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High ceftazidime-avibactam resistance among carbapenem-resistant Enterobacter species: Data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme, 2014–2021

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International Journal of Antimicrobial Agents 2024年第4期63卷 107105-107105页

作者： Wang, Jiun-Ling Lai, Chih-Cheng Tsai, Ya-Wen Ko, Wen-Chien Hsueh, Po-Ren Department of Medicine College of Medicine National Cheng Kung University Tainan Taiwan Department of Internal Medicine National Cheng Kung University Hospital Tainan Taiwan Division of Hospital Medicine Department of Internal Medicine Chi Mei Medical Center Tainan Taiwan School of Medicine College of Medicine National Sun Yat-sen University Kaohsiung Taiwan Center of Integrative Medicine Chi Mei Medical Center Tainan Taiwan Division of Infectious Diseases Department of Internal Medicine China Medical University Hospital School of Medicine China Medical University Taichung Taiwan Department of Laboratory Medicine China Medical University Hospital School of Medicine China Medical University Taichung Taiwan PhD Program for Ageing School of Medicine China Medical University Taichung Taiwan

Objectives: Trends in the susceptibility to ceftazidime-avibactam (CZA) and tigecycline (TGC) among Enterobacter species from different geographic areas are *** study aimed to analyse the trends in CZA and TGC susceptibility changes across different continents from 2014 to 2021 utilizing Antimicrobial Testing Leadership and Surveillance (ATLAS) data. Methods: A total of 23 669 isolates of Enterobacter species were collected over an 8-y period. Results: The overall non-susceptibility rate of Enterobacter isolates to both CZA and TGC was 3.2%. India (16.5%), Guatemala (15.4%), and the Philippines (13.1%) exhibited the highest resistance to CZA. The increase in CZA resistance rates was particularly evident in Asia, with an increase from 4.0% to 8.3%, and in Latin America, from 1.5% to 5%. The non-susceptibility rate for TGC mildly increased in Africa/Middle East but decreased in other continents during the study period. The overall rate of carbapenem resistance increased from 2.9% in 2014–2017 to 4.3% in 2018–2021. Among carbapenem-resistant Enterobacter isolates, the CZA resistance rate was highest in Asia (87.4%), followed by Europe (69.2%) and Africa/Middle East (60.8%). Among the 380 Enterobacter isolates resistant to CZA and carbapenem, the most common genotype of carbapenemase genes was bla_NDM (59.2%), followed by bla_VIM (24.2%), bla_OXA (4.2%), bla_IMP (1.1%), and bla_KPC (1.1%). The susceptibility of carbapenem-resistant Enterobacter to TGC remained high, with an overall susceptibility rate of 90%. Conclusions: The heterogeneous distribution of CZA resistance rates among different geographical regions highlights the divergent therapeutic options for drug-resistant Enterobacter species. © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy

关键词： Carbapenem resistance Ceftazidime-avibactam Enterobacter Tigecycline

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Global trends in nonsusceptibility rates of Escherichia coli isolates to meropenem and ceftazidime/avibactam: Data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme, 2014–21

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International Journal of Antimicrobial Agents 2024年第4期63卷 107103-107103页

作者： Wang, Jiun-Ling Lai, Chih-Cheng Tsai, Ya-Wen Hsueh, Chun-Chung Ko, Wen-Chien Hsueh, Po-Ren Department of Medicine College of Medicine National Cheng Kung University Tainan Taiwan Department of Internal Medicine National Cheng Kung University Hospital Tainan Taiwan Division of Hospital Medicine Department of Internal Medicine Chi Mei Medical Center Tainan Taiwan School of Medicine College of Medicine National Sun Yat-sen University Kaohsiung Taiwan Center of Integrative Medicine Chi Mei Medical Center Tainan Taiwan Department of Internal Medicine Taipei Veterans General Hospital Taipei Taiwan Division of Infectious Diseases Department of Internal Medicine China Medical University Hospital School of Medicine China Medical University Taichung Taiwan Department of Laboratory Medicine China Medical University Hospital School of Medicine China Medical University Taichung Taiwan PhD Program for Ageing School of Medicine China Medical University Taichung Taiwan

Objective: To understand the global changes in the nonsusceptibility rates of Escherichia coli to meropenem and ceftazidime-avibactam (CZA), we conducted a study using the Antimicrobial Testing Leadership and Surveillance database. Methods: A total of 49 394 E. coli isolates were collected during the 8-year study period. Result: The countries with the highest nonsusceptible rates for meropenem were India (16.6%), followed by Pakistan (6.7%), Ukraine (5.4%), Qatar (5.3%), and Guatemala (3.2%). For CZA, the nonsusceptible rate was highest in India (15.6%), followed by Qatar (4.0%), Guatemala (3.9%), China (2.6%), and Thailand (2.5%). During the study period, the nonsusceptible rates of meropenem and CZA in E. coli increased in Asia, Latin America, and Africa/Middle East. Isolates from the medical ICU (odds ratio [OR], 4.62) and surgical ICU (OR, 3.98) were associated with a higher risk of CZA nonsusceptible rates. Compared to intestinal specimens, respiratory and genitourinary specimens had the highest OR (2.32 and 2.17) associated with CZA resistance. Further analysis of carbapenemase distribution showed an increase in the percentage of bla_NDM-positive isolates and a decrease in bla_KPC-positive isolates worldwide, especially in Latin America. Additionally, we observed a gradual decline in the prevalence of bla_OXA-positive E. coli without concomitant carriage of metallo-β-lactamase genes in the worldwide surveillance. Conclusions: Further surveillance is necessary to determine whether bla_NDM -positive E. coli (i.e., CZA-resistant isolates) is increasing and leading to more superbugs spreading worldwide. © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy

