumococci induced autophagy in neutrophils in a type III phosphatidylinositol-3 kinase dependent fashion that also required the autophagy gene Atg5. Pneumolysin did not affect this process. Phagocytosis was inhibited by pneumolysin but enhanced by autophagy, while killing was accelerated by pneumolysin but inhibited by autophagy. Pneumococci induced extensive NET formation in neutrophils that was not influenced by pneumolysin but was critically dependent on autophagy. While pneumolysin did not affect NET formation, it had a potent inhibitory effect on bacterial trapping within NETs. These findings show a complex interaction between phagocytosis, killing, autophagy and NET formation in neutrophils following pneumococcal infection that contribute to host defence against this pathogen.
Published: 2017

39. Randomised controlled trial of azithromycin in smokers with asthma: Table 1–

Author: Mark Spears, Iona Donnelly, Frances S. Mair, Deborah Morrison, Neil C. Thomson, Nicola Greenlaw, Euan J. Cameron, Rekha Chaudhuri, Lisa Jolly, Katie Gallacher, K Anderson, Thomas J. Evans, Christopher J. Weir, and Charles McSharry
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Exacerbation, medicine.drug_class, business.industry, medicine.medical_treatment, medicine.disease, Placebo, Azithromycin, Anti-asthmatic Agent, respiratory tract diseases, Surgery, law.invention, Randomized controlled trial, law, Internal medicine, medicine, Corticosteroid, Lung transplantation, business, Asthma, medicine.drug
Abstract: To the Editor: Smokers with asthma have poor symptom control, accelerated decline in lung function and an attenuated response to corticosteroids compared to nonsmokers with asthma [1]. There is an unmet need for alternative or additional drugs for smokers with asthma who are unable to stop smoking [2]. Macrolide antibiotics have anti-inflammatory activity [3] and in clinical studies there is good evidence for efficacy in the treatment of diffuse pan-bronchiolitis and cystic fibrosis, as well as in preventing chronic rejection after lung transplantation [4, 5]. In asthma, chronic treatment is associated with a reduction in bronchial hyperreactivity in mild-to-moderate asthma [6] and in exacerbation rates in non-eosinophilic severe asthma [7]. To date, no studies have examined the efficacy of macrolide antibiotics exclusively in current smokers with asthma. A randomised double-blind parallel-group trial compared azithromycin, 250 mg per day, with placebo for 12 weeks. All subjects were aged 18–70 years, were current smokers (≥5 pack-years history) with chronic asthma (>1 year duration; defined by international criteria [8]) and had to be free of exacerbation and respiratory tract infection for a minimum 6-week period prior to randomisation. A baseline visit was performed following a 4-week run-in period on inhaled corticosteroid (ICS) therapy equivalent to 400 μg beclometasone ± a long-acting β2-agonist (LABA). Ethical approval was obtained and all subjects provided written informed consent. Study visits were performed at 4, 8 and 12 weeks. Clinic visit peak expiratory flow (PEF) after 12 weeks treatment was the primary outcome measure. A sample size of 68 …
Published: 2013
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40. Exploiting inflammation for therapeutic gain in pancreatic cancer

Author: Owen J. Sansom, Thomas J. Evans, Colin W. Steele, Jennifer P. Morton, C.R. Carter, Nigel B. Jamieson, and Colin J. McKay
Subjects: Cancer Research, Chemokine, endocrine system diseases, medicine.medical_treatment, pancreatic cancer, Inflammation, Malignancy, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Pancreatic cancer, Tumor Microenvironment, medicine, Animals, Humans, Molecular Targeted Therapy, Neoplasm Metastasis, Immunologic Surveillance, 030304 developmental biology, therapy, 0303 health sciences, Tumor microenvironment, biology, Macrophages, Prognosis, medicine.disease, digestive system diseases, 3. Good health, Pancreatic Neoplasms, Immunosurveillance, Cytokine, Oncology, 030220 oncology & carcinogenesis, Mutation, biology.protein, Cancer research, Cytokines, Tumor Escape, Minireview, Chemokines, medicine.symptom, Carcinoma, Pancreatic Ductal, Signal Transduction
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with
Published: 2013
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41. Adenovirally-Induced Polyfunctional T Cells Do Not Necessarily Recognize the Infected Target: Lessons from a Phase I Trial of the AERAS-402 Vaccine

Author: Lewellys F. Barker, Amanda Duncan, Jerald C. Sadoff, Maria Grazia Pau, Thomas J. Evans, Deborah A. Lewinsohn, Ervina Winata Huff, Gretta L Blatner, Melissa Nyendak, Macaya Douoguih, Meghan E. Cansler, David M. Lewinsohn, Gwendolyn Swarbrick, and David A. Hokey
Subjects: 0301 basic medicine, Serotype, Adult, CD4-Positive T-Lymphocytes, Male, T cell, Cell, CD8-Positive T-Lymphocytes, Article, Mycobacterium tuberculosis, 03 medical and health sciences, Young Adult, Immune system, Antigen, Double-Blind Method, medicine, Vaccines, DNA, Humans, Tuberculosis Vaccines, Multidisciplinary, biology, business.industry, Vaccination, biology.organism_classification, Virology, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Female, business, CD8
Abstract: The development of a vaccine for Mycobacterium tuberculosis (Mtb) has been impeded by the absence of correlates of protective immunity. One correlate would be the ability of cells induced by vaccination to recognize the Mtb-infected cell. AERAS-402 is a replication-deficient serotype 35 adenovirus containing DNA expressing a fusion protein of Mtb antigens 85A, 85B and TB10.4. We undertook a phase I double-blind, randomized placebo controlled trial of vaccination with AERAS-402 following BCG. Analysis of the vaccine-induced immune response revealed strong antigen-specific polyfunctional CD4+ and CD8+ T cell responses. However, analysis of the vaccine-induced CD8+ T cells revealed that in many instances these cells did not recognize the Mtb-infected cell. Our findings highlight the measurement of vaccine-induced, polyfunctional T cells may not reflect the extent or degree to which these cells are capable of identifying the Mtb-infected cell and correspondingly, the value of detailed experimental medicine studies early in vaccine development.
Published: 2016

