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2. Immunological evaluation of young unvaccinated patients with Turner syndrome after COVID-19

Author

Mateus V. de Castro, Monize V.R. Silva, Luana de M. Oliveira, Sarah C. Gozzi-Silva, Michel S. Naslavsky, Marilia O. Scliar, Monize L. Magalhães, Katia M. da Rocha, Kelly Nunes, Erick C. Castelli, Jhosiene Y. Magawa, Keity S. Santos, Edecio Cunha-Neto, Maria N. Sato, and Mayana Zatz

Subjects
Microbiology (medical), Infectious Diseases, General Medicine
Published
2023
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4. Midterm Outcomes of Endovascular Repair of Aortic Arch Aneurysms with the Gore Thoracic Branch Endoprosthesis

Author

Nathan L. Liang, Michael D. Dake, Michael P. Fischbein, Joseph E. Bavaria, Nimesh D. Desai, Gustavo S. Oderich, Michael J. Singh, Mark Fillinger, Bjoern D. Suckow, Jon S. Matsumura, Himanshu J. Patel, and Michel S. Makaroun

Subjects
Surgery, Cardiology and Cardiovascular Medicine
Abstract

Aortic aneurysms involving aortic arch vessels are anatomically unsuitable for standard thoracic endovascular repair (TEVAR) without cervical debranching of the arch vessels. Three year outcomes of a single branched thoracic endograft following previous publication of peri-operative and one year outcomes are reported.This was a multicentre feasibility trial of the GORE TAG Thoracic Branch Endoprosthesis (TBE), a thoracic endovascular graft incorporating a single retrograde branch for aortic arch vessel perfusion. The first study arm enrolled patients with an intact descending thoracic aortic aneurysm extending to the distal arch with left subclavian artery (LSA) incorporation (zone 2). The second arm enrolled patients with arch aneurysms requiring incorporation of the left carotid or innominate artery (zone 0/1) and extra-anatomic surgical revascularisation of the remaining aortic arch vessels. Outcomes at three years are reported.The cohort comprised 40 patients (31 zone 2, nine zone 0/1). The majority were male (52%). Mean follow up was 1 408 ± 552 days in the zone 2 and 1 187 ± 766 days in the zone 0/1 cohort. During three year follow up there was no device migration, fracture, or aortic rupture in either arm. In the zone 2 arm, freedom from re-intervention was 97% at one and three years but there were two side branch occlusions. Two patients had aneurysm enlargement5 mm without documented endoleak or re-intervention. Freedom from death at one and three years was 90% and 84%. In the zone 0/1 arm there were no re-interventions, loss of branch patency, or aneurysm enlargement at three years. Cerebrovascular events occurred in three patients during follow up: two unrelated to the device or procedure, and one of unknown relationship. Two patients in this arm died during the follow up period, both unrelated to the procedure or the aneurysm.Initial three year results of the TBE device for endovascular repair of arch aneurysms show favourable patency and durability with low rates of graft related complications.

Published
2022
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5. Characterization of pharmacogenomic variants in a Brazilian admixed cohort of elderly individuals based on whole-genome sequencing data

Author

Luciana Bertholim-Nasciben, Marilia O. Scliar, Guilherme Debortoli, Bhooma Thiruvahindrapuram, Stephen W. Scherer, Yeda A. O. Duarte, Mayana Zatz, Guilherme Suarez-Kurtz, Esteban J. Parra, and Michel S. Naslavsky

Subjects
Pharmacology, Pharmacology (medical)
Abstract

Introduction: Research in the field of pharmacogenomics (PGx) aims to identify genetic variants that modulate response to drugs, through alterations in their pharmacokinetics (PK) or pharmacodynamics (PD). The distribution of PGx variants differs considerably among populations, and whole-genome sequencing (WGS) plays a major role as a comprehensive approach to detect both common and rare variants. This study evaluated the frequency of PGx markers in the context of the Brazilian population, using data from a population-based admixed cohort from Sao Paulo, Brazil, which includes variants from WGS of 1,171 unrelated, elderly individuals.Methods: The Stargazer tool was used to call star alleles and structural variants (SVs) from 38 pharmacogenes. Clinically relevant variants were investigated, and the predicted drug response phenotype was analyzed in combination with the medication record to assess individuals potentially at high-risk of gene-drug interaction.Results: In total, 352 unique star alleles or haplotypes were observed, of which 255 and 199 had a frequency < 0.05 and < 0.01, respectively. For star alleles with frequency > 5% (n = 97), decreased, loss-of-function and unknown function accounted for 13.4%, 8.2% and 27.8% of alleles or haplotypes, respectively. Structural variants (SVs) were identified in 35 genes for at least one individual, and occurred with frequencies >5% for CYP2D6, CYP2A6, GSTM1, and UGT2B17. Overall 98.0% of the individuals carried at least one high risk genotype-predicted phenotype in pharmacogenes with PharmGKB level of evidence 1A for drug interaction. The Electronic Health Record (EHR) Priority Result Notation and the cohort medication registry were combined to assess high-risk gene-drug interactions. In general, 42.0% of the cohort used at least one PharmGKB evidence level 1A drug, and 18.9% of individuals who used PharmGKB evidence level 1A drugs had a genotype-predicted phenotype of high-risk gene-drug interaction.Conclusion: This study described the applicability of next-generation sequencing (NGS) techniques for translating PGx variants into clinically relevant phenotypes on a large scale in the Brazilian population and explores the feasibility of systematic adoption of PGx testing in Brazil.