关键词： ATLAS Ceftazidime-avibactam Escherichia coli Meropenem resistance New Delhi metallo-β-lactamase (blaNDM)

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Geographical patterns of in vitro susceptibilities to tigecycline and colistin among worldwide isolates of Acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniae: Data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme, 2016-2021

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INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS 2023年第3期62卷 106930-106930页

作者： Wang, Jiun-Ling Lai, Chih-Cheng Ko, Wen-Chien Hsueh, Po-Ren Natl Cheng Kung Univ Coll Med Dept Med Tainan Taiwan Natl Cheng Kung Univ Hosp Dept Internal Med Tainan Taiwan Div Hosp Med Dept Internal Med Chi Mei Med Ctr Tainan Taiwan Natl Sun Yat Sen Univ Coll Med Sch Med Kaohsiung Taiwan China Med Univ China Med Univ Hosp Dept Internal Med Div Infect DisSch Med Taichung Taiwan China Med Univ China Med Univ Hosp Sch Med Dept Lab Med Taichung Taiwan China Med Univ Sch Med PhD Program Ageing Taichung Taiwan China Med Univ China Med Univ Hosp Dept Lab Med 2 Yude Rd Taichung 40447 Taiwan China Med Univ China Med Univ Hosp Dept Internal Med 2 Yude Rd Taichung 40447 Taiwan Natl Cheng Kung Univ Hosp Dept Internal Med Tainan Taiwan

This study aimed to investigate the geographical trends of minimum inhibitory concentrations (MICs) for tigecycline and colistin in Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae isolates which were collected for the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme from 2016-2021. MICs of the isolates were determined using the broth microdilution method. In the study period, there was an increase in MIC50 and MIC90 values in Asia for tigecycline MICs in A. baumannii isolates, and the geometric mean of MICs increased significantly from 0.51-0.96 (R-2 value of 0.912). The isolates in Europe and Latin America also showed an increase in the geometric mean, but the percentage of MIC values <= 2 mg/L decreased from 99.7% to 86.7% in Asia. Among the Asian countries studied, China (90.9%), Thailand (94.3%), and Malaysia (95.5%) showed the lower percentages of tigecycline MIC values <0.5 mg/L for E. coli isolates. In terms of colistin susceptibility among A. baumannii isolates, there was no increase in MIC50/MIC90 or the geometric mean from 2016-2021. Compared to other continents, A. baumannii isolates in Europe had the highest MIC50 (0.5 mg/L), MI90 (2 mg/L), and geometric mean (0.55 mg/L). For E. coli, the percentage of colistin MIC values <= 2 mg/L was consistently > 98% in the study areas from 2016-2021. Among K. pneumoniae isolates, Europe and Latin America had higher geometric means of MICs (0.41 and 0.4 mg/L, respectively) and lower percentages of colistin MICs <= 2 mg/L than those in the other continents. (c) 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

关键词： Tigecycline Colistin Minimum inhibitory concentrations Acinetobacter baumannii Escherichia coli Klebsiella pneumoniae

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Unified classification and risk-stratification in Acute Myeloid Leukemia

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NATURE COMMUNICATIONS 2022年第1期13卷 4622页