42. Erratum

Author: Sascha Martens, Masashi Narita, Rajkumar Cheluvappa, Kevin A. Roth, Ta Yuan Chang, Kartik Venkatachalam, Chang-Shen Lin, Sharon G. Adler, Flaminia Pavone, Dianwen Ju, Michelle A. Ozbun, Michael R. Duchen, Shu Feng Zhou, Wei-Guo Zhu, Aaron Di Antonio, Defeng Wu, Taixing Cui, Xu Guang Guo, Zhiping Xie, Lorena García Nannig, Eloy Bejarano, Stéphane D. Lemaire, Petro Starokadomskyy, Hyung Ryong Kim, Mario Pinar, Rebecca T. Marquez, Zvenyslava Husak, Anthony R. White, Joanna Poulton, Antonis S. Zervos, Shweta Sharma, Jochen Walter, Nicholas T. Ktistakis, Christopher H.K. Cheng, Sunhee Lee, Yuen Li Chung, Howard O. Fearnhead, Young J. Oh, Ivano Amelio, Guillermo A. Blanco, Jan Simak, Junfang Wu, Yingying Lu, Mary Kate McBrayer, Soo Han Bae, Ichizo Nishino, Hong-Ming Hu, Benjamin R. Underwood, Tomonori Kimura, Zexian Liu, Savithrama P. Dinesh-Kumar, Qian Yang, Andreas Kern, Hsing Jien Kung, Jan B. Parys, Cam Patterson, Celine Perier, Toshiro Okazaki, Daisuke Koya, Avinash Sonawane, Cédric Cleyrat, Robert I. Richards, Kai Y. Soo, Rodrigo Mora-Rodriguez, Gigi N.C. Chiu, Moon Moo Kim, Vladimir N. Uversky, Shengfang Ge, Matthew T. V. Chan, Irene Kyrmizi, Lara Gibellini, Ángela M. Valverde, Erik Norberg, Fan Zhang, Jan C. Koch, Alec C. Kimmelman, Jingfang Ju, Jie Bai, Lei Duan, Paulina Ordonez, Shuwen Liu, Wolfdieter Springer, Eric Deutsch, Elena Ortona, Jose M. Seguí-Simarro, Vinay Choubey, Leonidas Stefanis, Robert G. Hawley, Claudia Bincoletto, Xian-Hui He, Zhifen Yang, Thomas M. Durcan, Martine Biard-Piechaczyk, Kui Lin, Hongming Pan, Konstantinos Kambas, Cristina Muñoz-Pinedo, Marta Magariños, Yoshinori Takahashi, Adrienne M. Gorman, Philippe Gailly, Takahiko Akematsu, Justine D. Mintern, Liang Xu, Tetsuo Shioi, Luis M. Botana, Yule Liu, Yong Yeon Cho, Jinzhi Lei, Eung Kweon Kim, Alakananda Basu, Vikash Kumar Dubey, Candelaria Gomez-Manzano, Avital Eisenberg-Lerner, Chuan-Ming Xie, Wenjie Dai, Pedro Gonzalez-Alegre, Maria Condello, Zheng-Hong Qin, Zhi-Min Yuan, Catherine Andreadi, Anna Rita Migliaccio, Chong Liu, Michaël Boyer-Guittaut, Melanie Denizot, Esperanza Arias, Greet Van den Berghe, Guomei Tang, Timothy P. Devarenne, Xianyong Sheng, Louis R. Lapierre, J. Wade Harper, Zuzana Storchova, Aileen R. Ariosa, Sug Hyung Lee, Qi Zeng, Godefridus J. Peters, Daniela L. Papademetrio, Alexandre Arcaro, Zhiyuan Yao, Pablo Iribarren, Mario Chiariello, Maria Rosaria Torrisi, Parimal Karmakar, Yong Huang, Sebastiano Sciarretta, Nathalie Andrieu-Abadie, László Fésüs, Patricia Boya, Ruediger Rudolf, Leonor Miller-Fleming, Vasilis J. Promponas, Juan Segura-Aguilar, Paula Daza, Shiow Ju Lee, Songshu Meng, Paul K. Herman, Ludwig Eichinger, Ye-Guang Chen, Kay F. Macleod, Thomas Simmet, Cristina Corral-Ramos, Claudio Brancolini, Jun Ren, Ying Jiang, Benoît Derrien, Xiao Fang Yu, Qing Zhong, Zong Wan Mao, Xingcong Ren, Armando A. Genazzani, Marina Pierdominici, Sanbing Shen, Sandra Moreno, Hana Algül, Maurizio Renna, Ricardo Sánchez-Prieto, Ashok K. Saluja, Yasuo Uchiyama, Pope L. Moseley, Victor E. Dosenko, Chun-Feng Liu, Bakhos A. Tannous, Efthimios Sivridis, Baharia Mograbi, Michiko Shintani, Amanda S. Bess, Rodrigo Portes Ureshino, Avnika A. Ruparelia, Paul Hofman, Eric Chevet, Martha M. Monick, Hong Gang Wang, Daping Fan, Jorge Moscat, Giuseppe Matarese, Consiglia Pacelli, Young Seok Cho, Miriam Cnop, Stefan Böckler, Nikolai V. Gorbunov, Christina J. Sigurdson, Hang T.T. Nguyen, Aurélie François, Katarina Kågedal, Sam Gandy, Silvia Campello, Alain Bruhat, Filomena Fiorito, Hua Feng, Man Tian Mi, Gian Maria Fimia, Masaki Tanaka, Guofei Zhou, José L. Crespo, Heinz Jungbluth, Anna Chiara Nascimbeni, Arianne L. Theiss, Svetlana Dokudovskaya, Mar Lorente, Sergio Lavandero, Yu Xia Zhao, Fangming Lin, Yuchen Feng, Gad Galili, Silvia Cetrullo, Paula I. Moreira, Dhyan Chandra, Dimitrios J. Stravopodis, Roberta A. Gottlieb, Gregory A. Taylor, Longping Wen, Faqiang Li, Marco Sardiello, Umesh K. Jinwal, Francesca Belleudi, Lan Tan, Livia Di Renzo, Tamas Korcsmaros, Xinbing Sui, Douglas R. Green, Guillermo Mazzolini, Hervé Le Stunff, Kelly S. Doran, Mary E. Choi, Carlos S. Subauste, Natalia Rodriguez-Muela, Nicholas J. Talbot, Marta Palmieri, Sonia Hernández-Tiedra, Ligia C. Gomes, Irving M. Shapiro, Makoto Ubukata, Mario P. Tschan, Baris Bingol, Benjamin Loos, Terry Kwok, Luca M. Neri, Sreejayan Nair, Michele Wolfe Bianchi, Ralf Erdmann, Alexander Greenhough, Neeraj Vij, Jeong Hun Kim, Satoaki Matoba, Bo Liu, George R. Beck, Michael Moore, Vrajesh V. Parekh, Kyle A. Bauckman, Li-Lin Du, Mikihiro Fujiya, Yan G. Zhao, Renaud Legouis, Jiangwei Zhang, Kailiang Jia, Nadezda Apostolova, Sehamuddin Galadari, Khosrow Adeli, Ming Yong Zhang, Carmela Fusco, Angel Ortega, Anna Pensalfini, Zsuzsanna Szatmári, Marco Tafani, Isabella Ceccherini, Anne Hamacher-Brady, Kuen Jer Tsai, Anita C. Truttmann, Franco Fortunato, Keisuke Miyazawa, Chunhai Fan, Berge A. Minassian, Jian Zhang, Frank A. Anania, Heesun Cheong, Amal O. Amer, Ing Swie Goping, Won-Ki Huh, Anita Solhaug, Joan Cl ria, Laurent Le Cam, Seungmin Hwang, Karen L. Wright, Antonella De Matteis, Troy T. Rohn, Ivana Bjedov, Subbiah Pugazhenthi, Hal E. Broxmeyer, Xue Yuan Bai, Koenraad Norga, Minnie M. Sarwal, Daniel F. Schorderet, Ioannis P. Nezis, Mei Qing Wang, Jun Hee Lee, Yong J. Lee, David A. Tumbarello, Fernando Macian, Joern Dengjel, Dmitry V. Bulavin, Andrew J. Halayko, Ben Berkhout, Aseem Pandey, Santosh Kesari, Karin Przyklenk, Elena V. Tchetina, Matthew L. Albert, Laura Segatori, Joel N. Meyer, Mustapha Rouis, Éva Margittai, Ashish Jain, David Hahn, Thomas Vaccari, Lori R. Covey, Ghanshyam Swarup, Kuo Yang Huang, Gennaro Napolitano, Sam W. Lee, Seong Who Kim, Alberto Anel, Vladimir V. Rogov, Laura A. Carleton, Amine Belaid, Byoung Kuk Jang, Sheng-Han Kuo, Patricia L. Yeyati, Jae U. Jung, Teresa Zoladek, Sabrina Di Bartolomeo, Clémence Richetta, Peixin Yang, Daniela Trisciuoglio, Hye Seung Jung, Katsumi Higaki, Eui-Bae Jeung, Ivan Topisirovic, Isabella Caniggia, Susan E. Logue, Issidora S. Papassideri, Lynda A. Morrison, Caihong Wang, Graeme Sargent, Beth Levine, Mingxiang Ye, David M. Sabatini, Consuelo Amantini, Julio A. Aguirre-Ghiso, Lawrence H. Boise, Patricia Silvia Romano, Sean T. Sweeney, Takayuki Tsukuba, Reinhard Dechant, Benoit Barbeau, Marta Martinez-Vicente, Kuo How Huang, Edésio José Tenório de Melo, Faustino Mollinedo, José M. Fuentes, Joaquín Jordán, Dong-Hyung Cho, Dexian Zheng, Jeroen J.M. Hoozemans, Zhong Chen, Waleska Kerllen Martins, Abraham Acevedo Arozena, Marcos P. Thomé, Gordon C. Shore, Fabienne C. Fiesel, Teng Jiang, Feng Han, Marc Poirot, Anne Sophie Nicot, Eileen White, Olivier Feron, Arthur I. Cederbaum, Wen Bin Qian, Yingjie Sun, Rejko Krüger, Shingo Kajimura, Jianzhen Xu, Shang Der Chen, Maximiliano G. Gutierrez, Zhengping Yu, Jiaren Sun, Utpal Sen, Giovanna Galliciotti, Hilde Nilsen, Benjamin T. Kopp, Benedikt Westermann, Inmaculada Galindo, Eeva-Liisa Eskelinen, Rubem F. S. Menna-Barreto, Guillermo Mariño, Andrea Ballabio, Izabela Poprawa, Yanjin Zhang, Clay F. Semenkovich, Martin E. Fernandez-Zapico, Helin Vakifahmetoglu-Norberg, Hongchi Jiang, Eugenia Morselli, Angelo A. Manfredi, Marianne Boes, Han-Jung Chae, Covadonga Alonso, Min Chen, Safia Costes, David Kessel, Rakesh Kumar, Yang Zhang, Reinhild Prange, Vassiliki E. Mpakou, Laura Santambrogio, Javier E. Irazoqui, Anna Skwarska, Junichi Sadoshima, Rika Umemiya-Shirafuji, Michael I. Koukourakis, Norma Maugeri, Yuqing Wang, Pedro R. Cutillas, Jiqin Lian, Jiri Stulik, Takashi Ueno, Craig Montell, Rena Balzan, Meiyan Jin, Mara C. Duncan, Cathleen R. Carlin, Yasuo Yanagi, Maite G. Fernandez-Barrena, Yuyan Xiong, Martin Graef, Wei Yuan Yang, Renato V. Iozzo, Mark Screen, Patrick Brest, Haichao Wang, Ming Tan, Werner J. Kovacs, Weili Shen, Alessandro Fraldi, Paul Saftig, Alberto Faggioni, Krisna Prak, Christos E. Zois, Timothy E. Weaver, Marc Lecuit, Yu-Ying He, Michele Caraglia, Walter Balduini, M. Isabel G. Roncero, B. Schneider, Monika Cahova, Mathias Faure, Chihiro Sasakawa, Simon Michaeli, Sandy Giuliano, Dario C. Altieri, Eun-Kyeong Jo, Myung-Shik Lee, Carol Imbriano, John H. Brumell, Gustavo H. Goldman, Yan Wang, Junyan Shi, Quan Chen, Jayanta Debnath, Yonggeun Hong, Mohamed Amessou, Richard W. Wong, Robert E. Burke, Mauro De Santi, Trevor G. Shepherd, Anna Maria Joseph, Wouter G. van Doorn, Erkang Fei, Huey Lan Huang, F. Gisou van der Goot, Xinfeng Liu, Alexandru Almasan, Akiko Maeda, Yu Qiu, Yaohua Wu, Annie Sittler, Wen-Xing Ding, Wenhua Zhu, Hung-Jen Liu, Moisés Martínez-Velázquez, Jeffery S. Cox, Seung Yong Yoon, Concepcio Marin, Wilian A. Silveira, Fulvio Chiacchiera, W. Douglas Fairlie, Jian Xin Gao, Shuilong Leng, Nathan R. Brady, Josef M. Penninger, Puran Singh Sijwali, Florian Gruber, Tibor Vellai, Jiunn-Liang Ko, Laura Korhonen, Slimane Ait-Si-Ali, Hirokazu Arimoto, Alberto M. Martelli, Teresa L. M. Thurston, Chuanshan Xu, Kathrin Pallauf, Eduardo Couve, Shweta Saran, Lionel Blanc, Maylin Almonte-Beceril, Yong-Keun Jung, Lena Lavie, Junsoo Park, Camilla Palumbo, Claire H. Mitchell, Sophie Pattingre, Guillermo Velasco, Steve S.-L. Chen, Xiu-Fen Ming, Xin Qi, Vania Gelmetti, Nicolas Dupont, Soraya S. Smaili, Chinnaswamy Jagannath, Uta Dahmen, Daolin Tang, Rodrigo Franco, John H. Kehrl, Xiaonan Dong, Carsten Sachse, Jeff Kuret, Genzou Takemura, Supawadee Sukseree, Joëlle Botti, W. Haung Yu, Aurelia Lugea, Scott J. Bultman, Divaker Choubey, Frank A. Sinicrope, You-Wen He, Jian Wu, Yoshitaka Isaka, Geert Bultynck, Giuseppe Merla, Luigi Maiuri, Sonia Melino, Hannelore Maes, Daniele Lettieri Barbato, Ian G. Ganley, Zhihong Yang, Daniel Hofius, Kimberly McCall, Peiwen Chen, Istvan Lekli, Alicia Rosello, Eric Ghigo, Atsushi Kuno, Iman Tavassoly, Chris Albanese, Agustín Aranda, Salvatore Pepe, Hong Jiang, Henri Batoko, Giovanna Elvira Granato, Vincent Zecchini, Stephen E. Girardin, Maria T. Diaz-Meco, Philippe Marambaud, G. Amadoro, Sangeeta Khare, Christelle Koechlin-Ramonatxo, Emery H. Bresnick, Christian Behl, Mikio Nishimura, Julien Puyal, Wenjie Guo, Hsinyu Lee, Carolyn M. Sue, Derrick Gibbings, Alina Maloyan, Philippe Pierre, Serge N. Manié, Gerry Melino, Elizabeth A. Woodcock, Roberto Ciarcia, Liwen Jiang, Michael C. Kruer, Vladimir Trajkovic, Yunjiao Zhang, Nina Raben, Beata Pajak, Michael J. Ragusa, Riccardo Autelli, Kelly Jean Thomas, Suzana Gispert, Wei Li Zhao, Cheol Hyeon Kim, Pothana Saikumar, Arsenio Fernández-López, Juliano Machado, Valentina Iovane, Cai Ping Tan, Carmine Settembre, Neelam Azad, Yohta Shimada, Shivendra V. Singh, Hai Rao, Hirosato Mashima, Michael T. Stang, Yasuhito Sakuraba, Gemma Fabriàs, Tuck Wah Soong, Didac Carmona-Gutierrez, Ilse Vanhorebeek, F. Javier Oliver, Mondira Kundu, Alfonso Schiavi, Dan Lindholm, José L. Revuelta, Jason S. King, Susana Castro-Obregón, Paul Digard, Hua Zhu, Komal Raina, Yun Dai, Ruben K. Dagda, Nuria Martinez-Lopez, Andrea A. Gust, Lucia Notterpek, Robert Clarke, Manon E. Wildenberg, Mingzhou Chen, Leticia Reyes, Laura Berliocchi, John J. McMahon, Hongzhuan Chen, E.M. Nolte, Stefan W. Ryter, Fulvio Reggiori, Jiefei Geng, Michael A. Mandell, John H. Fingert, Holger Prokisch, Marina Jendrach, Søren R. Paludan, Elizabeth P. Henske, Ricardo Gargini, Wei-Xing Zong, Susmita Kaushik, Michael Overholtzer, Paul W. Sylvester, Daniel E. Voth, Canhua Huang, Andrea Boman, Gérard Lizard, Rut Valdor, Marc Flajolet, Graham S. Taylor, Nicola Di Daniele, Leonardo H. Travassos, Ying Yang, Anumantha G. Kanthasamy, Hasan Mukhtar, Yuhua Zhu, Noor Gammoh, Ignacio Vega-Naredo, Victoria Ryabovol, Sara W. Bird, Gang Min Hur, Qun-Ying Lei, Fan Yi, Laura Caberlotto, Maria F. Galindo, Bilal Piperdi, Leonidas C. Platanias, P. Hande Özdinler, Régis Delage-Mourroux, Julio Madrigal-Matute, Xu Liu, Nagio Takigawa, Aurora Pujol, Marta Margeta, Hee Jeong Kong, Christian Behrends, Michael Thumm, Shirley Luckhart, Emilio Clementi, John W. Steele, Liliana Schaefer, Philip L. Lorenzi, Chao-Yu Miao, She Min Lu, Jane E. Ishmael, Jin Hyoung Kim, V. Izzo, Yanming Wang, Balindiwe J.N. Sishi, Vincent Galy, Andras Perl, Shouqing Luo, Giovanni Vitale, Yongsheng Che, Rodrigo Troncoso, Liu Yang, Thomas J. Begley, Sebastien G. Bouret, Elizete Rizzo, James M. Piret, Junjun Wang, Herman P. Spaink, Thomas S. Jacques, Robin F. B. Turner, Young H. Lee, Eva Szegezdi, Daphne R. Goring, Manish K. Aghi, Rui Kang, Bart Staels, Midori Umekawa, Delia Goletti, Robert J. Bryson-Richardson, Ubaldo E. Martinez-Outschoorn, Luisa Dalla Valle, Giovanni Luca Gravina, Emad S. Alnemri, Maria Kaparakis-Liaskos, Konstantinos Ritis, Shalmoli Bhattacharyya, Alessandra Bolino, Xiaonan Zhao, Yoshihisa Watanabe, Christian Ungermann, Juan L. Iovanna, Katherine Williams, Ken Shirabe, Teresa S. Hawley, Sara Cherry, Ryuichiro Atarashi, Kozo Hamada, Seamus J. Martin, Shigeru Oshima, Mario Pende, Illana Gozes, Michel A. Duchosal, John J. Shacka, Shunhei Yamashina, Kithiganahalli Narayanaswamy Balaji, Richard L. Proia, Besim Ogretmen, Fang Hua, Koichi Araki, Charles Grose, Jia Luo, Helen K. W. Law, Charles Swanton, Liat Drucker, Guo Zhang, Zhizhuang J. Zhao, Anne K. Kenworthy, Javier A. Menendez, Gary Grant, Stig U. Andersen, Frank Lafont, Aparna Lakkaraju, Taijoon Chung, Leticia A.M. Carneiro, Monique Bernard, Gang Chen, Stephen W.G. Tait, Aimee L. Edinger, Jeffrey P. MacKeigan, Paul A. Ney, Mireia Niso-Santano, Valeria Crippa, Andreas S. Reichert, Isabelle Dugail, Jon D. Lane, Farida V. Minibayeva, Gianluca Tettamanti, Scott Pattison, Péter Lõrincz, Kamal Chowdhury, Ulrich E. Schaible, Maria Agnello, Paolo Pinton, Niels Jessen, Lei Guo, Kwang-Huei Lin, David N. Zacks, Ying Jan Wang, Simone Fulda, John J. Lemasters, Andrea Viale, Anna Maria Marconi, Valerie Askanas, Yoshitaka Nagai, François M. Vallette, Joan K. Heath, Srinivasan Dasarathy, Soo-Youl Kim, Günter U. Höglinger, Tamara Kravic-Stevovic, Iraide Alloza, Tiago F. Outeiro, Ana Serrano-Puebla, Elena A. Minina, Terrence M. Donohue, Ming Guo, Alexandra Giatromanolaki, Abdel Halim Harrath, Ken Sato, Anne Elisabeth Theron, Usha P. Andley, Claudio Cardinali, Maija Pesonen, Penny E. Lovat, Chanhee Kang, Sabah N. A. Hussain, Lisa A. Brennan, Jose A. Tapia, Christoph Becker, Huixin Yu, Pei-Yu Wang, Bertrand Joseph, Zhen Yan, Georgia Minakaki, Ricardo Escalante, Ralph A. Nixon, Katsuhiko Asanuma, M. Helena Vasconcelos, David J. Reiner, Shengkan Jin, David Dávila, Theo Rein, Balakrishna L. Lokeshwar, Antonio Miranda-Vizuete, Carl Ward, Vito Turk, Frederick D. Quinn, Katja Köhler, Masaru Harada, Kathleen Boesze-Battaglia, Fraser P. Coxon, Paulo R. Jannig, Miguel A. Peñalva, Manjula Kalia, Marco Corazzari, Chunjuan Song, Xianghua Yan, Lilach Toker, Benjamin Pineda, Vanessa Ginet, Ye Xu, Chun Jung Chen, Roberto Towns, Amy A. Kiger, Rajagopal Ramesh, Maria Rita Rippo, Joseph A. Hill, Boris Zhivotovsky, Peter Speck, Ya Hua, Peter J. Roach, Fabio Penna, Kasper M.A. Rouschop, Jeng-Jer Shieh, Maria Angeles Mena, Mei Zhao, Sonia Rocha, Xin Wen, Sylvain Lefort, Michael Scharl, Ramnik J. Xavier, Alan Cheng, Marion Bouchecareilh, Stella Y. Lee, Maria Xilouri, Qi Chen, Claudia Spies, Pengfei Ge, Natascia Ventura, Luca Galluzzi, Yau Hung Chen, Jing Pu Zhang, Diego Albani, Dingzhong Tang, Nikolai Engedal, Stefania Meschini, Maria Lyngaas Torgersen, Shibu M. Poulose, Jean-Paul Decuypere, Ziheng Xu, Jocelyn Laporte, Thierry Arnould, Albert Haas, Ida J. van der Klei, Agustín Hernández, Dong Wook Shin, Per E. Stromhaug, Valentín Ceña, Ugo Pagnini, Karolina Pakos-Zebrucka, Blagovesta Popova, Lisa M Lindqvist, Sangita C. Sinha, Yuguang Shi, Zvonimir Marelja, Robin Candau, Xin Wang, Evelina Gatti, Olatz Pampliega, Michael P. Lisanti, Elena Tamagno, Mei Lan Tan, Gary Warnes, Zdena Palková, Shigeomi Shimizu, Ingo Schmitz, Tino Kurz, Soledad Matus, Gopal Chakrabarti, Joseph J.Y. Sung, Beáta G. Vértessy, Giuliana Cassinelli, Giovanni Benard, Yin Chen, Emma Colucci-Guyon, Craig Blackstone, Lizhi Cao, Sebastian Schuck, Qingqiu Gong, Theocharis Panaretakis, Jayoung Choi, Sven R. Carlsson, Libuše Váchová, Raymond Chuen-Chung Chang, Yang Liu, Zheng Dong, Qinghua Shi, Hélène Duez, Tiziana Bachetti, Axel H. Schönthal, Sumit Sahni, Bo Wang, Naomichi Matsumoto, Markus Rehm, Liliana Torosantucci, Toren Finkel, Yi Hsin Tseng, Hsiang Cheng Chi, Fang Lin, Tony George Jacob, Ju-Xian Song, Alessandro Fanzani, Marc Tatar, Paola Costelli, Rubén Gómez-Sánchez, Yunfei Wen, Juha J. Hulmi, Francesca V. Mariani, Min Zeng, Chiung Chyi Shen, Carine Michiels, Yan Burelle, Andreas L. Serra, Goran Petrovski, Kwang Woon Kim, Paula Ludovico, Darius Ebrahimi-Fakhari, Yee Joo Tan, Luisa De Martino, Alvaro Glavic, Pierre Lapaquette, Edmund B. Rucker, Andreas Mayer, Shigeko Yamashiro, Scott K. Powers, Robert M. Gogal, Ebru Goncu, Yuichiro J. Suzuki, Anna Maria Giammarioli, Claudio Hetz, Eric H. Baehrecke, Cheryl L. Walker, Cinzia Lanzi, Deepti S. Wilkinson, Ralph Feuer, Long Yi, Virawudh Soontornniyomkij, Nektarios Tavernarakis, Nobuyuki Nukina, Elisabetta Ferraro, Thomas Wollert, Vassiliki Karantza, Simon Wilkinson, Yong Tae Kwon, Panagiotis D. Velentzas, Jong-In Park, Huu Phuc Nguyen, Miriam J. Schönenberger, Marcello Chieppa, Thomas A. Ferguson, Behzad Yeganeh, Saurabh Chatterjee, Anika Nagelkerke, Ju Hong Jeon, David W. Russ, Jeff W. Chen, Verónica I. Dumit, Chuangui Wang, Stephen C. Pak, Georgios Chamilos, Vijittra Leardkamolkarn, L. Ashley Cowart, Miguel A. Martín-Acebes, Andrea Cossarizza, László Orosz, X. Charlie Dong, Kei Watase, Yasuko Rikihisa, Santiago Rodríguez de Córdoba, Yu Jen Chen, Andrew P. Lieberman, Peter G.H. Clarke, Guylène Page, Babak Razani, Franziska Wild, Guang Zhou Zhou, Tsui-Fen Chou, Gen Sheng Wu, Daniel Johnson, Jiwu Wei, Rani Ojha, Marco Molinari, Manolis Fanto, Yongjun Jiang, Nadine Camougrand, Rong-Rong He, Ivan Dikic, Candece L. Gladson, Naoki Suzuki, Shiming Liu, Felipe X. Pimentel-Muiños, Alicia Meléndez, José Antonio Sánchez-Alcázar, Maho Hamasaki, Carmen Ruiz-Roldán, Hana Schmeisser, Margarita Villar, Vinod Sundaramoorthy, Maria Beatrice Morelli, Naweed I. Naqvi, Jochen Klucken, Nirmala Parajuli, Rodney J. Devenish, Mari L. Shinohara, J. Lindsay Whitton, Marie-Josée Boucher, Jeroen Roelofs, Xiao Hong Liu, Saverio Minucci, Germán Bou, Katie R. Martin, Hermann M. Schätzl, Suresh C. Tyagi, Shengzhou Wu, Michael T. Lotze, Albert R. La Spada, Channing J. Der, Gabriela Roca, Lucile Espert, Elisabeth Corcelle-Termeau, Zhenyu Yue, Sabine Hilfiker, Evripidis Gavathiotis, Truong Lam, Tobias M. Rasse, Kumaravel Somasundaram, Chih-Wen Shu, Tamotsu Yoshimori, Daniel T. Starczynowski, Oliver Florey, Vladimir Kirkin, Dan T. Vogl, Peter Vandenabeele, Allan Tsung, Renwick C. J. Dobson, Serge Mostowy, Nelly Godefroy, Maria Teresa Viscomi, Young Ho Koh, Caroline Mauvezin, Keiji Tanaka, Juan Fueyo, Lih-Shen Chin, Jingjing Cai, Laura D. Osellame, Maurizio Battino, Małgorzata Gajewska, Maria I. Vaccaro, Darius J.R. Lane, Yuji Ogura, Ian G. Mills, Gil Leibowitz, Joan Villarroya, Yu-Chen Hu, Maria Teresa Batista, Vojo Deretic, Manoj B. Menon, Zhenyi Ma, Dawit A. P. Gonçalves, Iban Seiliez, Enzo Emanuele, Ho Shin Gwak, Arnim Pause, Francesca Palladino, Cristiano Simone, Angelica M. Merlot, Peng Wang, Liang Ge, Kenneth Maiese, Ken Cadwell, Sally S. Atherton, Deepak Shukla, Thomas Neill, Jean-François Beaulieu, Barry Jutten, Cristina P.R. Xavier, James Murray, Tatsuya Saitoh, Roberto Chiarelli, Benedetto Grimaldi, Antonio Giordano, Yanjun Kou, Cathy Tournier, Romana T. Netea-Maier, Rui Li, Jason L. Eriksen, Colin D. Weekes, Esther Barreiro, Denis Mottet, Derek P. Narendra, Karl Swärd, Stephanie E. Wohlgemuth, Gary A. Silverman, Yukitoshi Nagahara, Mark J. Walker, Roland Malli, Diane M. Ward, Ling Hua Meng, John D. MacMicking, Cinzia Fabrizi, Marco Tucci, Tomasz M. Stepkowski, Wannian Yang, Yi Zhen Deng, Daret K. St. Clair, Darren J. Moore, Michael Lee, Katia Aquilano, Norbert Frey, Tibor Kovács, Ru Jeng Teng, Federico Pietrocola, Alfredo Criollo, Nadia Jaber, Walter T. Klimecki, Xiaohong Zhuang, Beata Sikorska, Inmaculada Tasset-Cuevas, Iwona A. Ciechomska, Robert C. Dickson, Haruo Kanno, Hua She, Xiaolei Xu, Maria Laura Avantaggiati, Isei Tanida, Jun Li, Diego Pérez-Rodríguez, Agnieszka Bagniewska-Zadworna, Viktor I. Korolchuk, Thirumala-Devi Kanneganti, Simone Nardin Weis, Thorsten Nürnberger, Guanghui Wang, Luigi Puglielli, Valina L. Dawson, Santosh Chauhan, Carole Kretz-Remy, Po-Yuan Ke, Haijun Bao, Patrícia Sampaio Tavares Veras, Sharad Kumar, Guo-Qiang Chen, Congfeng Xu, Annie M. Joubert, Diego L. Medina, Andrea Hamann, Christian Münz, Hongchuan Jin, Zhen Chen, Cristina López-Vicario, Seung Il Choi, Ivanka Markovic, Ronit Pinkas-Kramarski, Lei Jin, Yonghyun Kim, Michael J. Clague, James D. Johnson, Areti Pantazopoulou, Mohamed Al-Rubeai, Si Chen, Anne Spang, Matteo Bordi, Xiaowei Wang, Stefanie Pöggeler, Terrence M. Donohue-Jr, Aldrin V. Gomes, Jawahar L. Mehta, Yuuki Fujiwara, Mihai G. Netea, Ezra E.W. Cohen, Yunfei Huang, Do Hyung Kim, Guido Lenz, Qian Cai, Chenran Wang, Anna Katharina Simon, Barbara Del Bello, Robert Layfield, Taehoon Chun, Margit Burmeister, Wei Liu, Peter D. Adams, C. K.James Shen, Iva Slaninová, Kathleen W. Scotto, Erinna F. Lee, Mireille Verdier, Fernando J. Peña, Nicola Brunetti-Pierri, Eun-Kyoung Choi, Aleksandra Isakovic, Ju-Hyun Lee, Swapan K. Ray, Ming Chang Hu, Stephen Baghdiguian, Davide Cervia, Brent R. Stockwell, Maurizio Sorice, Andreas Till, Victor M. Darley-Usmar, Horng-Dar Wang, Ken H. Young, Yibin Feng, Néstor L. Uzcátegui, Andreja Erman, Manuela Antonioli, Alicia Torriglia, Michael D. Kim, Kazuyuki Kuchitsu, Fabio Di Domenico, Claudia Giampietri, Fuyong Song, Kevin E. Behrns, Craig Stevens, A. Sue Menko, Joana Liberal, Antonio Di Pietro, Xuejun Jiang, Joseph D. Mancias, Maria Tiziana Corasaniti, Frédéric Gros, Fuxin Wang, Jeremy Thorner, Areechun Sotthibundhu, Gijs R. van den Brink, Andrei S. Chagin, Rossella Menghini, Francesca Bernassola, Chi Li, Sung Gil Chi, Enrico Milan, Jean M. Mulcahy Levy, A. Murat Kaynar, Maria João Sousa, Olga Corti, Simone Cenci, Ting-Fang Wang, Carlos Hernández, Sucheta Telang, Zun-Ji Ke, Atsuo Amano, Lihuan Du, Meera Nanjundan, Lin Zhang, Matthias Gaestel, Bertrand Kaeffer, Andrey S. Tsvetkov, Silvia Carloni, Kazuhisa Hasui, Rosa Puertollano, Vladimir Bumbasirevic, Yongchao Zhao, Carolyn B. Coyne, Allan Caplan, Per Ottar Seglen, Kotb Abdelmohsen, Andreas Buch Møller, Jenny P.-Y. Ting, Raquel Muñoz-Moreno, Markus A. Rüegg, Monica Hagedorn, Hao Zhang, Tomotake Kanki, Edoardo M. Airoldi, Melanie Schwarten, Alfred J. Meijer, Anne Bertolotti, Matteo Bergami, Joëlle Wiels, Claudia Cerella, Eric Asselin, Z. H. An, Spencer B. Gibson, Chunlai Wu, Kai Kaarniranta, Paloma B. Liton, Feng Jun Li, Roberta Nardacci, Ernst J. Wolvetang, Robert C. Bast, Mark S. Cragg, Quentin Liu, Massimo Federici, Hyun Kyu Song, Hua Bai, Xiaotao Li, Nils J. Færgeman, Jason Chesney, Shrawan Kumar Singh, Marcello D'Amelio, Mark Prescott, Georg Auburger, Shazib Pervaiz, Allen Taylor, Diane C. Bassham, Lei Wan, Michinaga Ogawa, Emilia Maellaro, Cynthia Y. He, Chris Jones, Paolo Grumati, Jun-Lin Guan, Hiroyasu Nakano, Eric A. Schon, Roswitha Krick, Yoshihiro Shidoji, Jaime L. Schneider, Dusica Maysinger, Thomas Thum, Paul G. Thomes, Edo Vellenga, Liang Liu, Giuseppe Filomeni, Niramol Savaraj, Rudolf A. Kley, Wei Jung Chen, Bradley L. Baumgarner, Victor H. Villar, Steven Finkbeiner, Kapil Sirohi, Francesco Cecconi, Steven S. Witkin, Steve Jean, André du Toit, Rossella Russo, Irina Petrache, Randy Schekman, Keisuke Hino, Wei Chen, Basil J. Petrof, Daniel E. Frigo, Gyun Min Lee, Paul N. Span, Megumi Inomata, Ivica Arsov, Zhi-Xiang Xu, Saeid Ghavami, Tania C. Felizardo, Konstanze F. Winklhofer, Weidong Han, Jianhua Zhang, Eva Maria Mandelkow, Lydia Alvarez-Erviti, Wanderley de Souza, Pawel P. Liberski, Yang Sun, Cornelia M. Weyand, William D. Hill, Eric J. Brown, Christopher M. Adams, Felix Randow, Jose Luis Rosa, Ivan R. Nabi, Patricia V. Aguilar, Laure Aurelian, Jae-sung Bae, Gábor Juhász, Hing Y. Leung, Karla Kirkegaard, Peter J. O'Dwyer, Daniele Bergamaschi, Thomas Farkas, Tsunenori Saito, Laura Knuppertz, Leyuan Liu, Dongxu Fu, Liesu Meng, Alon Kahana, Viktor Billes, Shohreh Issazadeh-Navikas, Ljubica Harhaji-Trajkovic, Xiangguo Liu, Takahiro Yamada, Ciro Isidoro, Huiping Zhou, William A. Dunn, Takeshi Into, Giampietro Viola, Eumorphia G. Konstantakou, G. William Wong, Peter W. Szlosarek, Jeffrey S. Isenberg, Mikkel H. Vendelbo, Zuzana Papackova, Carlos B. Gonzalez, Hong Zhang, Alkesh Jani, Heidi Kiil Blomhoff, Wen-Li Chen, Simon Sedej, François Bertrand Favier, Marina K. Holz, Mitsunori Fukuda, Gudmundur Vignir Helgason, Fu-Cheng Lin, Inés Díaz-Laviada, Stefaan J. Soenen, Chao Yung Wang, Chee Yin Chai, Pierre-André Bédard, Xiaoxiang Zheng, Peter V. Bozhkov, Han-Ming Shen, Hazel M. Davey, Pedro A. Lazo, Haoxing Xu, Fengtian He, Jean Max Pasquet, Benoit Pasquier, William T. Jackson, Stéphane Duvezin-Caubet, Bertrand Mollereau, Tomohiro Kabuta, Maria Rosa Ciriolo, Peter Hasselblatt, Nihar Ranjan Jana, Jane L. Armstrong, Elisa Giovannetti, Fang Lin Sun, Zhenyu Yao, Shuji Kishi, Pei-Hui Lin, Yingmei Zhang, Limor Avrahami, Kenichi Shibuya, Guillaume Dalmasso, Radovan Vasko, Sharon Prince, Valerie B. O'Donnell, Gordon B. Mills, Hiroshi Aoki, Maryam Mehrpour, Muniswamy Madesh, Guillermo Díaz-Araya, Susan L. Cotman, Marius K. Lemberg, Tilman Grune, Jing Lan Liu, Richard C. Wang, Sandro Goruppi, Hongmin Wang, Robert A. Heinzen, Xiangmei Chen, Nihal Altan-Bonnet, Sung Sik Lee, Hai Jie Wang, Catherine Dargemont, Jie Du, Sofie Claerhout, Edmond Chan, Yi Sun, Xiangbo Wan, Paul Lingor, Shilpa Buch, Gerald M. McInerney, Zhenlong Wu, Guo Chang Zhang, Iain A. McNeish, Suresh Awale, Mark P. Mattson, Srinivasa Subramaniam, Wuhan Xiao, Katsuhiko Mikoshiba, Giancarlo Parenti, Bruno Miguel Neves, Benjamin Dehay, Fatima Teixeira-Clerc, Patricia Huebbe, Calvin K. Yip, Ryan J. Schulze, Pallabi Sarkar, Vladimir I. Titorenko, Johanna Laukkarinen, Martin E. Gleave, Veronika Stoka, Pascal Genschik, Karen Brown, Zhaoliang Su, Walter Malorni, Arlette Darfeuille-Michaud, Vincent C. O. Njar, Jeffrey E. Pessin, Thomas Wileman, Alexander J. Whitworth, Stefano Santaguida, Gustavo A. Nader, Gláucia Maria Machado-Santelli, Marie-Josée Hébert, Skye C. McIver, Scott A. Soleimanpour, Jia-Hong Lu, Fei Liu, Yu Wang, Elisa Motori, Chad A. Dickey, Andrej Udelnow, Ahmed Hamaï, Junying Yuan, Jan Paul Medema, Michelangelo Campanella, Abhishek D. Garg, Pallavi Chandra, Marco Mongillo, Bonnie Bartel, Thomas Weide, Yong Joon Chwae, Nancy Y. Ip, Yoshiaki Kamada, Hikmet Budak, Jian Xiao, Mario D. Cordero, Wei Li, Muzamil Majid Khan, He Jin Lee, Meng-Chao Yao, Zu-Hang Sheng, Perrine Castets, Dongsheng Cai, Morten Petersen, Javier Díaz-Nido, Yong Lin, Kaio Kitazato, Yotaro Izumi, Beatrice Y.J.T. Yue, Des R. Richardson, Chunsun Dai, Michael