Published
2023
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6. A.G. PAPANDREOU’S ACADEMIC ECONOMIC THOUGHT 1943-1963

Author

Michel S. Zouboulakis

Abstract

The aim of this article is to make an overall assessment of Andreas Georges Papandreou’s theoretical contributions during his American academic career, from the perspective of the history of economic thought. Papandreou contributed to the post-war development of economic thought in competition theory and experimental testing of consumer theory. In developing competition theory, he introduced a new method of evaluating the monopolistic power of a firm through a coefficient measuring the firm’s penetration in the market. Furthermore, he suggested a way of experimentally testing whether individual preferences satisfy the axiom of transitivity. Lastly, he actively participated in the methodological controversies on the realisticness of economic assumptions which took place between 1946 and 1953, and on the empirical meaning of economics in 1963, between Friedman, Samuelson, Machlup, Simon and others.

Published
2023
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7. Optimal HLA imputation of admixed population with dimension reduction

Author

Venceslas Douillard, Nayane dos Santos Brito Silva, Sonia Bourguiba-Hachemi, Michel S. Naslavsky, Marilia O. Scliar, Yeda A. O. Duarte, Mayana Zatz, Maria Rita Passos-Bueno, Sophie Limou, Pierre-Antoine Gourraud, Élise Launay, Erick C. Castelli, and Nicolas Vince

Abstract

Human genomics has quickly evolved, powering genome-wide association studies (GWASs). SNP-based GWASs cannot capture the intense polymorphism ofHLAgenes, highly associated with disease susceptibility. There are methods to statistically imputeHLAgenotypes from SNP-genotypes data, but lack of diversity in reference panels hinders their performance. We evaluated the accuracy of the 1,000 Genomes data as a reference panel for imputing HLA from admixed individuals of African and European ancestries, focusing on (a) the full dataset, (b) 10 replications from 6 populations, (c) 19 conditions for the custom reference panels. The full dataset outperformed smaller models, with a good F1-score of 0.66 forHLA-B. However, custom models outperformed the multiethnic or population models of similar size (F1-scores up to 0.53, against up to 0.42). We demonstrated the importance of using genetically specific models for imputing admixed populations, which are currently underrepresented in public datasets, opening the door to HLA imputation for every genetic population.

Published
2023
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8. Supplementary Figure 2 from Recombinant Human Erythropoietin in Combination with Chemotherapy Increases Breast Cancer Metastasis in Preclinical Mouse Models

Author

Anargyros Xenocostas, Alison L. Allan, Alexandra Boasie, Michel S. Beausoleil, D. George Ormond, Jenny E. Chu, and Benjamin D. Hedley

Abstract

PDF file - 1147KB, 2 x 106 MDA-MB-231 or MDA-MB-435 cells were injected into 6- to 7-week-old female NOD/SCID or nu/nu mice via mammary fat pad. The control cohort (n=4) received weekly saline subcutaneous injections, while three other cohorts (n=4 per group) received rHuEPO doses of 300U/kg, 600U/kg or 1200U/kg. (A-D) Data from MDA-MB-231 breast cancer cells in NOD/SCID mice. (E-H) Results from MDA-MB-435 breast cancer cells injected into nude (nu/nu) mice. (A,E) Primary tumor growth of human breast cancer cells injected into mice over time. EPO treatment was initiated at 3 weeks post injection (black arrow). Data are presented as mean � SEM. (B,F) Incidence of lung metastasis (% of mice in each treatment group that developed metastases). (C,G) Size (diameter) of lung metastases scored. Data are presented as mean � SEM. (D,H) Number of lung metastases observed. Data are presented as the mean � SEM. For all panels, # denotes a statistically significant difference relative to the untreated control cohort (p

Published
2023
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9. Supplementary Tables 1-4 from Recombinant Human Erythropoietin in Combination with Chemotherapy Increases Breast Cancer Metastasis in Preclinical Mouse Models

Author

Anargyros Xenocostas, Alison L. Allan, Alexandra Boasie, Michel S. Beausoleil, D. George Ormond, Jenny E. Chu, and Benjamin D. Hedley

Abstract

PDF file - 119KB, Supplemental Table 1- Cell lines used. Supplemental Table 2 - PCR primers and cycling conditions. Supplemental Table 3 - Anti Human EPOR antibodies used. Supplemental Table 4 - In Vivo hemoglobin measurements.