作者： Tazi, Yanis Ossa, Juan Arango Zhou, Yangyu Bernard, Elsa Thomas, Ian Gilkes, Amanda Freeman, Sylvie Pradat, Yoann Johnson, Sean Hills, Robert Dillon, Richard Levine, Max Leongamornlert, Dan Butler, Adam Ganser, Arnold Bullinger, Lars Doehner, Konstanze Ottmann, Oliver Adams, Richard Doehner, Hartmut Campbell, Peter Burnett, Alan Dennis, Michael Russell, Nigel Devlin, Sean Huntly, Brian Papaemmanuil, Elli Mem Sloan Kettering Canc Ctr Dept Epidemiol & Biostat Computat Oncol Serv New York NY 10021 USA Mem Sloan Kettering Canc Ctr Ctr Hematol Malignancies 1275 York Ave New York NY 10021 USA Cornell Univ Weill Cornell Med Triinst Computat Biol & Med PhD Program New York NY 10021 USA Rockefeller Univ 1230 York Ave New York NY 10021 USA Cardiff Univ Ctr Trials Res Sch Med Cardiff Wales Cardiff Univ Sch Med Dept Haematol Cardiff Wales Univ Birmingham Inst Immunol & Immunotherapy Birmingham W Midlands England Univ Oxford Nuffield Dept Populat Hlth Oxford England Kings Coll London Dept Med & Mol Genet London England Wellcome Sanger Inst Canc Ageing & Somat Mutat Programme Hinxton England Hannover Med Sch Dept Hematol Hemostasis Oncol & Stem Cell Transpl Hannover Germany Campus Virchow Klinikum Dept Hematol Oncol & Tumorimmunol Berlin Germany Charite Univ Med Berlin Berlin Germany Free Univ Berlin Berlin Germany Humboldt Univ Berlin Germany Ulm Univ Dept Internal Med 3 Ulm Germany Univ Glasgow Glasgow Lanark Scotland Cardiff Univ Cardiff Wales Christie NHS Fdn Trust Manchester Lancs England Nottingham Univ Hosp Dept Haematol Nottingham England Univ Cambridge Dept Haematol Cambridge England Univ Cambridge Wellcome Trust MRC Cambridge Stem Cell Inst Cambridge England

Clinical recommendations for Acute Myeloid Leukemia (AML) classification and risk-stratification remain heavily reliant on cytogenetic findings at diagnosis, which are present in <50% of patients. Using comprehensive molecular profiling data from 3,653 patients we characterize and validate 16 molecular classes describing 100% of AML patients. Each class represents diverse biological AML subgroups, and is associated with distinct clinical presentation, likelihood of response to induction chemotherapy, risk of relapse and death over time. Secondary AML-2, emerges as the second largest class (24%), associates with high-risk disease, poor prognosis irrespective of flow Minimal Residual Disease (MRD) negativity, and derives significant benefit from transplantation. Guided by class membership we derive a 3-tier risk-stratification score that re-stratifies 26% of patients as compared to standard of care. This results in a unified framework for disease classification and risk-stratification in AML that relies on information from cytogenetics and 32 genes. Last, we develop an open-access patient-tailored clinical decision support tool. Classification and risk-stratification for Acute Myeloid Leukemia (AML) at diagnosis are primarily based on cytogenetics and only a few gene mutations. Here, the authors study the genomic landscape of 3653 AML patients and characterize 16 non-overlapping molecular subgroups of clinical relevance for disease classification and risk prognostication.

关键词： Cancer genomics Cancer genomics Acute myeloid leukaemia

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Physical activity and exercise for the prevention and management of mild cognitive impairment and dementia: a collaborative international guideline

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EUROPEAN GERIATRIC MEDICINE 2023年第5期14卷 925-952页

作者： Veronese, Nicola Soysal, Pinar Demurtas, Jacopo Solmi, Marco Bruyere, Olivier Christodoulou, Nikos Ramalho, Rodrigo Fusar-Poli, Paolo Lappas, Andreas S. Pinto, Daniel Frederiksen, Kristian Steen Corbi, Grazia Maria Karpenko, Olga Georges, Jean Duraes, Joao Schlogl, Mathias Yilmaz, Ozlem Sieber, Cornel Shenkin, Susan D. Smith, Lee Reginster, Jean-Yves Maggi, Stefania Limongi, Federica Ars, Joan Barbagallo, Mario Cherubini, Antonio Quinn, Terry Univ Palermo Dept Internal Med & Geriatr Geriatr Unit Via Vespro 141 I-90127 Palermo Italy Bezmialem Vakif Univ Dept Geriatr Med Fac Med Istanbul Turkiye Univ Modena & Reggio Emilia Clin & Expt Med PhD Program Modena Azienda USL Sud Est Toscana Grosseto Italy Univ Ottawa Dept Psychiat Ottawa ON Canada Ottawa Hosp Dept Mental Hlth Ottawa ON Canada Charite Dept Child & Adolescent Psychiat Berlin Germany Univ Liege Div Publ Hlth Epidemiol & Hlth Econ Collaborating Ctr Epidemiol Musculoskeletal Hlth WHO Liege Belgium Univ Thessaly Dept Psychiat Med Sch Volos Greece Univ Nottingham Sect Prevent Psychiat World Psychiat Assoc Med Sch Nottingham England Univ Auckland Sch Populat Hlth Dept Social & Community Hlth Auckland New Zealand Kings Coll London Dept Psychosis Studies London England Univ Pavia Dept Brain & Behav Sci Pavia Italy Univ Thessaly Dept Psychiat Fac Med Larisa Greece Aneurin Bevan Univ Hlth Board Newport Wales Marquette Univ Dept Phys Therapy Coll Hlth Sci Milwaukee WI USA Rigshosp Dept Neurol Danish Dementia Res Ctr Copenhagen Univ Hosp Copenhagen Denmark Univ Naples Federico II Dept Translat Med Sci Naples Italy Mental Hlth Clin 1 WPA Prevent Psychiat Sect Moscow Russia Alzheimer Europe Luxembourg Luxembourg Coimbra Univ Hosp Ctr Neurol Dept Coimbra Portugal Coimbra Univ Fac Med Coimbra Portugal Clin Barmelweid Div Geriatr Med Barmelweid Switzerland Istanbul Training & Res Hosp Dept Geriatr Med Istanbul Turkiye Friedrich Alexander Univ Erlangen Nurnberg Inst Biomed Aging Kobergerstr 60 D-90408 Nurnberg Germany Kantonsspital Winterthur Dept Med Brauerstr 15Postfach 834 CH-8401 Winterthur Switzerland Univ Edinburgh Usher Inst Ageing & Hlth Res Grp Edinburgh Scotland Univ Edinburgh Usher Inst Adv Care Res Ctr Edinburgh Scotland Anglia Ruskin Univ Ctr Hlth Performance & Wellbeing Cambridge England Univ Liege Div Publ Hlth Epidemiol & Hlth Econ Liege Belgium CNR Aging Branch Neurosci Inst Padua Italy