Hensel, Ronit Sagi-Eisenberg, Chan Ding, Christian Sell, Idil Orhon, Wilhelm Krek, Qutayba Hamid, Salem Chouaib, Rajkumar Banerjee, Hsing Yu Tuan, Eyleen J. O’Rourke, Fathia Mami-Chouaib, Ryo Ushioda, Hidekazu Suzuki, Jie Fan, Anders H. Lund, Urban Emmenegger, Brigit E. Riley, Andrew Thorburn, Kailash Gulshan, Karol Dokladny, José M. Cuezva, Daniel T. Ruan, Salik Hussain, Mohamed Rahmani, Maria Teresa Bassi, Miquel Vila, Pavel Strnad, Terry H. Landowski, Christiaan Leeuwenburgh, Hagit Eldar-Finkelman, Francesco Fornai, Vincent Kam Wai Wong, Hengyi Xiao, Massimo Nabissi, Luciano Merlini, Chris Williams, Jatin M. Vyas, Motoko Sasaki, Chwen Ming Shih, Saveria Aquila, Marina Garcia-Macía, Po Wu Gean, Yasuo Kitajima, Gian Luigi Russo, Tania Zaglia, Arnaud Moris, Alessandra Stacchiotti, Elaine Gutierrez, Iain D. C. Fraser, Paolo Salomoni, Ramón Corbalán, Dave Bridges, Juan P. Liuzzi, Rosanna Parlato, Sandrine Silvente-Poirot, Carl G. Maki, Patty J. Lee, Paulo Pereira, Vitaliy O. Kaminskyy, Rajaraman Eri, Bertha Brodin, Tobias Eisenberg, Rong Yu Liu, Yide Mei, Pearl P.Y. Lie, Bradford G. Hill, Yoshio Fujitani, Angelika A. Noegel, Nadarajah Vigneswaran, Muriel Mari, Steven Grant, Davide Romanelli, Lee Ann MacMillan-Crow, Anna-Lena Ström, David Sulzer, Aditya Murthy, Lisa B. Frankel, Yong Ma, Ok-Nam Bae, Pablo Wappner, Chun Hei Antonio Cheung, Young Hyun Yoo, Andreas Linkermann, Kirill V. Rosen, Orsolya Kapuy, Simone Di Paola, Thomas J. Evans, Rosa A. González-Polo, Jin H. Son, Kinya Otsu, Tracey R. O’Donovan, Nicolas Pallet, Stefano Toldo, Wafik S. El-Deiry, Allen Kaasik, Jin Tai Yu, Susu M. Zughaier, Gordon W. Laurie, Barbara Guerra, Taeg Kyu Kwon, Priyamvada Dua, Stephen A. Spector, Yingyu Chen, Ayesha N. Shajahan-Haq, Wei Pan, Matthew Campbell, Leo A. B. Joosten, J. Paul Taylor, Julian J. Lum, Matthew J. Justice, Clarissa von Haefen, William K.K. Wu, Gerald Rimbach, Peter Polčic, Jens Schmidt, Saverio Bettuzzi, Xian De Liu, Satoru Kobayashi, Yan Zhang, Ling Tian, Péter Nagy, Mercedes Pozuelo-Rubio, Cheng Jin, Marek Los, Hiroyuki Ishida, Yuji Moriyasu, Maria Teresa Cruz, Jingjing Liu, Anil K. Sood, Roberto Mateo, Antonio Facchiano, J. Mark Cooper, Xiaofeng Yao, Pei Ming Yang, Eli Arama, Marc Diederich, Luc J. W. van der Laan, Robin Ketteler, James Harris, Eui Ju Choi, Grant R. Campbell, Julie D. Atkin, Janos Kriston-Vizi, Sharon L. McKenna, Mila Ljujic, Hirotaka Watada, Harry Ischiropoulos, Shile Huang, Udo Hasler, Ke Li, Josefina Casas, Ken-ichi Isobe, Min Li, Muriel Priault, Vincenzo De Tata, Monique Gannagé, Sakineh Kazemi Noureini, Isao Ishii, Sasanka Ramanadham, Valérie Pierrefite-Carle, Chengyu Liang, Louise Deldicque, Gabriella Cavallini, Afshin Samali, Angelika Amon, Kah-Leong Lim, Lavinia Cantoni, Demetrios G. Vavvas, James E. Haber, Alireza R. Rezaie, Regina Celia Bressan Queiroz de Figueiredo, Cynthia D. Cooper, Masaaki Komatsu, Silvia Alvarez, Gemma Triola, Dong-Yun Ouyang, Razaul Karim, Kostyantyn V. Dmytruk, Bassam Janji, Peter Bütikofer, Indira U. Mysorekar, Hana Popelka, E. Marion Schneider, Carlos Guillén, Gaël Roué, Seung-Hoon Baek, Patrick Auberger, Jun Araya, Sandra M. Cardoso, Gu He, Eduardo C. Filippi-Chiela, Patrick A. Lewis, Wei-Pang Huang, Eric Reits, Cécile Vindis, Trond Lamark, Mehrdad Alirezaei, Takao Setoguchi, Alberto Bartolomé, Chih Peng Chang, Andriy A. Sibirny, Mauro Piacentini, Jing Wang, Kuninori Suzuki, Ludo Van Den Bosch, Kevin N. Dalby, Keiran S.M. Smalley, David K. Ann, Luis F. Moita, Anthony Sanchez, Chin Hsu, Guillermo M. Albaiceta, Vassilis Stratoulias, Attila L. Kovács, Charleen T. Chu, Tewin Tencomnao, Audrey H. Poon, Steve Lancel, José C. Fernández-Checa, Hannah Rabinowich, Heinz D. Osiewacz, Sami Dridi, Kate E. Keller, Thorsten Hoppe, Crispin R. Dass, Jekaterina Erenpreisa, Akira Matsuura, Donna D. Zhang, Ying Zhao, Luisa Coletto, Roy Parker, Georg M. N. Behrens, Alessia Di Nardo, Mian Wu, Alberto Jiménez, Magdalena Rost-Roszkowska, Christopher J. H. Elliott, Pamela J. Yao, Damián Gatica, Rafael Linden, Helena L. A. Vieira, Anand K. Ganesan, Wim Martinet, Frank Madeo, Juliann G. Kiang, Helmut Kramer, Lorrie A. Kirshenbaum, Salvador Ventura, Clemens Steegborn, Zahra Zakeri, Marco Antonio Meraz-Ríos, Masaki Ohmuraya, Michael A. Riehle, Congcong He, Federica Sotgia, Shi-Mei Zhuang, Paul Dent, Jürgen Bosch, Xuejun Wang, Kuan-Chih Chow, Carlos Gorbea, Lisa Gerner, Yuzuru Imai, Jan Gunst, Duncan R. Smith, María Esther Pérez-Pérez, N. Tony Eissa, Michel Roberge, Carmen García-Ruiz, Irfan J. Lodhi, Hongjiao Ouyang, Mustapha Kandouz, Alessio Papini, Jun Sun, Takanobu Otomo, David H. Perlmutter, Jae-Sung Kim, Feng Gao, Åsa B. Gustafsson, Paul M. Salvaterra, Michael Klinkenberg, Or Kakhlon, Abhinav Diwan, Takahiro Shintani, Paola Matarrese, Marc D. Meneghini, Jinsheng Zeng, Xu-jie Zhou, Linda S. Yasui, Rui Sheng, Shiqian Huang, Elizabeth Delorme-Axford, Amélie Bernard, Kevin M. Ryan, Cecília M. P. Rodrigues, Jonathan M. Backer, Harald Stenmark, Hiroaki Adachi, Koichi Sakakura, Fatima Mechta-Grigoriou, Zhi Nong Wang, Ramesh Natarajan, Tian Xia, Marco Folini, Robert A. Screaton, Jane J. Yu, Xian Wang, Gerhard H. Braus, Min Wu, John A. Hanover, Anuj Kumar, Charbel Moussa, Shailendra Anoopkumar-Dukie, Edward A. Fon, Ted Powers, Thomas H. Kawula, Zhe Liu, Jennifer Martinez, Orian S. Shirihai, Mara Cirone, Fen Wang, Machiko Sakoh-Nakatogawa, Yong Xia, Durga Nand Tripathi, James T. Handa, Nadia Zaffaroni, Esther Wong, Carlos López-Otín, Michael E. Cheetham, Harm H. Kampinga, Leopold Eckhart, Paul de Figueiredo, Xueqin Liu, Michael S. Goligorsky, Valentina Sica, Marco Sandri, Wen Qiang Chen, Szabolcs Takáts, Lilach O. Lerman, Akio Kihara, Constantinos Koumenis, Sergio Comincini, Antoinette Lemoine, Marc Bitoun, Zhuo-Wei Hu, Yu Xiong Su, Jeremy C. Mottram, Miguel A. Sanjuan, Richard D. Vierstra, Angelo De Milito, Marjolein van Egmond, Xi-Long Zheng, Kun-Liang Guan, Katrin Juenemann, Ohkmae K. Park, Eisuke Itakura, Bo Yan, Tim Lahm, Yongshun Chen, Kenneth L. van Golen, Federica Rizzi, Guochang Hu, Volker Doetsch, Chengtao Her, Conrad C. Weihl, Jing Hsiung James Ou, Chiou Feng Lin, Dun-Sheng Yang, Bozena Gabryel, Xiao Feng Zhu, Jackie de Belleroche, Charles L. Edelstein, Julie Gavard, Miklós Sass, Maria Chiara Maiuri, Zhendong Zhao, Pu Duann, Julián Pardo, Atsuhiro Ichihara, Lester M. Davids, Swamynathan Ganesan, Shengyun Fang, Hernando Gomez, Yun Chau Long, Mark J. Czaja, Arnaud Echard, Pilar Gonzalez-Cabo, Chuanyong Guo, Katherine L. Cook, Isabel Varela-Nieto, Li Yu, Yi Ran Huang, Binfeng Lu, Athanassios D. Velentzas, Koji Yamanaka, Giuseppe Russo, Ester M. Hammond, Kelsey B. Law, Sheng Li, Samisubbu R. Naidu, Michael E. Boulton, Anna-Mart Engelbrecht, Ba-Bie Teng, Zixu Mao, Vania M.M. Braga, Núria S. Coll, Eliana M. Coccia, Akihisa Abe, V. Ashutosh Rao, Nava Segev, Regina Menezes, Zufeng Ding, Hyman M. Schipper, Álvaro F. Fernández, Peter K. Kim, Lucia Micale, Biplab Dasgupta, Nazzy Pakpour, Janna L. Morrison, Yue Qin Chen, Rolf J. Craven, Zvulun Elazar, Anders Aune Tveita, Lian Li, Hsueh Fen Juan, Ulrich Koenig, Qiang Shi, Harald W. Platta, Michele S. Swanson, Olga V. Voitsekhovskaja, Bruce H. Reed, Malene Hansen, Paola Lenzi, Sandra Cottet, Yacine Graba, Christian Frezza, Bernd Schröder, Helene Knævelsrud, Li Chung Hsu, Hyunjung Jade Lim, Michael T. Greenwood, Parco M. Siu, Kyu Lim, Dolores Pérez-Sala, Patrice Codogno, Yi Yang, Frank Lezoualc'h, Ida Perrotta, Elaine A. Dunlop, Jörg H W Distler, Ken Ichi Yoshida, Dominic P. Del Re, Luigina Romani, Hye Young Kim, Eric Jonasch, Rajesh Agarwal, Wei Song, Ai Yamamoto, Zully Pedrozo, Steffan T. Nawrocki, María Salazar-Roa, Jorrit M. Enserink, Dong Wang, Flaviano Giorgini, Takayuki Ohshima, Boris Turk, Anastasia S. Mihailidou, Rosa Salvioli, Anne Simonsen, Caroline Biagosch, Glauber Costa Brito, Junko Oshima, Gail V.W. Johnson, Emmanuel Taillebourg, Sovan Sarkar, Shane Deegan, Eldad Zacksenhaus, Laura Avagliano, Byung-Hoon Lee, Weiliang Xia, Paolo Paganetti, Timothy J. Lyons, Christine M. Stellrecht, Jane E.B. Reusch, Raquel T. Lima, Feng Xu, James M. Phang, Hongwei Xu, Claudio Luparello, Mohammad Ishaq, Maureen E. Murphy, Isabelle Coppens, Luc Dupuis, Elio Ziparo, Patrick J. Bednarski, Svetlana Saveljeva, Ashok Kumar, Hongxin Zhu, Tobias B. Huber, Günther Weindl, Claudine Kraft, Dhiraj Kumar, Sara Marinelli, Karin von Schwarzenberg, Lijun Jia, Tiziana Crepaldi, Ke Liu, Eleonora García Véscovi, Qing Lu, Cláudia N. Santos, Bertrand H. Rihn, Jun Yu, Fen-Biao Gao, Flavio Flamigni, Jason E. Gestwicki, Dong-Hun Bae, Gustavo C. MacIntosh, David A. Leib, Giorgio Santoni, Chin Yuan Hsu, Abdelhaq Rami, Joseph Satriano, Matthew J. LaVoie, Paloma Martín-Sanz, Daniela De Zio, Sharon M. Gorski, Yu Tian Wang, Shuyan Lu, Clara L. Oeste, Andrew R. Tee, Koji Itahana, Xuesong Yang, Shuiping Tu, Malathi Krishnamurthy, Anne M. Strohecker, Gui Xian Xia, Helena Orozco, Sujit K. Bhutia, Hongbo Hu, Rupert Beale, Ying-Ray Lee, Kai Mao, Pierre-Emmanuel Rautou, Jean Francois Groulx, James A. Mastrianni, Victoria El-Khoury, Koji Okamoto, Mark J. Taylor, Arianna L. Kim, José M. Izquierdo, Dalibor Mijaljica, Björn Stork, Thomas Schwarz, Savita Bhalla, Menno van Lookeren Campagne, Long Zhang, Elizabeth S. Yeh, Li Zhang, Tae Cheon Kang, Frederic Luciano, Shusaku Shibutani, Luciana Dini, Valentina Cianfanelli, Sara Calatayud, Yong-Sun Kim, Maurizio Molinari, Graham H. Coombs, Takeshi Noda, Angelo Poletti, Silvia Palumbo, Dhan V. Kalvakolanu, Valérie Vouret-Craviari, Volodymyr Y. Nazarko, Salvatore Florio, Noboru Mizushima, Arthur Kaser, Shigeki Miyamoto, Patric J. Jansson, Thomas I-Sheng Hwang, Daniel J. Jackson, Adrian L. Harris, Srikanta Dash, Yeong Min Yoo, David Colecchia, Ute C. Meier, Yi Ma, Tadashi Suzuki, Anand Krishnan V. Iyer, Flavia Radogna, Paul S. Brookes, Deepak Kumar, Gabriella D'Orazi, Barry Yedvobnick, David R. Soto-Pantoja, Christian Waeber, Craig McCormick, Dong Hu, Sarron Randall-Demllo, Gustavo J.S. Pereira, Emil Rudolf, Scott L. Friedman, Paolo Bonaldo, Oliana Carnevali, Guido R.Y. 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Tooze, Antonio Zorzano, Jin Cheon Kim, Jian Xu, Andreas Meryk, Kristina Vuori, Jongdae Lee, Patrizia Agostinis, Diego Ruano, Wim Vandenberghe, Julia I-Ju Leu, Céline Gongora, Bernadette Carroll, Vinoth Kumar Megraj Khandelwal, Bo Lu, Marja Jäättelä, Lorenzo Galluzzi, Ioannis P. Trougakos, Tatsuya Maeda, Marie-Agnès Bringer, Mario Chiong, Hans-Uwe Simon, Lance A. Liotta, Ruth S. Slack, Ina Oehme, Umamaheswar Duvvuri, Shaun Martin, Augustine M.K. Choi, Michel Vidal, Ying Wang, Isis do Carmo Kettelhut, Mojgan Djavaheri-Mergny, Jörn Coers, Massimo Donadelli, Jesus Aldudo, Miyuki Sato, Jianxun Liu, Jörg Höhfeld, Luc Van Kaer, Andrei I. Ivanov, Dohun Pyeon, José M. Bravo-San-Pedro, Jianxin Peng, Xiaoyan Jiang, Dimitri Krainc, Yangqing Xu, Arnaud François, P. Robin Hiesinger, Sagar Lonial, William C. Cho, Caty Casas, Betty Yuen Kwan Law, Hongbing Zhang, Tor Erik Rusten, Erwin Knecht, Honglin Luo, Shi Xiao, Hiromi Sesaki, Enza Maria Valente, Verónica Pérez de la Cruz, Marta M. Lipinski, David A. Hood, Shi-Yong Sun, Luiz Carlos Carvalho Navegantes, Joynal Abedin, Shino Goto-Yamada, Gustavo Maegawa, Takehiko Matsushita, Vitor A. Lira, Clara I. Rodríguez, Ekihiro Seki, Qiang Li, Karin Öllinger, Ted M. Dawson, Ssang-Goo Cho, Wan-Wan Lin, Pramod Kumar Garg, Jeffrey Robbins, Peter R. Williamson, Michael Sacher, Carlo Follo, Bulent Ozpolat, Xiao Jia Wang, Na Man, Hua Cheng, Bing Yan, Tsung-Hsien Chuang, Paul B. Fisher, Rajat Singh, Edward A. Ratovitski, Katsuhiko Kitamoto, Jung Jin Hwang, Shinji Hadano, Che Hsin Lee, Shuo Wang, Einar M. Sigurdsson, Camille Martinand-Mari, Agnieszka Sirko, Katherine R. Parzych, Etienne Morel, Yasushi Kitaoka, Hassan Chaachouay, Patricia Chakur Brum, Dexin Kong, Jerome Tamburini, Kuppan Gokulan, Stefan Olsson, Bilon Khambu, Lea M.D. Delbridge, Daniel P. Orban, David A. Gewirtz, Zhonglin Xie, Joe Quadrilatero, Kunikazu Tanji, Simin Mohseni, Gábor Bánhegyi, Jin Ming Yang, Jinxian Xu, Carmen Veríssima Ferreira-Halder, Addanki P. Kumar, Deok Ryong Kim, Jianjie Ma, Sang Won Suh, Guido Kroemer, Klára Megyeri, Michael N. Sack, Heinrich Taegtmeyer, Gilles Pagès, Gabriella Marfe, Gregg L. Semenza, Karine G. Le Roch, Marisa Brini, Marina Bouché, Oliver Kepp, Vinay V. Eapen, J. David Beckham, Stephan T. Stern, Xudong Zhang, Marcello Pinti, Xiangnan Zhang, Jae Keun Lee, Ana Coto-Montes, Assaf Rudich, Laura D. Attardi, Debabrata Ghosh, Philip Rosenstiel, Sébastien Besteiro, Maria Rosa Sarrias, R. Andres Floto, Xiao Ming Yin, Nicholas W. Lukacs, Hermann Pavenstädt, Matias Simons, Hitoshi Nakatogawa, Sandro Alves, Krisztina Takács-Vellai, Masato Koike, Debasish Sinha, Shoji Notomi, Faraj Terro, Maria Carmela Roccheri, Santiago Ambrosio, K. Ulrich Bayer, Yumin Li, Terje Johansen, Christian Kuhn, Yee Shin Lin, David C. Rubinsztein, Ziwei Qu, Ronit Shiri-Sverdlov, Emmanuel T. Akporiaye, Galila Agam, Hui Ling Chiang, Seung-Jae Lee, Yu Xue, Francesca Giampieri, Markus Damme, Tassula Proikas-Cezanne, Tianwei Lin, Marc Kantorow, Guang-Chao Chen, Qiangrong Liang, Claudia Manzoni, Joan S. Steffan, Emilio Boada-Romero, Damien Freyssenet, Sepp D. Kohlwein, Maria D. Barrachina, Yulin Liao, Jiankang Chen, Erika Isono, Hugo Seca, Mei Wang, Taras Y. Nazarko, Yannick Bailly, Nadya V. Koshkina, Tapas K. Maiti, Bärbel Rohrer, Karin Nowikovsky, James H. Hurley, Gerald W. Dorn, Nils C. Gassen, Kazuhiro Nagata, Eiki Kominami, A. Ivana Scovassi, Ana Maria Cuervo, Adi Kimchi, Minghua Yang, Sylviane Muller, Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Defense in Plant-Pathogen Interactions [Nagoya, Japan], Nagoya University-Graduate School of Bioagricultural Sciences [Nagoya, Japan], Facultad de Quimica [Santiago], Pontificia Universidad Católica de Chile (UC), Institute of Cancer Sciences [Glasgow, UK] (CR-UK Beatson Institute), University of Glasgow, Cell Death Research & Therapy (CDRT) Lab, Université Catholique de Louvain, Harvard University Statistics Department, Harvard University [Cambridge], Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Conway Institute of Biomolecular and Biomedical Research and School of Chemical and Bioprocess Engineering, University College Dublin [Dublin] (UCD), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biochemistry and Molecular Biology, Thomas Jefferson University-Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University)-Jefferson (Philadelphia University + Thomas Jefferson University), Centro de Estudios Farmacológicos y Botánicos [Buenos Aires] (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Medicina [Buenos Aires], Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA), Thérapie génique, Génomique et Epigénomique (U 1169), Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Department of Experimental Medicine and Public Health, University of Camerino, MRC Toxicology Unit, University of Leicester, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Departamento de Bioquímica y Biología Molecular y Celular, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Department of Pharmaco-Biology, Università della Calabria [Arcavacata di Rende] (Unical), Department of Molecular Genetics [Rehovot, Israël], Weizmann Institute of Science, Fondation Universitaire Notre Dame de la Paix (FUNDP), Facultés Universitaires Notre-Dame de la Paix, Département Advanced Research And Techniques For Multidimensional Imaging Systems (ARTEMIS), Institut Mines-Télécom [Paris] (IMT)-Télécom SudParis (TSP), USC Neuromuscular Center, Department of Neurology, University of Southern California (USC), Centre méditérannéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Giannina Gaslini Institute, Department of Molecular Pharmacology, Albert Einstein College of Medicine, Department of Cancer Biology, University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Inner Mongolia Agricultural University (IMAU), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Indian Institute of Science [Bangalore] (IISc Bangalore), Politecnico di Milano [Milan] (POLIMI), Département des Sciences Biologiques [Montréal], Université du Québec à Montréal (UQAM), Laboratory of Molecular Biology, Scientific Institute E. Medea, Université Catholique de Louvain (UCL), Univ Ancona, Politecn Marche, University of Toronto, Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Department of Clinical and Molecular Medicine, Università degli Studi di Roma 'La Sapienza' [Rome]-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hémato-Cancérologie Expérimentale, CRP-Santé, Dpt of Neuroscience and Brain Technologies [Genova], NeuroEngineering & bio-arTificial Synergic SystemS Laboratory [Genova] (NetS3 Lab), Istituto Italiano di Tecnologia (IIT)-Istituto Italiano di Tecnologia (IIT), Center for Infection and Immunity Amsterdam (CINIMA), Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Régulation de l'expression génétique (REG), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Department of Microbiology and Immunology, Stanford University School of Medicine [CA, USA], Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Department of Dermatology, Brigham and Women's Hospital [Boston], San Raffaele Scientific Institute, Milan, Italy, Laboratory of Molecular Neuroembryology, University of Rome 'Tor Vergeta'-Clinical and Behavioral Neurology - Neuroscienze e riabilitazione, IRCCS Fondazione Santa Lucia [Roma]-Dulbecco Telethon Institute, Department of Pharmacology, Universidade de Santiago de Compostela, Glycobiologie et signalisation cellulaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Complexo Hospitalario Universitario A Coruña, Mécanismes moléculaires de l'angiogénèse, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Florida [Gainesville], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U1172 Inserm), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Centro de Investigaciones Biológicas (CSIC), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Infection bactérienne, inflammation, et carcinogenèse digestive, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Universita degli Studi di Padova, University of British Columbia (UBC), University of Edinburgh, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Australian Regenerative Medicine Institute, Monash University, Clayton, 3800, VIC, Australia, Faculty of Engineering and Natural Sciences, Sabanci University [Istanbul], Department of Biological Sciences [Stanford], Stanford University [Stanford], Université de Montréal (UdeM), Department of Human Genetics, Department of Psychiatry, University of Michigan System-University of Michigan System-Molecular and Behavioral Neuroscience Institute, Centre for Computational and Systems Biology (COSBI), Department of Computer Science [Tsukuba], Graduate School of Systems and Information Engineering [Tsukuba], University of Tsukuba-University of Tsukuba, Institut de biochimie et génétique cellulaires (IBGC), University of Western Ontario (UWO), Genetics, Dynamique Musculaire et Métabolisme (DMEM), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM), Department of Biochemistry and Biophysics, University of Naples Federico II, Lund University [Lund], Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB), Karl-Franzens-Universität Graz, Polytechnic University of Marche, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Cell Biology, Physiology and Immunology, Research Unit on BioActive Molecules, Departamento de Química Orgánica Biológica, Instituto de Investigaciones Quimicas y Ambientales de Barcelona, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), The Buck Institute for Age Research, University of Pisa - Università di Pisa, Laboratorio di Genetica Molecolare, Istituto Gaslini, Universidad de Castilla-La Mancha (UCLM), Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, University of Crete [Heraklion] (UOC), Division of Molecular and Cellular Pathology [Birmingham], Department of Medical Research, Taichung Veterans General Hospital, Modélisation et Simulation Numérique en Mécanique et Génie des Procédés (MSNMGP), Université de la Méditerranée - Aix-Marseille 2-Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), University of Queensland [Brisbane], Dept of Mathematics, Purdue University, Purdue University [West Lafayette], Virologie et Pathologie Humaine (VirPath), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Zhejiang University, Équipe Micro et nanosystèmes HyperFréquences Fluidiques (LAAS-MH2F), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), King Abdullah University of Science and Technology (KAUST), Southern University of Science and Technology of China (SUSTech), OASE, National University of Tainan, Taiwan (OASE), National Taiwan University [Taiwan] (NTU), Weifang Bureau of Land Resources [Weifang], Department of cardiology [Guy's and St. Thomas ' hospitals] [London], Guy's and St Thomas' Hospital [London]-Guy's Hospital [London], University of Pennsylvania [Philadelphia], CRLCC Eugène Marquis (CRLCC), Emory University School of Medicine, Emory University [Atlanta, GA], Korea University, Cytokines et Immunologie des Tumeurs Humaines (U753), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pharmacology [Tartu, Estonie], Institute of Biomedicine and Translational Medicine [Tartu, Estonie], University of Tartu-University of Tartu, Max-Planck-Institut für Biophysikalische Chemie - Max Planck Institute for Biophysical Chemistry [Göttingen], Max-Planck-Gesellschaft, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Cincinnati (UC), Réponses immunes : régulation et développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Experimental Medicine, Oxford University, University of Oxford [Oxford], Division of regenerative Medicine, San Raffaele Scientific Institute, The University of New Mexico [Albuquerque], Université Libre de Bruxelles [Bruxelles] (ULB), Macrophages et Développement de l'Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Scienze Biomediche, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Department of Experimental Medicine and Oncology, University of Turin, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), CNV, University of Valparaiso, Institut Gustave Roussy (IGR), Universidad Autonoma de Madrid (UAM), Cell Signalling & Proteomics Group [Londres, Royayme-Uni], Barts Cancer Institute [Londres, Royayme-Uni], Queen Mary University of London (QMUL)-Queen Mary University of London (QMUL), Department of General, Visceral and Vascular Surgery [Jena], Friedrich-Schiller-Universität Jena, Department of Biomedical Engineering, The University of Texas at Austin, University of Texas at Austin, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Fondazione Santa Lucia (IRCCS), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jacques Monod (IJM (UMR_7592)), Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Department of Biology, Johns Hopkins University (JHU), Neurogenetics Group, Instituto de Investigación en Recursos Cinegéticos (IREC), Laboratório de Ultraestrutura Celular Hertha Meyer (IBCCF), Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Molecular and Cellular Biology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), National University of Ireland [Galway] (NUI Galway), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Freiburg Institute for Advanced Studies-LifeNet, Albert-Ludwigs-Universität Freiburg, Groupe de Recherche en Immunopathologies et maladies infectueuses (GRI), Université de La Réunion (UR)-Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Brunel University London [Uxbridge], Unité Propre de Recherche 2357, Institution de Biologie Moléculaire des Plantes, Radiothérapie moléculaire (UMR 1030), Department of Chemistry, University of Kentucky, Universidad de Córdoba [Cordoba], Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' [Rome], Facultad de Ciencias Químicas y Farmacéuticas, Centro de Estudios Moleculares de la Célula, Biochemistry and Molecular Biology, Goethe-University Frankfurt am Main, Department of Biological and Environmental Sciences and Technologies (DiSTeBA), Università del Salento, Institut Bergonié - Département de médecine, Université Bordeaux Segalen - Bordeaux 2-Centre régional de lutte contre le cancer [CRLCC], Institut National Polytechnique de Lorraine (INPL), Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de signalisation moléculaire et neurodégénerescence, Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Européen de Chimie et Biologie (IECB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Trafic membranaire et Division cellulaire, Landesbetrieb Hessisches Landeslabor, Hematology-Oncology Division, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], University of Pavia, Instituto de Investigaciones Biotecnológicas [San Martín] (IIB-INTECH), Universidad Nacional de San Martin (UNSAM)-Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), University of Helsinki, School of Physics and Astronomy [Exeter], University of Exeter, Department of Biomedicinal Chemistry (CSIC), Institut de Química Avançada de Catalunya, Laboratory of Vascular Pathology (IDI-IRCCS), Istituto Dermopatico dell'Immacolata, Peking University [Beijing], MRC Centre for Developmental Neurobiology, University of Brescia, Immunobiologie fondamentale et clinique, Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC régional épidémiologie clinique/essais cliniques - Ile de la Réunion (CIC-EC), University of Rome 'Tor Vergeta', Universidad de Oviedo [Oviedo], Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Dulbecco Telethon Institute/Department of Biology, Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), Rockefeller University [New York], The Babraham Institute, Kansas State University, McGill University, Service d'Anatomie et Cytologie Pathologique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Department of Medicine [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), ATOS Origin, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences-Tohoku University [Sendai], Goethe-University, Goethe-Universität Frankfurt am Main, Institute of physiological chemistry, Hannover Medical School [Hannover] (MHH), Department of Physiology, Department of Plant and Environmental Sciences, Apoptose, cancer et immunité (U848), Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Departments of Neurology and Psychiatry, Alzheimer's Disease Research Center, Institute of Experimental Immunology - IEI [Zürich, Switzerland], Université de Zurich [Switzerland], Digital Enterprise Research Institute (DERI-NUIG), Spanish National Research Council (CSIC), Cell Death Research and Therapy Unit [Leuven, Belgium] ( Department of Cellular and Molecular Medicine), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCINA - Département ONCO - Equipe 15), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Department of Medicine [San Francisco], University of California [San Francisco] (UCSF), University of California-University of California, Fondazione Santa Lucia [IRCCS], Clinical and Behavioral Neurology [IRCCS Santa Lucia], Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Department of Anatomy, Histology, Forensic Medicine and Orthopedic, N.A., Division of Pharmacology and Chemotherapy, Department of Internal Medicine, Pathogénie Microbienne Moléculaire, University of Chile [Santiago], Université de Montpellier (UM), Faculdade de Ciências Farmacêuticas de Ribeirão Preto [São Paulo], Universidade de São Paulo (USP), Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Catalan Institute of Oncology, Department of Cell Biology, National Institute for Basic Biology [Okazaki], Instituto de Bioquímica Vegetal y Fotosíntesis (IBVF), Universidad de Sevilla-Centro de Investigaciones Científicas Isla de la Cartuja, The Adams Super Center for Brain Studies, Tel Aviv University [Tel Aviv], Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Department of Pharmacology and biochemistry, Virginia Commonwealth University (VCU), Department of Immunology, St Jude Children's Research Hospital, Department of Biology and Biotechnologies 'Charles Darwin', Lettres, Idées, Savoir (LIS), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institute of Biological Chemistry and Nutrition, University of Hohenheim, China Seismological Bureau, Massachusetts Institute of Technology (MIT), Rosenstiel Basic Medical Sciences Research Center [Waltham], Brandeis University, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), Meakins-Christie Laboratories, Sanford Burnham Medical Research Institute, La Jolla, National Institute of Advanced Industrial Science and Technology (AIST), ORIENT ET MÉDITERRANÉE : Textes, Archéologie, Histoire (OM), Université Panthéon-Sorbonne (UP1)-École pratique des hautes études (EPHE)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Centro de Investigacion y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Biochemistry and Molecular Biology I, Department of Immunology and Infectious Diseases, Harvard School of Public Health, aDepartment of Plant Biology, Uppsala BioCenter, Swedish University of Agricultural Sciences (SLU), Philipps University of Marburg, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Renal Division, University Medical Center Freiburg, Freiburg, Germany, Rural Health Academic Centre, University of Melbourne-Rural Clinical School, Department of Pathology, University of Veterinary and Animal Sciences, Dipartimento di Scienze della Vita [Modena, Italy], Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pathology, Anatomy & Cell Biology [Philadelphia, Pennsylvania, USA], Thomas Jefferson University, Department of Molecular Neuroscience, Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Centro de Investigación en Bioquímica Clínica e Inmunología (CONICET), Universidad Nacional de Córdoba, Córdoba, Argentina, Neuroinflammation Unit, Biotech Research and Innovation Centre-University of Copenhagen = Københavns Universitet (KU), Mathematics and Computing in Automatic Control and Optimization for the User (MIAOU), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Danish Cancer Society, Institute of Cancer Biology, UCL-Institute of Child Health (ICH), Institute of Child Health-Great Ormond Street Hospital for Children [London] (GOSH), Division of Renal Diseases and Hypertension, University of Colorado [Boulder], Institut de biologie et chimie des protéines [Lyon] (IBCP), Joslin Diabetes Center, Universität Ulm - Ulm University [Ulm, Allemagne], Qingdao Institute of Marine Geology, China Geological Survey, Qingdao 266071, China, Université Paris Diderot - Paris 7 (UPD7), Institute of Software, Chinese Academy of Sciences [Beijing] (CAS), Metabolic Engineering Group, Departamento de Microbiologia y Genetica, Edificio Departamental, Campus Miguel de Unamuno, Universidad de Salamanca, University of Minnesota [Twin Cities], University of Minnesota System, Department of Cellular and Molecular Physiology, Yale University School of Medicine, The Arctic University of Norway, Department of Biological Sciences, The Open University [Milton Keynes] (OU), Summit Analytical, CALRG, Institute of Educational Technology, Institute for Neurologic Disabilities Research, Faculty of Health Sciences-University of Pretoria [South Africa], Department of Paediatric Neurology, Guy's and St Thomas' Hospital [London]-Evelina Children's Hospital, Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Dana-Farber Cancer Institute and the Department of Cell Biology, Harward Medical School, Translational Health Science and Technology Institute [Faridabad] (THSTI), Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, School of Reliability and Systems Engineering [Beijing], Beihang University, Oxford Centre for Integrative Systems Biology, Center for Membrane and Cell Physiology [Charlottesville, VA, USA] (School of Medicine), University of Virginia [Charlottesville], Apoptose, cancer et immunité (Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Karlsruher Institut für Technologie (KIT), Faculty of Pharmaceutical Sciences, Hokkaido University, École normale supérieure - Paris (ENS Paris), School of Electrical Engineering [Seoul] (Korea University), Department of Mathematics and Statistics [Guelph], University of Guelph, Department of Molecular Genetics, Department of Genetics [Stanford, CA, États-Unis], Institute of Immunology, University Hospital Schleswig-Holstein, Arizona Respiratory Center, Okazaki Institute for Integrative Bioscience, ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Newcastle University [Newcastle], JRC Institute for Transuranium Elements [Karlsruhe] (ITU ), European Commission - Joint Research Centre [Karlsruhe] (JRC), Department of Neuroscience, University of Texas Southwestern Medical Center [Dallas], Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Laboratory of Functional Neurogenomics [Tuebingen, Germany], University of Tuebingen-Center of Neurology and Hertie-Institute for Clinical Brain Research [Tuebingen, Germany], Indian Institute of Technology Bombay (IIT Bombay), European Organization for Nuclear Research (CERN), Harvard Medical School [Boston] (HMS), Indian School of Mines, Department of Computer Science [UIUC] (UIUC), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System-University of Illinois System, Centre for Cancer Biology, Hanson Institute, Adelaide, University of California [San Diego] (UC San Diego), University of California, Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Biochemistry, University of Bristol, Organisation Nucléaire et Oncogenèse, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), FONDAP Center CEMC Estudios Moleculares de la Célula, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Chungnam National Univesity School of Medicine, Taejon, Korea, Chungnam National Univesity School of Medicine, Micro & Nanobiotechnologies, Institut des Sciences Analytiques (ISA), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Center for Applied Mathematics, Tsinghua University [Beijing], University of Connecticut School of Medicine, University of Connecticut (UCONN), Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes (LBMCE), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Microenvironnement et Physiopathologie de la Differenciation, Division of Nephrology and Hypertension, Mayo Clinic, Beatson Institute for Cancer Research, Beatson institute for cancer research, Howard Hughes Medical Institute, Howard Hugues Medical Institute, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Computing Technology [Beijing] (ICT), Chinese Academy of Sciences [Changchun Branch] (CAS), School of Electronics and Computer Science (ECS), University of Southampton, Third Hospital, Department of Anesthesiology, Cognitive Interaction Technology [Bielefeld] (CITEC), Universität Bielefeld = Bielefeld University, Procédés, Matériaux et Energie Solaire (PROMES), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Faculty of Pharmacy- University of Coimbra, National Neuroscience Institute, Key Laboratory of Molecular Virology & Immunology (LMVI), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Coll Life Sci, Beijing Normal University, Delft University of Technology (TU Delft), Christian-Albrechts-Universität zu Kiel (CAU), Department of Molecular Pathology and Microbiology, Center for Applied Proteomics and Molecular Medicine-George Mason University [Fairfax], Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University), Institut des Sciences Chimiques de Rennes (ISCR), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Rennes-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Department of Chemistry, University of Pittsburgh, University of Pittsburg, Tianjin University of Science and Technology (TUST), Hunan University of Science and Technology [Xiangtan], Laboratoire de Génie Civil et Génie Mécanique (LGCGM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), China Agricultural University (CAU), Acad Disaster Reduct and Emergency Management, Minist Civil Affairs, Minist Educ, Beijing, Peoples R China, affiliation inconnue, Département Technologie des Polymères et Composites & Ingénierie Mécanique (TPCIM), École des Mines de Douai (Mines Douai EMD), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Ministère de l'Economie, des Finances et de l'Industrie, MOE Key Laboratory of Bioinformatics, Centre for Plant Biology, School of Life Sciences, Laboratoire d'Informatique Gaspard-Monge (ligm), Université Paris-Est Marne-la-Vallée (UPEM)-École des Ponts ParisTech (ENPC)-ESIEE Paris-Fédération de Recherche Bézout-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie Moléculaire et Cellulaire (LBMC), Université de Bourgogne (UB), Center for International Blood and Marrow Transplant Research (CIBMTR), Emory University [Atlanta, GA]-Medical College of Wisconsin, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Illman Cancer Center, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Ingénierie des Matériaux Polymères (IMP), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Department of Medical Microbiology and Immunology, University of California [Davis] (UC Davis), School of Health Sciences, University of Minho [Braga], Équipe Calcul Distribué et Asynchronisme (LAAS-CDA), University of California [Riverside] (UCR), Ohio State University [Columbus] (OSU), Laboratory of Systems Biology, Van Andel Institute [Grand Rapids], Division of Genetics and Cell Biology, National Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Oregon Health and Science University [Portland] (OHSU), Dendrite Differenciation Group [DZNE - Bonn], German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Equipe 12, Génétique moléculaire, signalisation et cancer (GMSC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Medical Center [Utrecht], Institut d'Investigacions Biomèdiques August Pi I Sunyer [Barcelona, Spain] (Hospital Clinic ), Department of Genetics, Trinity College Dublin, Fisiopatologia de los procesos inflamatorios, Vall d'Hebron Research Institute, Institució Catalana de Recerca i Estudis Avançats (ICREA), Department of Human Genetics, Nagasaki University, Transduction du signal et oncogénèse, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie, Center for Experimental and Molecular Medicine, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Department of medical Biochemistry, University of Amsterdam [Amsterdam] (UvA), IDI-IRCCS Biochemistry Laboratory, Università degli Studi di Roma Tor Vergata [Roma], Program Against Cancer Therapeutic Resistance/Metabolism & Cancer Group [Catalonia, Spain] (ProCURE), Catalan Institute of Oncology-Girona (ICO-Girona), Instituto de Tecnologia Química e Biológica António Xavier (ITQB), Universidade Nova de Lisboa (NOVA), Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza Hospital, CNR, Consiglio Nazionale delle Ricerche (CNR), Biochimie et Physiologie Moléculaire des Plantes (BPMP), Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, The Hospital for sick children [Toronto] (SickKids), Universidad de Sevilla, Immunité muqueuse et vaccination, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR50-Université Nice Sophia Antipolis (... - 2019) (UNS), DIMS, University of Trento [Trento], Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Department of Cellular and Molecular Medicine [Madrid, Spain], Laboratory of Cell Death and Cancer Therapy [Madrid, Spain], Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC) -Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth PL1 3HD, UK, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dpt. of Cancer & Cell Biology, Interactions Bactéries-Cellules (UIBC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Max planck Institute for Biology of Ageing [Cologne], Euromov (EuroMov), Wellcome Trust Centre for Molecular Parasitology [Glasgow, UK], University of Glasgow- Institute of Infection, Immunity and Inflammation [Glasgow, UK], Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), UMR 1599, Centre National de la Recherche Scientifique (CNRS), EA 4100, Histoire culturelle et sociale de l'art (HiCSA), Université Panthéon-Sorbonne (UP1)-Université Panthéon-Sorbonne (UP1), Centre for Astrophysics and Supercomputing (Centre for Astrophysics and Supercomputing), Swinburne University of Technology [Melbourne], Department of Cellular and Physiological Sciences [Vancouver, BC, Canada] (Life Sciences Institute), University of British Columbia (UBC)-Life Sciences Institute [Vancouver, BC, Canada], School of Pharmacy, Department of Experimental Medicine, Dept. Neurosciences, Department of Internal Medicine, Radboud University Medical Center [Nijmegen], Institute of Medical Genetics and Applied Genomics, Radiation Physics, School of Life Science, Department of Basic Biology, The Graduate University for Advanced Studies, CIBER de Enfermedades Neurodegenerativas (CIBERNED), Doshisha University, National Cancer Research Center [Tokyo, Japan], University of Washington [Seattle], Department of Experimental Neurodegeneration [Göttingen, Germany], University Medical Center Göttingen (UMG), Cibles moléculaires et thérapeutiques de la maladie d'Alzheimer (CIMoTHeMA), Université de Poitiers, Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), BioCeV-Institute of Microbiology, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto di chimica biologica, Università degli Studi di Verona, Département Image et Traitement Information (ITI), Institut Mines-Télécom [Paris] (IMT)-Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne, Department of Cell Biology and Biophysics, Università degli Studi di Firenze [Firenze], Cell Immunity in Cancer, Inflammation and infection Group [Zaragoza, Spain] (Biomedical Research Center), Nanoscience Institute of Aragon - INA [Zaragoza, Spain]-Fundación Agencia Aragonesa para la Investigación y el Desarrollo - ARAID [Zaragoza, Spain]-University of Zaragoza - Universidad de Zaragoza [Zaragoza], Department of Pediatrics, Università degli studi di Napoli Federico II, Transfert de Genes a Visee Therapeutique Dans les Cellules Souches, Developpement Normal et Pathologique du Système Immunitaire, Signalisation et physiopathologie des cellules épithéliales, Facultad de Medicina, Universidad de Santiago de Chile [Santiago] (USACH), Departamento de Farmacobiología, Cinvestav-Sede Sur, Centre de recherche Croissance et signalisation (UMR_S 845), College of Life Sciences, Central China Normal University, Institute of Molecular Biotechnology, Austrian Academy of Sciences (OeAW), Laboratory of Cardiac Surgical Research, Monash University [Clayton], Universidade do Minho, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Neurodegenerative Diseases Research Group (CIBERNED), Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases, Barcelona, Department of medicine, Syracuse, NY, USA, State University of New York (SUNY), National University of Singapore (NUS)-Yong Loo Lin School of Medicine-Graduate School for Integrative Sciences and Engineering, McGill University Health Center [Montreal] (MUHC), National Institute for Infectious Diseases, Transporteurs en Imagerie et Radiothérapie en Oncologie (TIRO - UMR E4320), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biomedical Sciences, Department of Genetics of Eukaryotic Microorganisms, Georg-August-University [Göttingen]-Institute of Microbiology and Genetics, Sterol metabolism and therapeutic innovations in oncology, Institut Claudius Regaud, CRLCC Institut Claudius Regaud-CRLCC Institut Claudius Regaud-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Department of Molecular, Cellular and Developmental Biology, Señalización Celular 4, Institute of integrative biology (Liverpool), University of Liverpool, Department of Human Biology, University of Cape Town, National Institute of Diabetes and Digestive and Kidney Diseases [Bethesda], Department of Molecular Biology, Eberhard Karls Universität Tübingen, Technical University of Munich (TUM), Biophysics and Bioinformatics Laboratory, Department of Cell Biology and Morphology, Université de Lausanne (UNIL), Shenyang Institute of Automation, the Chinese Academy of Sciences (SIA), Key Laboratory of Thermo-Fluid Science and Engineering of Ministry of Education, Xi'an Jiaotong University (Xjtu), Dipartimento di Biologia, Mechanics laboratory , UniversityAmar Telidji, 3000 Laghouat, Algéria., Mechanics laboratory , University Amar Telidji, sans affiliation, Service d'hépatologie [Hôpital Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), University of Waterloo, Waterloo, ON, Canada, Institute of Cell Biology and Immunology, University of Stuttgart, Chaperones Research Group, Institute of Biosciences and Technology [Houston, TX, États-Unis] (IBT), Texas A&M Health Science Center [Houston, TX, États-Unis] (TAMHSC), Texas A&M University Health Science Center-Texas A&M University Health Science Center, Aquatic and Crop Resource Development, National Research Council of Canada (NRC), Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche [Ancona] (UNIVPM), Department of Biochemistry and Molecular Biology [Indianapolis, IN, USA], Indiana University School of Medicine, Indiana University System-Indiana University System, Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, iMed.UL, Faculty of Pharmacy, University of Lisbon, CESAM & Biology Department, Universidade de Aveiro, Celullar and Molecular Medicine, Università degli Studi di Perugia (UNIPG), Institute of Clinical Molecular Biology, Kiel University, Apoptose et Système Immunitaire (ASI), Vieillissement Cellulaire Intégré et Inflammation (VCII), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Mathematical Sciences [Aalborg], Aalborg University [Denmark] (AAU), Cambridge Institute for Medical Research (CIMR), University of Cambridge [UK] (CAM), Biozentrum, University of Basel (Unibas), Structural and Computational Biology Unit, European Molecular Biology Laboratory [Grenoble] (EMBL), Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers), Université de Perpignan Via Domitia (UPVD), Universidad Pablo de Olavide [Sevilla] (UPO), Department of Neurosciences, Agronomes et Vétérinaires Sans Frontières (AVSF), AVSF, Department of Mathematics [Gakushuin], Gakushuin University, Department of Internal Medicine [Münster, Germany], University of Münster, Neurogenetics laboratory, University Medicine Goettingen, Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université d'Uruguay, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Institute for Conservation & Improvement of Valentian Agrodiversity (COMAV), Universitat Politecnica de Valencia (UPV), ICBM, University of Chile [Santiago]-Faculty of Medicine, Nutrition, Métabolisme, Aquaculture (NuMéA), Institut National de la Recherche Agronomique (INRA)-Université de Pau et des Pays de l'Adour (UPPA), Department of Cell Biology, Baltimore, Johns Hopkins University School of Medicine, Baylor College of Medicine (BCM), Baylor University, University of Minnesota Medical School, Beijing Candid soft Technology Co. Ltd, Nanjing University of Information Science and Technology, Department of Hepatobiliary and Pancreatic Surgery [Maebashi, Japan], Gunma University Graduate Schoolof Medicine [Maebashi, Japan], Department of Molecular Genetics [Maastricht, The Netherlands], Maastricht University [The Netherlands], Institute of Cell Biology and Genetic Engineering, National Academy of Sciences of Ukraine (NASU), Institute of Pharmacology of Natural Products and Clinical Pharmacology, Institute of Pharmacology, University of Bern, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Wilmer Eye Institute, Mayo Clinic and Mayo College of Medicine, Rochester, Institute of Biochemistry and Biophysics, Polska Akademia Nauk (PAN)-Sciences, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], Department of Chemistry and Toxicology, Norwegian Veterinary Institute, Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center [Houston], University of Minho, Friedrich Miescher Laboratory (FML), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Department of Biomedical Sciences and Biotechnologies, Brescia University, Department of Physiological Chemistry [Bochum], Ruhr-Universität Bochum [Bochum], University of Oslo (UiO), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Facultés Universitaires Notre Dame de la Paix (FUNDP), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226, Université du Québec à Montréal = University of Québec in Montréal (UQAM), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Université Lille 2 - Faculté de Médecine -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées, Université libre de Bruxelles (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidade Federal do Rio de Janeiro (UFRJ), Institut Bergonié [Bordeaux], UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Trafic membranaire et Division cellulaire - Membrane Traffic and Cell Division, Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Sud - Paris 11 (UP11), McGill University = Université McGill [Montréal, Canada], Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Signaling in Oncogenesis, Angiogenesis and Permeability (CRCINA-ÉQUIPE 15), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Universidad de Chile = University of Chile [Santiago] (UCHILE), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISC), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Université Panthéon-Sorbonne (UP1)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Collège de France (CdF (institution)), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Great Ormond Street Hospital for Children [London] (GOSH)-Institute of Child Health, Hokkaido University [Sapporo, Japan], Université Paris sciences et lettres (PSL), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Lyon-Université de Lyon, Centre d’Infection et d’Immunité de Lille (CIIL) - INSERM U1019 - UMR 9017 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Organisation Nucléaire et Oncogenèse - Nuclear Organization and Oncogenesis, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon], Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), The Beatson Institute for Cancer Research, Beijing Normal University (BNU), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Bézout-ESIEE Paris-École des Ponts ParisTech (ENPC)-Université Paris-Est Marne-la-Vallée (UPEM), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon], Vall d’Hebron Research Institute (VHIR), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade Nova de Lisboa = NOVA University of Lisboa (NOVA), Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Doshisha University [Kyoto], Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Università degli Studi di Firenze = University of Florence [Firenze], University of Zaragoza - Universidad de Zaragoza [Zaragoza]-Nanoscience Institute of Aragon - INA [Zaragoza, Spain]-Fundación Agencia Aragonesa para la Investigación y el Desarrollo - ARAID [Zaragoza, Spain], Central China Normal University [Wuhan, China], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-UMR E4320 (TIRO-MATOs), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Claudius Regaud, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de biologie structurale [1992-2019] (IBS - UMR 5075 [1992-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Nanjing University of Information Science and Technology (NUIST), Facultad de Medicina [Buenos Aires], Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA)-Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Clermont Auvergne (UCA)-Institut National de la Recherche Agronomique (INRA), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Universidad Nacional de San Martin (UNSAM), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, George Mason University [Fairfax]-Center for Applied Proteomics and Molecular Medicine, Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institute of Infection, Immunity and Inflammation [Glasgow, UK]-University of Glasgow, Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Settore BIO/06, biology, Cell Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, biology.organism_classification, Cell biology, Interpretation (model theory), 03 medical and health sciences, Arama, 030104 developmental biology, Molecular Biology, Humanities, ComputingMilieux_MISCELLANEOUS
Abstract: Author(s): Klionsky, DJ; Abdelmohsen, K; Abe, A; Abedin, MJ; Abeliovich, H; Arozena, AA; Adachi, H; Adams, CM; Adams, PD; Adeli, K; Adhihetty, PJ; Adler, SG; Agam, G; Agarwal, R; Aghi, MK; Agnello, M; Agostinis, P; Aguilar, PV; Aguirre-Ghiso, J; Airoldi, EM; Ait-Si-Ali, S; Akematsu, T; Akporiaye, ET; Al-Rubeai, M; Albaiceta, GM; Albanese, C; Albani, D; Albert, ML; Aldudo, J; Algul, H; Alirezaei, M; Alloza, I; Almasan, A; Almonte-Beceril, M; Alnemri, ES; Alonso, C; Altan-Bonnet, N; Altieri, DC; Alvarez, S; Alvarez-Erviti, L; Alves, S; Amadoro, G; Amano, A; Amantini, C; Ambrosio, S; Amelio, I; Amer, AO; Amessou, M; Amon, A; An, Z; Anania, FA; Andersen, SU; Andley, UP; Andreadi, CK; Andrieu-Abadie, N; Anel, A; Ann, DK; Anoopkumar-Dukie, S; Antonioli, M; Aoki, H; Apostolova, N; Aquila, S; Aquilano, K; Araki, K; Arama, E; Aranda, A; Araya, J; Arcaro, A; Arias, E; Arimoto, H; Ariosa, AR; Armstrong, JL; Arnould, T; Arsov, I; Asanuma, K; Askanas, V; Asselin, E; Atarashi, R; Atherton, SS; Atkin, JD; Attardi, LD; Auberger, P; Auburger, G; Aurelian, L; Autelli, R
Published: 2016
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43. Phase I evaluation of the effects of ketoconazole and rifampicin on cediranib pharmacokinetics in patients with solid tumours