Published
2023
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10. Data from Recombinant Human Erythropoietin in Combination with Chemotherapy Increases Breast Cancer Metastasis in Preclinical Mouse Models

Author

Anargyros Xenocostas, Alison L. Allan, Alexandra Boasie, Michel S. Beausoleil, D. George Ormond, Jenny E. Chu, and Benjamin D. Hedley

Abstract

Purpose: Erythropoiesis-stimulating agents (ESA) are used clinically for treating cancer-related anemia. Recent clinical trials have reported increased adverse events and reduced survival in ESA-treated breast cancer patients receiving chemotherapy, potentially related to erythropoietin (EPO)-induced cancer progression. However, minimal preclinical data are available about the impact of EPO on metastatic cell behavior and/or the metastatic process, and this was the goal of our study.Experimental Design: Breast cancer cell lines were treated with recombinant human EPO (rHuEPO) and screened for expression of EPO receptors (EPOR). MDA-MB-231 and MDA-MB-435 cell lines were used for functional assays in vitro (two-dimensional/three-dimensional growth and survival) and in vivo (tumorigenicity and metastasis), in the presence or absence of EPO and/or cytotoxic agents.Results: A large variation in EPOR expression across cell lines was observed. In vitro, rHuEPO had a protective effect on radiation-treated MDA-MB-435 cells (P < 0.05); however, rHuEPO treatment alone or combined with chemotherapy or hypoxia did not influence cell survival. In vivo, rHuEPO increased lung metastases in immunocompromised mice injected with MDA-MB-231 or MDA-MB-435 cells and treated with chemotherapy relative to mice treated with chemotherapy alone (P < 0.05).Conclusions: The lack of an in vitro effect of rHuEPO highlights the importance of in vivo studies to delineate the effects of EPO on the metastatic process. These studies may begin to uncover the underlying functional explanation for the observed EPO-related adverse events and decreased survival in ESA-treated metastatic breast cancer patients undergoing chemotherapy. Clin Cancer Res; 17(19); 6151–62. ©2011 AACR.

Published
2023
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11. Supplementary Figure 1 from Recombinant Human Erythropoietin in Combination with Chemotherapy Increases Breast Cancer Metastasis in Preclinical Mouse Models

Author

Anargyros Xenocostas, Alison L. Allan, Alexandra Boasie, Michel S. Beausoleil, D. George Ormond, Jenny E. Chu, and Benjamin D. Hedley

Abstract

PDF file - 145KB, EPOR and JAK2 amplification was normalized to GAPDH intensity for mBM, UT7/EPO, 3T3, H838, MDA-MB-435, MDA-MB-231, MDA-MB-468 and 4T1 samples, with (*) or without rHuEPO treatment and subjected to densitometric analysis.

Published
2023
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13. Premature Aging and Reduced Cancer Incidence Associated with Body-Wide Loss ofMyc

Author

Huabo Wang, Jie Lu, Taylor Stevens, Alexander Roberts, Jordan Mandel, Raghunandan Avula, Yijen Wu, Jinglin Wang, Clinton Van’t Land, Toren Finkel, Jerry E. Vockley, Merlin Airik, Rannar Airik, Radhika Muzumdar, Zhenwei Gong, Michel S. Torbenson, and Edward V. Prochownik

Abstract

MYC proto-oncogene dysregulation alters metabolic, translational, cell cycle and other functions in ways that support tumor induction and maintenance. Myc+/- mice are healthier and longer-lived than control mice but the long-term ramifications of more complete Myc loss remain unknown. We now describe the life-long consequences of body-wide Myc inactivation initiated post-natally. “MycKO” mice rapidly acquire numerous features of premature aging including altered body composition and habitus, metabolic dysfunction, hepatic steatosis and the dysregulation of numerous gene sets involved in functions that normally deteriorate with aging. Yet, MycKO mice have an extended life span that correlates with a 4-5-fold lower lifetime cancer incidence. Aging tissues from normal mice and humans deregulate many of the same gene sets as do young MycKO mice while also down-regulating Myc and many of its target genes. Normal aging and its associated cancer predisposition are thus highly linked via Myc and its target genes and can be genetically separated.