Background Physical activity and exercise have been suggested as effective interventions for the prevention and management of mild cognitive impairment (MCI) and dementia, but there are no international *** To create a set of evidence- and expert consensus-based prevention and management recommendations regarding physical activity (any bodily movement produced by skeletal muscles that results in energy expenditure) and exercise (a subset of physical activity that is planned, structured, repetitive), applicable to a range of individuals from healthy older adults to those with MCI/*** Guideline content was developed with input from several scientific and lay representatives' societies. A systematic search across multidisciplinary databases was carried out until October 2021. Recommendations for prevention and management were developed according to the GRADE and complemented by consensus statements from the expert *** Physical activity may be considered for the primary prevention of dementia. In people with MCI there is continued uncertainty about the role of physical activity in slowing the conversion to dementia. Mind-body interventions have the greatest supporting evidence. In people with moderate dementia, exercise may be used for maintaining disability and cognition. All these recommendations were based on a very low/low certainty of *** Although the scientific evidence on the beneficial role of physical activity and exercise in preserving cognitive functions in subjects with normal cognition, MCI or dementia is inconclusive, this panel, composed of scientific societies and other stakeholders, recommends their implementation based on their beneficial effects on almost all facets of health.

关键词： Cognition Dementia Mild cognitive impairment Guidelines Physical activity Exercise Older adult

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Sex Differences in Clustering Unhealthy Lifestyles Among Survivors of COVID-19: Latent Class Analysis

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JMIR PUBLIC HEALTH AND SURVEILLANCE 2024年 10卷 e50189页

作者： Le, Lan T. H. Hoang, Thi Ngoc Anh Nguyen, Tan Dao, Tien Do, Binh N. Pham, Khue M. Vu, Vinh H. Pham, Linh, V Nguyen, Lien T. H. Nguyen, Hoang C. Tran, Tuan, V Nguyen, Trung H. Nguyen, Anh Nguyen, Hoan, V Nguyen, Phuoc B. Nguyen, Hoai T. T. Pham, Thu T. M. Le, Thuy Nguyen, Thao T. P. Tran, Cuong Q. Quach, Ha-Linh Nguyen, Kien Van Duong, Tuyen Thai Nguyen Natl Hosp Thai Nguyen Vietnam Thai Nguyen Natl Hosp Training & Direct Healthcare Act Ctr Thai Nguyen Vietnam Thai Nguyen Natl Hosp Biochem Dept Thai Nguyen Vietnam Phenikaa Univ Fac Med Hanoi Vietnam Can Tho Univ Med & Pharm Dept Orthoped Can Tho Vietnam Can Tho Univ Med & Pharm Hosp Can Tho Vietnam Mil Hosp 175 Inst Oncol & Nucl Med Ho Chi Minh City Vietnam Vietnam Mil Med Univ Dept Infect Dis Hanoi Vietnam Vietnam Mil Med Univ Dept Mil Sci Hanoi Vietnam Hai Phong Univ Med & Pharm Fac Publ Hlth Hai Phong Vietnam Viet Tiep Hosp Infect & Trop Dis Dept Hai Phong Vietnam Hai Phong Univ Med & Pharm Hosp Dept Pulm & Cardiovasc Dis Hai Phong Vietnam Thai Nguyen Univ Med & Pharm Thai Nguyen Vietnam Thai Nguyen Univ Med & Pharm Neurol Dept Thai Nguyen Vietnam Gang Thep Hosp Thai Nguyen Vietnam Hosp Trop Dis Hai Duong Vietnam Hai Phong Univ Med & Pharm Dept Infect Dis Hai Phong Vietnam Kien An Hosp Hai Phong Vietnam Kien An Hosp Training & Direct Healthcare Act Ctr Hai Phong Vietnam Taipei Med Univ Coll Publ Hlth Sch Publ Hlth Taipei Taiwan Da Nang Univ Med Technol & Pharm Da Nang Vietnam Da Nang Univ Med Technol & Pharm Fac Med Lab Sci Da Nang Vietnam Hue Univ Univ Med & Pharm Inst Community Hlth Res Hue Vietnam Pham Ngoc Thach Univ Med Fac Publ Hlth Ho Chi Minh City Vietnam Natl Univ Singapore Duke NUS Med Sch Ctr Ageing Res & Educ Singapore Singapore Hanoi Univ Publ Hlth Fac Social & Behav Sci Dept Hlth Promot Hanoi Vietnam Taipei Med Univ Sch Nutr & Hlth Sci Taipei Taiwan Taipei Med Univ Int Master PhD Program Med Taipei Taiwan