Author: James Spicer, Tim Meyer, R. Rafi, Michael B. Sawyer, Ulrik Lassen, Wilson H. Miller, D. Adamson, E. Chen, Kathryn H. Brown, Dorte Nielsen, Sebastien J. Hotte, Thomas J. Evans, and Christian K. Kollmansberger
Subjects: Adult, Cancer Research, medicine.drug_class, Pharmacology, Toxicology, Tyrosine-kinase inhibitor, Cediranib, Young Adult, Pharmacokinetics, Neoplasms, Cytochrome P-450 CYP3A, Humans, Medicine, Drug Interactions, Pharmacology (medical), In patient, Aged, CYP3A4, business.industry, Middle Aged, Safety profile, Ketoconazole, Receptors, Vascular Endothelial Growth Factor, Oncology, Area Under Curve, Quinazolines, Cytochrome P-450 CYP3A Inhibitors, Rifampin, business, Rifampicin, medicine.drug
Abstract: To investigate any effect of a CYP3A4 inhibitor (ketoconazole) or inducer (rifampicin) on cediranib steady-state pharmacokinetics in patients with advanced solid tumours. In two Phase I, open-label trials, patients received once-daily oral doses of cediranib alone [20 mg (ketoconazole study); 45 mg (rifampicin study)] for 7 days followed by cediranib at the same dose with ketoconazole 400 mg/day for 3 days or once-daily rifampicin 600 mg/day for 7 days, respectively. Patients then continued to receive once-daily cediranib. In the ketoconazole study, 46 patients were dosed; 38 were evaluable for C ss,max, 36 for AUCss. gMean AUCss and C ss,max for cediranib 20 mg increased by 21 % (94 % CI 9–35 %) and 26 % (94 % CI 10–43 %), respectively, in the presence of ketoconazole. In the rifampicin study, 64 patients were dosed; 44 were evaluable for C ss,max and 41 for AUCss. gMean AUCss and C ss,max for cediranib 45 mg decreased by 39 % (90 % CI 34–43 %) and 23 % (90 % CI 16–30 %), respectively, in the presence of rifampicin. gMean ratios for AUCss and C ss,max were >1 for ketoconazole and
Published: 2012
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44. Management of suspected Lyme borreliosis: experience from an outpatient parenteral antibiotic therapy service