Published
2023
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15. Home-based exercise program in the indeterminate form of Chagas disease (PEDI-CHAGAS study): A study protocol for a randomized clinical trial

Author

Mauro F. F. Mediano, Leonardo G. Ribeiro, Rudson S. Silva, Isis G. G. Xavier, Marcelo C. Vieira, Tatiana R. Gonçalves, Vitor B. Paravidino, Juliana P. Borges, Luiz Fernando Rodrigues Junior, Henrique S. Costa, Michel S. Reis, Livia C. Liporagi-Lopes, Pablo Martinez-Amezcua, Paula S. Silva, Gilberto M. Sperandio Da Silva, Andrea S. Sousa, Marcelo T. Holanda, Henrique H. Veloso, Fernanda M. Carneiro, Flavia Mazzoli-Rocha, Andrea R. Costa, Roberto M. Saraiva, Fernanda S. N. S. Mendes, Luiz Henrique C. Sangenis, and Alejandro M. Hasslocher-Moreno

Subjects
General Medicine
Abstract

BackgroundChagas disease (CD) is a neglected endemic disease with worldwide impact due to migration. Approximately 50–70% of individuals in the chronic phase of CD present the indeterminate form, characterized by parasitological and/or serological evidence of Trypanosoma cruzi infection, but without clinical signs and symptoms. Subclinical abnormalities have been reported in indeterminate form of CD, including pro-inflammatory states and alterations in cardiac function, biomarkers and autonomic modulation. Moreover, individuals with CD are usually impacted on their personal and professional life, making social insertion difficult and impacting their mental health and quality of life (QoL). Physical exercise has been acknowledged as an important strategy to prevent and control numerous chronic-degenerative diseases, but unexplored in individuals with the indeterminate form of CD. The PEDI-CHAGAS study (which stands for “Home-Based Exercise Program in the Indeterminate Form of Chagas Disease” in Portuguese) aims to evaluate the effects of a home-based exercise program on physical and mental health outcomes in individuals with indeterminate form of CD.Methods and designThe PEDI-CHAGAS is a two-arm (exercise and control) phase 3 superiority randomized clinical trial including patients with indeterminate form of CD. The exclusion criteria are ConclusionThe findings from the present study may support public health intervention strategies to improve physical and mental health parameters to be implemented more effectively in this population.Clinical trial registration[https://ensaiosclinicos.gov.br/rg/RBR-10yxgcr9/], identifier [U1111-1263-0153].

Published
2023
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17. Vibrational and mechanical properties of the highly mismatched (Cd,Be)Te semiconductor alloy : Experiment and ab initio calculations

Author

Elmahjoubi, A., Shoker, M. B., Pages, O., Torres, V. J. B., Polian, A., Postnikov, A. V., Bellin, C., Beneut, K., Gardiennet, C., Kervern, G., EnNaciri, A., Broch, L., Hussein, R. Hajj, Itie, J. -P., Nataf, L., Ravy, S., Franchetti, P., Diliberto, S., Michel, S., Abouais, A., and Strzalkowski, K.

Subjects
Condensed Matter - Materials Science, Materials Science (cond-mat.mtrl-sci), FOS: Physical sciences
Abstract

The (Cd, Be)Te semiconductor alloy that exhibits a dramatic mismatch in bond covalency and stiffness clarifying its vibrational and mechanical properties is used as a benchmark to test the limits of the percolation model (PM) worked out to explain the complex Raman spectra of the related but less contrasted (Zn, Be) chalcogenides. The test is done by way of experiment (x smaller than 0.11) combining Raman scattering with X ray diffraction at high pressure and ab initio calculations (x around 0, 0.5 and 1). The (macroscopic) bulk modulus B drops below the CdTe value on minor Be incorporation, at variance with a linear B versus x increase predicted ab initio, thus hinting at large anharmonic effects in the real crystal. Yet, no anomaly occurs at the microscopic (bond) scale as the regular bimodal PM Raman signal predicted ab initio for the BeTe bond in minority (x around 0 and 0.5) is (barely) detected experimentally. Although at large Be content (x around 1) the same bimodal signal relaxes down to inversion, an unprecedented case, specific pressure dependencies of the regular (x around 0 and 0.5) and inverted (x around 1) BeTe Raman doublets are in line with PM predictions. Hence, the PM applies as such to (Cd, Be)Te albeit in a relaxed form, without further refinement. This enhances the scheme validity as a generic descriptor of phonons in alloys.