Background: The COVID-19 pandemic has underscored the significance of adopting healthy lifestyles to mitigate the risk of severe outcomes and long-term consequences. Objective: This study focuses on assessing the prevalence and clustering of 5 unhealthy lifestyle behaviors among Vietnamese adults after recovering from COVID-19, with a specific emphasis on sex differences. Methods: The cross-sectional data of 5890 survivors of COVID-19 in Vietnam were analyzed from December 2021 to October 2022. To examine the sex differences in 5 unhealthy lifestyle behaviors (smoking, drinking, unhealthy diet, physical inactivity, and sedentary behavior), the percentages were plotted along with their corresponding 95% CI for each behavior. Latent class analysis was used to identify 2 distinct classes of individuals based on the clustering of these behaviors: the "less unhealthy" group and the "more unhealthy" group. We examined the sociodemographic characteristics associated with each identified class and used logistic regression to investigate the factors related to the "more unhealthy" group. Results: The majority of individuals (male participants: 2432/2447, 99.4% and female participants: 3411/3443, 99.1%) exhibited at least 1 unhealthy behavior, with male participants being more susceptible to multiple unhealthy behaviors. The male -to -female ratio for having a single behavior was 1.003, but it escalated to 25 for individuals displaying all 5 behaviors. Male participants demonstrated a higher prevalence of combining alcohol intake with sedentary behavior (949/2447, 38.8%) or an unhealthy diet (861/2447, 35.2%), whereas female participants tended to exhibit physical inactivity combined with sedentary behavior (1305/3443, 37.9%) or an unhealthy diet (1260/3443, 36.6%). Married male participants had increased odds of falling into the "more unhealthy" group compared to their single counterparts (odds ratio [OR] 1.45, 95% CI 1.14-1.85), while female participants exhibited lower odd

关键词： sex difference cluster lifestyle behavior COVID-19 recovery latent class analysis sex unhealthy lifestyle adult long COVID-19 infected survivor public health intervention promote well-being COVID-19 adults mobile phone

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Differential levels of IFNα subtypes in autoimmunity and viral infection

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CYTOKINE 2021年 144卷 155533-155533页

作者： Bondet, Vincent Rodero, Mathieu P. Posseme, Celine Bost, Pierre Decalf, Jeremie Haljasmagi, Liis Bekaddour, Nassima Rice, Gillian, I Upasani, Vinit Herbeuval, Jean-Philippe Reynolds, John A. Briggs, Tracy A. Bruce, Ian N. Mauri, Claudia Isenberg, David Menon, Madhvi Hunt, David Schwikowski, Benno Mariette, Xavier Pol, Stanislas Rozenberg, Flore Cantaert, Tineke Gottenberg, J. Eric Kisand, Kai Duffy, Darragh Inst Pasteur Translat Immunol Lab 25 Rue Dr Roux F-75724 Paris 15 France Univ Paris UMR8601 CNRS Chim & Biol Modelisat & Immunol Therapie CBMIT Paris France Univ Paris CRI Doctoral Sch Frontiers Innovat Res & Educ PhD Program F-75005 Paris France Inst Pasteur Dept Computat Biol Syst Biol Grp F-75015 Paris France Inst Pasteur USR 3756 F-75015 Paris France CNRS F-75015 Paris France Sorbonne Univ Complexite Vivant F-75005 Paris France Univ Tartu Inst Biomed & Translat Med Mol Pathol Tartu Estonia Univ Manchester Ctr Musculoskeletal Res Sch Biol Sci Div Musculoskeletal & Dermatol Sci Manchester Lancs England Inst Pasteur Int Network Inst Pasteur Cambodge Immunol Unit Phnom Penh Cambodia Univ Manchester Manchester Univ NHS Fdn Trust Manchester Acad Hlth Sci Ctr NIHR Manchester Biomed Res Ctr Manchester Lancs England Univ Birmingham Coll Med & Dent Sci Inst Inflammat & Ageing Rheumatol Res Grp Birmingham W Midlands England Sandwell & West Birmingham NHS Trust Rheumatol Dept Birmingham W Midlands England Univ Manchester Sch Biol Sci Div Evolut & Genom Sci Manchester Lancs England Manchester Univ Hosp NHS Fdn Trust Manchester Ctr Genom Med St Marys Hosp Manchester Lancs England UCL Ctr Rheumatol Res Div Med London WC1E 6JF England Univ Edinburgh Ctr Genom & Expt Med Med Res Council Inst Genet & Mol Med Edinburgh Midlothian Scotland Univ Paris Saclay INSERM UMR1184 Hop Bicetre Assistance Publ Hop Paris AP HP Le Kremlin Bicetre France Hop Cochin Assistance Publ Hop Paris AP HP Unite Hepatol Paris France Univ Paris Dept Virol APHP CUP Paris France Univ Strasbourg Fac Med Strasbourg France Univ Manchester Sch Biol Sci Lydia Becker Inst Immunol & Inflammat Div Infect Immun & Resp Med Manchester Lancs England