Author: Beth White, Thomas J. Evans, and R.A. Seaton
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Cost-Benefit Analysis, Neutropenia, Young Adult, Lyme disease, Outpatients, Ambulatory Care, Humans, Medicine, Young adult, Infusions, Intravenous, Intensive care medicine, Adverse effect, Home Infusion Therapy, Aged, Retrospective Studies, Aged, 80 and over, Lyme Disease, Evidence-Based Medicine, business.industry, Retrospective cohort study, General Medicine, Evidence-based medicine, Middle Aged, medicine.disease, Anti-Bacterial Agents, Clinical trial, Treatment Outcome, Scotland, Practice Guidelines as Topic, Female, Liver function, business
Abstract: Objectives: Lyme borreliosis (LB) is the most common human tick-borne infection in Europe and the USA. In this study we set out to analyse the outcome of patients treated for Lyme disease via outpatient parenteral antibiotic therapy (OPAT) and the appropriateness of this treatment using current guidelines. Methods: This was a retrospective review of all patients with suspected LB managed via OPAT in Glasgow in 2000–11. Results: Of 72 patients treated for suspected LB, 35 patients (49%) were treated in accordance with guidelines and 36 (50%) were treated with no specific guidelines. A definite improvement was seen in 20 patients (28%). Adverse reactions were documented in 29 (40%) patients with neutropenia, and mild liver function derangement was most commonly observed. Conclusions: These results show the complexity of translating well-substantiated regimens from clinical trials to actual clinical practice. OPAT was an effective way of administering parenteral therapy for Lyme disease but should not be undertaken lightly due to the rate of adverse events and low rates of success in certain patient groups seen in this study. In view of this, stricter criteria for inclusion to OPAT in line with published guidance should be applied to minimize patient harm and optimize success.
Published: 2012
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45. A phase I and pharmacokinetic study of elisidepsin (PM02734) in patients with advanced solid tumors