Published
2023
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18. Fourth mRNA COVID-19 Vaccination in Immunocompromised Patients with Hematologic Malignancies

Author

Quincy Hofsink, Sabine Haggenburg, Birgit I. Lissenberg-Witte, Annoek E.C. Broers, Jaap A. van Doesum, Robert Samuel van Binnendijk, Gerco den Hartog, Michel S. Bhoekhan, Nienke J.E. Haverkate, Johan van Meerloo, Judith A. Burger, Joey H. Bouhuijs, Gaby Smits, D. Wouters, Ester M.M. van Leeuwen, Hetty J. Bontkes, Neeltje A. Kootstra, Sandra Vogels-Nooijen, Nynke Rots, Josine van Beek, Mirjam HM Heemskerk, Kazimierz Groen, Tom van Meerten, Pim G. N. J. Mutsaers, Marit J. van Gils, Abraham Goorhuis, Caroline E. Rutten, Mette D. Hazenberg, Inger S. Nijhof, and COBRA KAI Study Team

Published
2023
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19. Defence Spending and Sovereign Debt in Greece: A Long-Term Historical Perspective

Author

Suzanna-Maria Paleologou, Michel S. Zouboulakis, and Christos Kollias

Subjects
Economics and Econometrics, Sociology and Political Science, Political Science and International Relations, Perspective (graphical), Economics, Monetary economics, Management, Monitoring, Policy and Law, Sovereign debt, Term (time)
Abstract

The paper sets out to examine the military spending-public debt nexus in the case of Greece. Unlike previous studies that exclusively focus their analyses in the post-WWII period, the empirical investigation conducted herein covers almost the entire two hundred years of the modern Greek state. The estimations using an ARDL framework cover the period 1848–2018 as well as sub-periods therein. To the best of our knowledge, this is the first paper to approach this issue in the case of Greece with such a long-term perspective. In broad terms, the findings do not unearth a statistically traceable effect of defence expenditures on public debt accumulation. The results indicate that this was very much driven by debt dynamics and the need to draw funds to service existing loans. This finding is consistent across both the entire period under scrutiny here as well as the various sub-periods.

Published
2021
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20. The long‐term effects of primary school‐based obesity prevention interventions in children: A systematic review and meta‐analysis

Author

Michel S. Smit, Mirte Boelens, Famke J. M. Mölenberg, Hein Raat, and Wilma Jansen

Subjects
Nutrition and Dietetics, SDG 3 - Good Health and Well-being, Health Policy, Pediatrics, Perinatology and Child Health, Public Health, Environmental and Occupational Health
Abstract

Introduction: This systematic review and meta-analysis investigate the long-term effects of primary school-based obesity prevention interventions on body-mass index (and z-scores), waist circumference (and z-scores) and weight status. Methods: Four databases were searched for studies from date of inception until June 8th, 2021. We included randomized controlled trials (RCT) and non-RCTs investigating effects ≥12 months post-intervention of primary school-based interventions with intervention duration ≥6 months and containing a diet and/or physical activity component on outcomes of interest. Articles were assessed on risk of bias and methodological quality by RoB2 and ROBINS-I. Meta-analysis was performed and results were narratively summarized. Evidence quality was assessed with GRADE. Results: Nineteen studies were included, 9 were pooled in a meta-analysis. No long-term effects were found on body-mass index (+0.06 kg/m2; CI95% = −0.38, 0.50; I2 = 66%), body-mass index z-scores (−0.08; CI95% = −0.20, 0.04; I2 = 36%), and waist circumference (+0.57 cm; CI95% = −0.62, 1.75; I2 = 13%). Non-pooled studies reported mixed findings regarding long-term effects on body-mass index, body-mass index z-scores and weight status, and no effects on waist circumference and waist circumference z-scores. Evidence certainty was moderate to very low. Discussion: No clear evidence regarding long-term effects of primary school-based interventions on obesity-related outcomes was found. Recommendations for further research and policy are discussed. Prospero registration ID: CRD42021240446.

Published
2022
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21. Challenges in selecting admixture models and marker sets to infer genetic ancestry in a Brazilian admixed population

Author

Luciana Maia Escher, Michel S. Naslavsky, Marília O. Scliar, Yeda A. O. Duarte, Mayana Zatz, Kelly Nunes, and Silviene F. Oliveira

Subjects
Multidisciplinary
Abstract

The inference of genetic ancestry plays an increasingly prominent role in clinical, population, and forensic genetics studies. Several genotyping strategies and analytical methodologies have been developed over the last few decades to assign individuals to specific biogeographic regions. However, despite these efforts, ancestry inference in populations with a recent history of admixture, such as those in Brazil, remains a challenge. In admixed populations, proportion and components of genetic ancestry vary on different levels: (i) between populations; (ii) between individuals of the same population, and (iii) throughout the individual's genome. The present study evaluated 1171 admixed Brazilian samples to compare the genetic ancestry inferred by tri-/tetra-hybrid admixture models and evaluated different marker sets from those with small numbers of ancestry informative markers panels (AIMs), to high-density SNPs (HDSNP) and whole-genome-sequence (WGS) data. Analyses revealed greater variation in the correlation coefficient of ancestry components within and between admixed populations, especially for minority ancestral components. We also observed positive correlation between the number of markers in the AIMs panel and HDSNP/WGS. Furthermore, the greater the number of markers, the more accurate the tri-/tetra-hybrid admixture models.