Type I interferon are essential for host response to viral infections, while dysregulation of their response can result in autoinflammation or autoimmunity. Among IFN alpha (alpha) responses, 13 subtypes exist that signal through the same receptor, but have been reported to have different effector functions. However, the lack of available tools for discriminating these closely related subtypes, in particular at the protein level, has restricted the study of their differential roles in disease. We developed a digital ELISA with specificity and high sensitivity for the IFN alpha 2 subtype. Application of this assay, in parallel with our previously described pan-IFNa assay, allowed us to study different IFN alpha protein responses following cellular stimulation and in diverse patient cohorts. We observed different ratios of IFN alpha protein responses between viral infection and autoimmune patients. This analysis also revealed a small percentage of autoimmune patients with high IFN alpha 2 protein measurements but low pan-IFN alpha measurements. Correlation with an ISG score and functional activity showed that in this small sub group of patients, IFN alpha 2 protein measurements did not reflect its biological activity. This unusual phenotype was partly explained by the presence of anti-IFN alpha auto-antibodies in a subset of autoimmune patients. This study reports ultrasensitive assays for the study of IFN alpha proteins in patient samples and highlights the insights that can be obtained from the use of multiple phenotypic readouts in translational and clinical studies.

关键词： IFN alpha subtypes TLR activation IFN function Anti-IFN alpha autoantibodies Viral infection Autoimmunity

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Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

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NATURE GENETICS 2020年第3期52卷 306-+页

作者： Rodriguez-Martin, Bernardo Alvarez, Eva G. Baez-Ortega, Adrian Zamora, Jorge Supek, Fran Demeulemeester, Jonas Santamarina, Martin Ju, Young Seok Temes, Javier Garcia-Souto, Daniel Detering, Harald Li, Yilong Rodriguez-Castro, Jorge Dueso-Barroso, Ana Bruzos, Alicia L. Dentro, Stefan C. Blanco, Miguel G. Contino, Gianmarco Ardeljan, Daniel Tojo, Marta Roberts, Nicola D. Zumalave, Sonia Edwards, Paul A. W. Weischenfeldt, Joachim Puiggros, Montserrat Chong, Zechen Chen, Ken Lee, Eunjung Alice Wala, Jeremiah A. Raine, Keiran Butler, Adam Waszak, Sebastian M. Navarro, Fabio C. P. Schumacher, Steven E. Monlong, Jean Maura, Francesco Bolli, Niccolo Bourque, Guillaume Gerstein, Mark Park, Peter J. Wedge, David C. Beroukhim, Rameen Torrents, David Korbel, Jan O. Martincorena, Inigo Fitzgerald, Rebecca C. Van Loo, Peter Kazazian, Haig H. Burns, Kathleen H. Campbell, Peter J. Tubio, Jose M. C. Akdemir, Kadir C. Boutros, Paul C. Bowtell, David D. L. Brors, Benedikt Chan, Kin Cortes-Ciriano, Isidro Dunford, Andrew J. Edwards, Paul A. Estivill, Xavier Etemadmoghadam, Dariush Feuerbach, Lars Fink, J. Lynn Frenkel-Morgenstern, Milana Garsed, Dale W. Gordenin, Dmitry A. Haan, David Haber, James E. Hess, Julian M. Hutter, Barbara Imielinski, Marcin Jones, David T. W. Kazanov, Marat D. Klimczak, Leszek J. Koh, Youngil Kumar, Kiran Lee, Jake June-Koo Lynch, Andy G. Macintyre, Geoff Markowetz, Florian Martinez-Fundichely, Alexander Meyerson, Matthew Miyano, Satoru Nakagawa, Hidewaki Ossowski, Stephan Pearson, John, V Rippe, Karsten Roberts, Steven A. Scully, Ralph Shackleton, Mark Sidiropoulos, Nikos Sieverling, Lina Stewart, Chip Villasante, Izar Waddell, Nicola Yang, Lixing Yao, Xiaotong Yoon, Sung-Soo Zhang, Cheng-Zhong Univ Santiago de Compostela Ctr Res Mol Med & Chron Dis CIMUS Genomes & Dis Santiago De Compostela Spain Univ Santiago de Compostela Dept Zool Genet & Phys Anthropol Santiago De Compostela Spain Univ Vigo Biomed Res Ctr CINBIO Vigo Spain Univ Cambridge Dept Vet Med Transmissible Canc Grp Cambridge England Barcelona Inst Sci & Technol Inst Res Biomed IRB Barcelona Genome Data Sci Barcelona Spain ICREA Barcelona Spain Francis Crick Inst London England Univ Leuven Dept Human Genet Leuven Belgium Korea Adv Inst Sci & Technol Grad Sch Med Sci & Engn Daejeon South Korea Wellcome Sanger Inst Canc Ageing & Somat Mutat Programme Cambridge England Univ Vigo Dept Biochem Genet & Immunol Vigo Spain Galicia Hlth Res Inst Vigo Spain CNS BSC Barcelona Spain Univ Vic Fac Sci & Technol Cent Univ Catalonia UVic UCC Vic Spain Wellcome Sanger Inst Expt Canc Genet Cambridge England Univ Oxford Oxford Big Data Inst Oxford England Univ Santiago de Compostela Ctr Res Mol Med & Chron Dis CIMUS DNA Repair & Genome Integr Santiago De Compostela Spain Univ Santiago de Compostela Dept Biochem & Mol Biol Santiago De Compostela Spain Univ Cambridge MRC Canc Unit Cambridge England Johns Hopkins Univ Dept Genet Med Sch Med Baltimore MD USA Univ Cambridge Dept Pathol Cambridge England Univ Cambridge Canc Res UK Cambridge Inst Cambridge England Univ Copenhagen Biotech Res & Innovat Ctr Copenhagen Denmark Rigshosp Finsen Lab Copenhagen Denmark European Mol Biol Lab Genome Biol Unit Heidelberg Germany Univ Texas MD Anderson Canc Ctr Dept Bioinformat & Computat Biol Houston TX 77030 USA Univ Alabama Birmingham Sch Med Dept Genet Birmingham AL USA Univ Alabama Birmingham Sch Med Informat Inst Birmingham AL USA Harvard Med Sch Boston Childrens Hosp Div Genet & Genom Boston MA 02115 USA Broad Inst Harvard & MIT Cambridge MA USA Dana Farber Canc Inst Dept Canc Biol Boston MA 02115 USA Dana Farber Canc Inst Dept Med Oncol Boston MA 02115 USA Yale Univ Pr