Author: M. Cullell-Young, Thomas J. Evans, Ana Oaknin, M. Gil, C. Coronado, D. Crawford, C. Cuadra, Ramon Salazar, Arturo Soto-Matos, Robert Jones, J. L. Iglesias Dios, and Carol Hopkins
Subjects: Adult, Male, Elisidepsin, Cancer Research, medicine.medical_specialty, Maximum Tolerated Dose, Urology, Antineoplastic Agents, Pharmacology, Toxicology, Transaminase, Pharmacokinetics, Refractory, Depsipeptides, Neoplasms, medicine, Humans, Pharmacology (medical), Infusions, Intravenous, Transaminases, Aged, Body surface area, Dose-Response Relationship, Drug, business.industry, Middle Aged, Clinical trial, Treatment Outcome, Oncology, Cohort, Toxicity, Disease Progression, Female, business
Abstract: To determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and recommended phase II dose (RD) of elisidepsin.Eligible patients with refractory, advanced solid tumors received elisidepsin as 24-h intravenous infusion every 3 weeks. Pharmacokinetic profiles were analyzed during cycles 1 and 2.Forty-two patients received elisidepsin at doses from 0.5 to 6.8 mg/m(2). The MTD was 6.8 mg/m(2), and the RD was 5.5 mg/m(2). Cohort expansion at the RD was done at a fixed dose (FD) of 10 mg, considered equivalent to 5.5 mg/m(2). DLTs (reversible grade 3 transaminase increases) occurred at 6.8 mg/m(2) (n = 2 patients), 5.5 mg/m(2) (n = 1), and 10 mg FD (n = 1). One patient with esophageal adenocarcinoma achieved complete response for38 months, and 12 patients had disease stabilization (8 for ≥3 months). Median time-to-progression for these 12 patients was 4.8 months. Plasma elisidepsin concentrations increased with dose. No drug accumulation between cycles was found. No correlation was observed between body surface area (BSA) and plasma clearance; therefore, elisidepsin was given as flat dose (in mg) in the expansion cohort at the RD and in ongoing clinical trials.Elisidepsin is well tolerated with predictable reversible transaminase increases. Encouraging preliminary evidence of antitumor activity was observed.
Published: 2012
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46. Investigating the potential use of aerial line transect surveys for estimating polar bear abundance in sea ice habitats: A case study for the Chukchi Sea