Published
2022
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22. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author

Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly Ohmart, Carmen C Beladan, Carmen Ginghina, Carol M Kartje, Caroline Alsweiler, Caroline Brown, Caroline Callison, Caroline Pinheiro, Caroline Rodgers, Caroline Spindler, Carolyn Corbett, Carrie Drum, Casey Riedberger, Catherine Bone, Catherine Fleming, Catherine Gordon, Catherine Jahrsdorfer, Catherine Lemay, Catherine Weick, Cathrine Patten, Cecilia Goletto, Cezary Kepka, Chandini Suvarna, Chang Xu, Chantale Mercure, Charle A Viljoen, Charlene Wiyarand, Charles Jia-Yin Hou, Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine 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Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C Quinn, Maria A Alfonso, Maria Antonieta Pereira Moraes, María Dolores Martínez-Ruíz, María Fernanda Canales, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Victoria Actis, Maria Aguirre, Maria Andreasson, Maria Aprile, Maria Colton, Maria Eugenia Martin, Maria Lasala, Maria Lorenzo, Maria Posada, Maria Shier, Maria Thottam, Mariana V Furtado, Mariana Yumi Okada, Marianna D A Dracoulakis, Marianne De Andrade, Mariano Rubio, Marie Essermark, Marielle Scherrer-Crosbie, Marija T Petrovic, Marija Zdravkovic, Marilyn Black, Marina Garcia, Mario J Garcia, Mariola Szulik, Marisa Orgera, Mark A de Belder, Mark Harbinson, Mark Hyun, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Marcinkiewicz-Siemion, Marta Swiderek, Martha Meyer, Martina Ceseri, Martina Tricoli, Marvin Kronenberg, Mary Williams, Mary Ann Champagne, Mary Colleen Rogge, Mary R Soltau, Mary Streif, Massimo Villella, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Wall Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Mona Bhatia, Monica Rosca, Monika Laukyte, Montserrat Gracida Blanca, Montserrat Vila Perales, Mouaz H Al-Mallah, Moysés de Oliveira Filho, Mpiko Ntsekhe, Muhamed Saric, Mulei Chen, Myriam Brousseau, Myrthes Emy Takiuti, Nada Cemerlic-Adjic, Nadia Asif, Nadia Gakou, Nafisa Hussain, Nana O Katamadze, Nancy L Clapp, Nancy Aedy, Nandita Nataraj, Nanette K Wenger, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits

Subjects
Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Published
2020
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23. The Amendment of the Wage-Fund Theory and the Legalization of British Trade Unions in 1871

Author

Michel S. Zouboulakis

Subjects
Economics and Econometrics, History, education.field_of_study, media_common.quotation_subject, Population, Wage, Collective action, Royal Commission, Political economy, Capital (economics), Political Science and International Relations, Trade union, Economics, Industrial relations, education, media_common, Legalization
Abstract

Before the Trade Union Act 1871 the legal position of trade unions in the United Kingdom was at best ambiguous, as in many ways they remained outside the law. At the same time, Political Economy maintained that, given a country’s stock of capital and the population of workers, any rise in wages would undermine profits and accumulation. This provided the rationale for politicians and industrialists to argue that wages were not negotiable and that collective action was illegitimate. In reviewing William Thornton’s defence of workers’ right to claim higher wages, John Stuart Mill accepted that the denial of the positive effect of trade unions on wages ‘is deprived of its scientific foundation’. Using evidence from debates in the Royal Commission on Trade Unions, 1867-69, this article examines the extent to which Mill’s acceptance of the economic argument in favour of trade-union collective action contributed to improving the legal status and role of unions in wage bargaining and to change in industrial relations

Published
2021
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24. Follow-up of young adult monozygotic twins after simultaneous critical coronavirus disease 2019: a case report

Author

Mateus V. de Castro, Monize V. R. Silva, Flávia B. Soares, Vivian R. Cória, Michel S. Naslavsky, Marilia O. Scliar, Erick C. Castelli, Jamile R. de Oliveira, Giuliana X. de Medeiros, Greyce L. Sasahara, Keity S. Santos, Edecio Cunha-Neto, Jorge Kalil, and Mayana Zatz