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1;L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage-fusion-bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors. An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

关键词： Cancer Genomics

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Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults

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JOURNAL OF AFFECTIVE DISORDERS 2023年 326卷 249-261页

作者： Solmi, Marco Thompson, Trevor Estrade, Andres Agorastos, Agorastos Radua, Joaquim Cortese, Samuele Dragioti, Elena Leisch, Friedrich Vancampfort, Davy Thygesen, Lau Caspar Aschauer, Harald Schloegelhofer, Monika Aschauer, Elena Schneeberger, Andres Huber, Christian G. Hasler, Gregor Conus, Philippe Do Cuenod, Kim Q. von Kaenel, Roland Arrondo, Gonzalo Fusar-Poli, Paolo Gorwood, Philip Llorca, Pierre-Michel Krebs, Marie-Odile Scanferla, Elisabetta Kishimoto, Taishiro Rabbani, Golam Skonieczna-Zydecka, Karolina Brambilla, Paolo Favaro, Angela Takamiya, Akihiro Zoccante, Leonardo Colizzi, Marco Bourgin, Julie Kaminski, Karol Moghadasin, Maryam Seedat, Soraya Matthews, Evan Wells, John Vassilopoulou, Emilia Gadelha, Ary Su, Kuan-Pin Kwon, Jun Soo Kim, Minah Lee, Tae Young Papsuev, Oleg Mankova, Denisa Boscutti, Andrea Gerunda, Cristiano Saccon, Diego Righi, Elena Monaco, Francesco Croatto, Giovanni Cereda, Guido Demurtas, Jacopo Brondino, Natascia Veronese, Nicola Enrico, Paolo Politi, Pierluigi Ciappolino, Valentina Pfennig, Andrea Bechdolf, Andreas Meyer-Lindenberg, Andreas Kahl, Kai G. Domschke, Katharina Bauer, Michael Koutsouleris, Nikolaos Winter, Sibylle Borgwardt, Stefan Bitter, Istvan Balazs, Judit Czobor, Pal Unoka, Zsolt Mavridis, Dimitris Tsamakis, Konstantinos Bozikas, Vasilios P. Tunvirachaisakul, Chavit Maes, Michael Rungnirundorn, Teerayuth Supasitthumrong, Thitiporn Haque, Ariful Brunoni, Andre R. Costardi, Carlos Gustavo Schuch, Felipe Barreto Polanczyk, Guilherme Luiz, Jhoanne Merlyn Fonseca, Lais Aparicio, Luana V. Valvassori, Samira S. Nordentoft, Merete Vendsborg, Per Hoffmann, Sofie Have Sehli, Jihed Sartorius, Norman Heuss, Sabina Guinart, Daniel Hamilton, Jane Kane, John Rubio, Jose Sand, Michael Koyanagi, Ai Solanes, Aleix Andreu-Bernabeu, Alvaro Jose Caceres, Antonia San Arango, Celso Diaz-Caneja, Covadonga M. Hidalgo-Mazzei, Diego Vieta, Eduard Gonzalez-Penas, Javier Fortea, Lydia Parellada, Mara Fullana, Miquel A. Verdolini, Norma Andrlikova, Eva Janku, Karolina Millan, Mark John Honciuc, Univ Ottawa Dept Psychiat Ottawa ON Canada Ottawa Hosp Dept Mental Hlth Ottawa ON Canada Ottawa Hosp Res Inst OHRI Clin Epidemiol Program Ottawa ON Canada Kings Coll London Inst Psychiat Psychol & Neurosci Dept Psychosis Studies Early Psychosis Intervent & Clin Detect EPIC Lab London England Univ Southampton Sch Psychol Ctr Innovat Mental Hlth Dev Lab Southampton Hants England NHS Trust Southampton Hants England Charite Univ Med Berlin Dept Child & Adolescent Psychiat Berlin Germany Univ Greenwich Ctr Chron Illness & Ageing London England Univ Catolica Dept Psychol Montevideo Uruguay Aristotle Univ Thessaloniki Med Sch Div Neurosci Fac Hlth SciDept Psychiat 2 Thessaloniki Greece Univ Barcelona Inst Invest Biomed August Pi i Sunyer IDIBAPS Inst Salud Carlos III CIBERSAMImaging Mood & Anxiety Related Disorders Barcelona Spain Karolinska Inst Dept Clin Neurosci Ctr Psychiat Res & Educ Stockholm Sweden Univ Southampton Ctr Innovat Mental Hlth Southampton Hants England Linkoping Univ Pain & Rehabil Ctr Linkoping Sweden Linkoping Univ Dept Hlth Med & Caring Sci Linkoping Sweden Univ Ioannina Sch Hlth Sci Dept Nursing Res Lab