Author: Ryan M. Nielson, Michelle Bourassa Stahl, and Thomas J. Evans
Subjects: geography, Distance sampling, geography.geographical_feature_category, biology, Ursus maritimus, Ecology, Ratio estimator, Aquatic Science, Survey methodology, Habitat, Abundance (ecology), biology.animal, Sea ice, Environmental science, Physical geography, Transect, Ecology, Evolution, Behavior and Systematics
Abstract: The expense of traditional capture-recapture methods, interest in less invasive survey methods, and the circumpolar decline of polar bear (Ursus maritimus) habitat require evaluation of alternative methods for monitoring polar bear populations. Aerial line transect distance sampling (DS) surveys are thought to be a promising monitoring tool. However, low densities and few observations during a survey can result in low precision, and logistical constraints such as heavy ice and fuel and safety limitations may restrict survey coverage. We used simulations to investigate the accuracy and precision of, DS for estimating polar bear abundance in sea ice habitats, using the Chukchi Sea subpopulation as an example. Simulation parameters were informed from a recent pilot survey. Predictions from a resource selection model were used for stratification, and we compared two ratio estimators to account for areas that cannot be sampled. The ratio estimator using predictions of resource selection by polar bears allowed for extrapolation beyond sampled areas and provided results with low bias and CVs ranging from 21% to 36% when abundance was >1,000. These techniques could be applied to other DS surveys to allocate effort and potentially extrapolate estimates to include portions of the landscape that are logistically impossible to survey.
Published: 2012
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47. A phase I study of E7080, a multitargeted tyrosine kinase inhibitor, in patients with advanced solid tumours

Author: William Copalu, A. Mazur, Jantien Wanders, M Keesen, R. Morrison, D. S. Boss, Jos H. Beijnen, J P O'Brien, Jan H.M. Schellens, Hilary Glen, Thomas J. Evans, and B Tait
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Maximum Tolerated Dose, medicine.drug_class, Biology, Tyrosine-kinase inhibitor, Internal medicine, Neoplasms, Protein-Tyrosine Kinases, medicine, Humans, In patient, Protein Kinase Inhibitors, solid tumours, Aged, Aged, 80 and over, Phenylurea Compounds, receptor tyrosine kinase inhibitor, phase I, Middle Aged, Phase i study, Clinical trial, Endocrinology, Oncology, Maximum tolerated dose, dose escalation, Cancer research, Clinical Study, Quinolines, E7080, Female, pharmacokinetics
Abstract: Background: The objectives of this phase I study were to assess the safety and tolerability of E7080 in patients with advanced, refractory solid tumours; to determine the maximum tolerated dose (MTD) and pharmacokinetics profile of E7080; and to explore preliminary evidence of its anti-tumour efficacy. Methods: E7080 was administered orally in escalating doses on a once-daily continuous schedule in 28-day cycles to eligible patients. Samples for pharmacokinetic analyses were collected on days 1, 8, 15 and 22 of cycle 1 and day 1 of cycle 2. Anti-tumour efficacy was assessed every two cycles. Results: Eighty-two patients received E7080 in dose cohorts from 0.2 to 32 mg. Dose-limiting toxicities were grade 3 proteinuria (two patients) at 32 mg, and the MTD was defined as 25 mg. The most frequently observed cumulative toxicities (all grades) were hypertension (40% of patients), diarrhoea (45%), nausea (37%), stomatitis (32%) and vomiting (23%). Seven patients (9%) had a partial response and 38 patients (46%) had stable disease as best response. E7080 has dose-linear kinetics with no drug accumulation after 4 weeks' administration. Conclusion: E7080 is well tolerated at doses up to 25 mg per day. Encouraging anti-tumour efficacy was observed in patients with melanoma and renal cell carcinoma.
Published: 2012

48. What is different about serotype 1 pneumococci?

Author: Timothy J. Mitchell, Thomas J. Evans, and Neil D. Ritchie
Subjects: Microbiology (medical), Serotype, Bacterial capsule, Pneumolysin, Virulence Factors, Outbreak, Biology, medicine.disease, medicine.disease_cause, Microbiology, Virology, Asymptomatic, Pneumococcal Infections, Pneumococcal infections, Streptococcus pneumoniae, Antigen, medicine, Animals, Humans, medicine.symptom, Africa South of the Sahara, Bacterial Capsules
Abstract: Serotype 1 Streptococcus pneumoniae is among the most commonly isolated serotype in invasive pneumococcal disease but is rarely found causing asymptomatic nasopharyngeal colonization. Compared to infection by other serotypes, infection caused by serotype 1 is more likely to be identified in young patients without comorbidities but is generally associated with a lower mortality. Empyema and extrapulmonary manifestations are common. Outbreaks of serotype 1 disease have been reported in closed communities and epidemics are particularly common in sub-Saharan Africa. The serotype 1 capsular polysaccharide is a zwitterionic structure that enables it to function as a T-cell dependent antigen under some circumstances, in contrast to other pneumococcal capsular polysaccharides that are T-cell independent antigens. There are also differences in the key virulence factor pneumolysin in some serotype 1 isolates. The clinical significance of these differences remains to be determined.
Published: 2012
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49. Temporal trends of Hg in Arctic biota, an update

Author: Thomas J. Evans, Kurunthachalam Kannan, Maria Dam, Derek C. G. Muir, Jon Aars, Christian Sonne, Norman Whitaker Green, Anders Bignert, Helga Gunnlaugsdóttir, Nikolaus Gantner, Simon Wilson, Mary Gamberg, Øystein Wiig, Pat Roach, Robert J. Letcher, Frank Rigét, Gary A. Stern, Erik W. Born, Marlene S. Evans, Rune Dietz, and Birgit M. Braune
Subjects: Environmental Engineering, Arctic Regions, Sampling (statistics), Biota, Mercury, Circumpolar star, Pollution, Marine species, The arctic, Oceanography, Arctic, Environmental monitoring, Animals, Environmental Chemistry, Environmental science, Environmental Pollutants, Terrestrial ecosystem, Environmental Pollution, Waste Management and Disposal, geographic locations, Environmental Monitoring
Abstract: A statistically robust method was applied to 83 time-series of mercury in Arctic biota from marine, freshwater and terrestrial ecosystems with the purpose of generating a 'meta-analysis' of temporal trend data collected over the past two to three decades, mostly under the auspices of the Arctic Monitoring and Assessment Program (AMAP). Sampling locations ranged from Alaska in the west to northern Scandinavia in the east. Information from recently published temporal trend studies was tabulated to supplement the results of the statistical analyses. No generally consistent trend was evident across tissues and species from the circumpolar Arctic during the last 30years or so. However, there was a clear west-to-east gradient in the occurrence of recent increasing Hg trends, with larger numbers and a higher proportion of biotic datasets in the Canadian and Greenland region of the Arctic showing significant increases than in the North Atlantic Arctic. Most of the increasing datasets were for marine species, especially marine mammals. A total of 16 (19%) out of the 83 time-series could be classified as "adequate", where adequate is defined as the number of actual monitoring years in a time-series being equal to or greater than the number of years of sampling required to detect a 5% annual change in Hg concentrations, with a significance level of P
Published: 2011
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50. Regional Contamination versus Regional Dietary Differences: Understanding Geographic Variation in Brominated and Chlorinated Contaminant Levels in Polar Bears

Author: Robert J. Letcher, Thomas J. Evans, Rune Dietz, Elizabeth Peacock, Marsha Branigan, Christian Sonne, Erik W Born, Jon Aars, Derek C G Muir, Melissa A. McKinney, and Geir Wing Gabrielsen
Subjects: Canada, Ursus maritimus, Greenland, Bromine Compounds, Svalbard, biology.animal, Halogenated Diphenyl Ethers, Animals, Environmental Chemistry, Flame Retardants, biology, δ13C, Ecology, Stable isotope ratio, General Chemistry, δ15N, Contamination, Explained variation, Polychlorinated Biphenyls, Diet, Arctic, Environmental Pollutants, Female, Chlorine Compounds, Bay, Alaska, Ursidae, Environmental Monitoring
Abstract: The relative contribution of regional contamination versus dietary differences to geographic variation in polar bear (Ursus maritimus) contaminant levels is unknown. Dietary variation between Alaska, Canada, East Greenland, and Svalbard subpopulations was assessed by muscle nitrogen and carbon stable isotope (δ(15)N, δ(13)C) and adipose fatty acid (FA) signatures relative to their main prey (ringed seals). Western and southern Hudson Bay signatures were characterized by depleted δ(15)N and δ(13)C, lower proportions of C(20) and C(22) monounsaturated FAs and higher proportions of C(18) and longer chain polyunsaturated FAs. East Greenland and Svalbard signatures were reversed relative to Hudson Bay. Alaskan and Canadian Arctic signatures were intermediate. Between-subpopulation dietary differences predominated over interannual, seasonal, sex, or age variation. Among various brominated and chlorinated contaminants, diet signatures significantly explained variation in adipose levels of polybrominated diphenyl ether (PBDE) flame retardants (14-15%) and legacy PCBs (18-21%). However, dietary influence was contaminant class-specific, since only low or nonsignificant proportions of variation in organochlorine pesticide (e.g., chlordane) levels were explained by diet. Hudson Bay diet signatures were associated with lower PCB and PBDE levels, whereas East Greenland and Svalbard signatures were associated with higher levels. Understanding diet/food web factors is important to accurately interpret contaminant trends, particularly in a changing Arctic.
Published: 2010
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