Subjects
General Medicine
Abstract

BackgroundThe influence of the host genome on coronavirus disease 2019 (COVID-19) susceptibility and severity is supported by reports on monozygotic (MZ) twins where both were infected simultaneously with similar disease outcomes, including several who died due to the SARS-CoV-2 infection within days apart. However, successive exposures to pathogens throughout life along with other environmental factors make the immune response unique for each individual, even among MZ twins.Case presentation and methodsHere we report a case of a young adult monozygotic twin pair, who caught attention since both presented simultaneously severe COVID-19 with the need for oxygen support despite age and good health conditions. One of the twins, who spent more time hospitalized, reported symptoms of long-COVID even 7 months after infection. Immune cell profile and specific responses to SARS-CoV-2 were evaluated as well as whole exome sequencing.ConclusionAlthough the MZ twin brothers shared the same genetic mutations which may be associated with their increased risk of developing severe COVID-19, their clinical progression was different, reinforcing the role of both immune response and genetics in the COVID-19 presentation and course. Besides, post-COVID syndrome was observed in one of them, corroborating an association between the duration of hospitalization and the occurrence of long-COVID symptoms.

Published
2022
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25. The association of exercise test variables with long-term mortality in patients with chronic Chagas disease

Author

Rudson S. Silva, Fernanda S. N. S. Mendes, Jerome L. Fleg, Luiz F. Rodrigues Junior, Marcelo C. Vieira, Isis G. G. Xavier, Henrique S. Costa, Michel S. Reis, Flavia Mazzoli-Rocha, Andrea R. Costa, Marcelo T. Holanda, Henrique H. Veloso, Gilberto M. Sperandio da Silva, Andréa S. Sousa, Roberto M. Saraiva, Alejandro Marcel Hasslocher-Moreno, and Mauro F. F. Mediano

Subjects
General Medicine
Abstract

BackgroundThe identification of variables obtained in the exercise test (ET) associated with increased risk of death is clinically relevant and would provide additional information for the management of Chagas disease (CD). The objective of the present study was to evaluate the association of ET variables with mortality in patients with chronic CD.MethodsThis retrospective longitudinal observational study included 232 patients (median age 46.0 years; 50% women) with CD that were followed at the Evandro Chagas National Institute of Infectious Diseases (Rio de Janeiro, Brazil) and performed an ET between 1989 and 2000. The outcome of interest was all-cause mortality.ResultsThere were 103 deaths (44.4%) during a median follow-up of 21.5 years (IQR 25–75% 8.0–27.8), resulting in 24.5 per 1,000 patients/year incidence rate. The ET variables associated with mortality after adjustments for potential confounders were increased maximal (HR 1.02; 95% CI 1.00–1.03 per mmHg) and change (HR 1.03; 95% CI 1.01–1.06 per mmHg) of diastolic blood pressure (DBP) during ET, ventricular tachycardia at rest (HR 3.95; 95% CI 1.14–13.74), during exercise (HR 2.73; 95% CI 1.44–5.20), and recovery (HR 2.60; 95% CI 1.14–5.91), and premature ventricular complexes during recovery (HR 2.06; 1.33–3.21).ConclusionOur findings suggest that ET provides important prognostic value for mortality risk assessment in patients with CD, with hemodynamic (increased DBP during exercise) and electrocardiographic (presence of ventricular arrhythmias) variables independently associated with an increased mortality risk in patients with CD. The identification of individuals at higher mortality risk can facilitate the development of intervention strategies (e.g., close follow-up) that may potentially have an impact on the longevity of patients with CD.

Published
2022
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26. COVID-Associated Acute Limb Ischemia During the Delta Surge And The Effect Of Vaccines

Author

Bowen Xie, Dana B. Semaan, Mary A. Binko, Nishant Agrawal, Rohan N. Kulkarni, Elizabeth A. Andraska, Ulka Sachdev, Rabih A. Chaer, Mohammad H. Eslami, Michel S. Makaroun, and Natalie Sridharan