Psychol Patients Families & Hlth Profess Ioannina Greece Univ Nat Resources & Life Sci Vienna Austria Katholieke Univ Leuven KU Leuven Dept Rehabil Sci Leuven Belgium Univ Southern Denmark Natl Inst Publ Hlth Odense Denmark Nonprofit Assoc Res Funding Ltd BioPsyC Biopsychosocial Corp Vienna Austria Univ Calif San Diego La Jolla CA 92093 USA Univ Basel Univ Psychiat Kliniken Basel UPK Basel Switzerland Univ Fribourg Fribourg Network Mental Hlth RFSM Fribourg Switzerland Univ Lausanne Dept Psychiat Lausanne Switzerland Univ Zurich Univ Hosp Zurich Dept Consultat Liaison Psychiat & Psychosomat Med Zurich Switzerland Univ Navarra Inst Culture & Soc ICS Mind Brain Grp Pamplona Spain South London & Maudsley NHS Fdn Trust OASIS Serv London England Univ Pavia Dept Brain & Behav Sci Pavia Italy Univ Paris Ci

Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT;***) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the in-ternal validity of the co-primary outcome, a composite psychopathology "P-score". Methods: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r >= 0.5 with validated companion question-naires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. Results: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (omega = 0.95). Factor structure was consistent across age and sex. Conclusions: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.

关键词： Covid-19 Pandemic COH-FIT

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Patterns of somatic structural variation in human cancer genomes (vol 578, pg 112, 2020)

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NATURE 2023年第7948期614卷 E38-E38页

作者： Li, Yilong Roberts, Nicola D. Wala, Jeremiah A. Shapira, Ofer Schumacher, Steven E. Kumar, Kiran Khurana, Ekta Waszak, Sebastian Korbel, Jan O. Haber, James E. Imielinski, Marcin Weischenfeldt, Joachim Beroukhim, Rameen Campbell, Peter J. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK Totient Inc Cambridge MA USA Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Department of Haematology University of Cambridge Cambridge UK Cambridge University Hospitals NHS Foundation Trust Cambridge UK Korea Advanced Institute of Science and Technology Daejeon South Korea Department of Zoology Genetics and Physical Anthropology University of Santiago de Compostela Santiago de Compostela Spain Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS) University of Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) University of Vigo Vigo Spain Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain Department of Zoology Genetics and Physical Anthropology (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) Universidade de Vigo Vigo Spain The Broad Institute of Harvard and MIT Cambridge MA USA Bioinformatics and Integrative Genomics Harvard University Cambridge MA USA Department of Cancer Biology Dana-Farber Cancer Institute Boston MA USA Broad Institute of MIT and Harvard Cambridge MA USA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA Harvard Medical School Boston MA USA Massachusetts General Hospital Center for Cancer Research Charlestown MA USA Dana-Farber Cancer Institute Boston MA USA Department of Biostatistics and Computational Biology Dana-Farber Cancer Institute and Harvard Medical School Boston MA USA Weill Cornell Medical College New York NY USA Department of Physiology and Biophysics Weill Cornell Medicine New York NY USA Institute for Computational Biomedicine Weill Cornell Medicine New York NY USA Controlled Department and Institution New York NY USA Englander Institute for Precision Medicine Weill Cornell Medicine Ne

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