Subjects
Surgery, Cardiology and Cardiovascular Medicine
Abstract

Hypercoagulability is common in SARS-CoV-2 and has been associated with arterial thrombosis leading to acute limb ischemia (ALI). Our objective was to determine the outcomes of concurrent COVID-19 infection and ALI, particularly during the Delta variant surge and the impact of vaccination status.A retrospective review was performed of patients treated at a single healthcare system between March 2020 and December 2021 for ALI and recent (14 days) COVID-19 infection or who developed ALI during hospitalization for the same disease. Patients were grouped by year as well as by pre and post Delta variant emergence in 2021 based on WHO timeline (January-May vs. June-December). Baseline demographics, imaging, interventions, and outcomes were evaluated. A control cohort of all ALI patients requiring surgical intervention for a two-year period prior to the pandemic was used for comparison. Primary outcomes were in-hospital mortality and amputation-free survival. Kaplan-Meier survival and Cox proportional hazards analysis were performed.40 acutely ischemic limbs were identified in 36 patients with COVID-19, the majority during the Delta surge (52.8%) and after the wide availability of vaccines. The rate of COVID-19 associated ALI, though low overall, nearly doubled during the Delta surge (0.37% vs. 0.20%, p-value=.09). Baseline demographics and comorbidities are summarized in Table 1. Intervention (open or endovascular revascularization vs. primary amputation) was performed on 31 limbs in 28 individuals with the remaining 8 treated with systemic anti-coagulation. Post-operative mortality was 48% and overall mortality was 50%. Major amputation following revascularization was significantly higher with COVID ALI (25% vs. 3%, p=0.006) compared to the pre-pandemic group. 30-day amputation-free survival was significantly lower (log-rank p0.001). COVID infection (aHR=6.2, p0.001) and age (HR=1.1, p=0.006) were associated with 30-day amputation in multivariate analysis. Severity of COVID infection, defined as vasopressor usage, was not associated with post-revascularization amputation. There was a higher incidence of re-thrombosis in the latter half of 2021 with the Delta surge as reintervention for recurrent ischemia of the same limb was more common than our previous experience (21% vs. 0%, p=0.55). COVID-19 associated limb ischemia occurred almost exclusively in non-vaccinated patients (92%).ALI observed with Delta appears more resistant to standard therapy. Unvaccinated status correlated highly with ALI occurrence in the setting of COVID-19 infection. Information of limb loss as a COVID complication among non-vaccinated may help to increase compliance.

Published
2022

27. Genetic Ancestry Inference: from AIMS to WGS application and challenges in admixed population

Author

Luciana M Escher, Michel S Naslavsky, Marília O Scliar, Yeda A O Duarte, Mayana Zatz, Kelly Nunes, and Silviene F Oliveira

Abstract

Increasingly, the inference of genetic ancestry plays a prominent role in clinical, population and forensic genetics studies. Over the last few decades, several genotyping strategies and analytical methodologies have been developed in order to assign individuals to specific biogeographic regions. However, despite all these efforts, the ancestry inference in populations with a recent history of admixture, such as those in America, is still a challenge. In admixed populations, proportion and components of genetic ancestry vary at different levels: (i) between populations; (ii) between individuals of the same population; (iii) throughout the individual's genome. In the present study we compared and evaluated different sets of markers, from those with small numbers of ancestry informative markers panels (AIMs), to high-density SNPs (HDSNP) and whole-genome-sequence (WGS) data. To this end, we evaluated 1,675 admixed samples from America, using a tetrahybrid admixture model (Native American, European, African and East Asian). Analyses show greater variation in the correlation coefficient of ancestry components within and between admixed populations, especially for minority ancestral components. We also observed, the higher the number of markers in the AIMs panel, the higher the correlation with HDSNP and WGS. In addition, the greater the number of markers, the more robust was the tetrahybrid admixture model.

Published
2022
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28. Challenges in selecting admixture models and marker sets to infer genetic ancestry in a Brazilian admixed population

Author

Luciana Maia, Escher, Michel S, Naslavsky, Marília O, Scliar, Yeda A O, Duarte, Mayana, Zatz, Kelly, Nunes, and Silviene F, Oliveira

Abstract

The inference of genetic ancestry plays an increasingly prominent role in clinical, population, and forensic genetics studies. Several genotyping strategies and analytical methodologies have been developed over the last few decades to assign individuals to specific biogeographic regions. However, despite these efforts, ancestry inference in populations with a recent history of admixture, such as those in Brazil, remains a challenge. In admixed populations, proportion and components of genetic ancestry vary on different levels: (i) between populations; (ii) between individuals of the same population, and (iii) throughout the individual's genome. The present study evaluated 1171 admixed Brazilian samples to compare the genetic ancestry inferred by tri-/tetra-hybrid admixture models and evaluated different marker sets from those with small numbers of ancestry informative markers panels (AIMs), to high-density SNPs (HDSNP) and whole-genome-sequence (WGS) data. Analyses revealed greater variation in the correlation coefficient of ancestry components within and between admixed populations, especially for minority ancestral components. We also observed positive correlation between the number of markers in the AIMs panel and HDSNP/WGS. Furthermore, the greater the number of markers, the more accurate the tri-/tetra-hybrid admixture models.

Published
2022

29. Biased pathogenic assertions of loss of function variants challenge molecular diagnosis of admixed individuals

Author

Eduardo Tarazona-Santos, Heinner Guio, Jaqueline Y. T. Wang, Yeda Aparecida de Oliveira Duarte, Marilia O. Scliar, Michel S Naslavsky, Guilherme L. Yamamoto, Diogo Meyer, Maria Rita Passos-Bueno, Mayana Zatz, and Kelly Nunes

Subjects
Prioritization, Population, Biology, Genetics, Humans, Exome, underrepresented populations, Allele, education, Mendelian disorders, Genetics (clinical), Loss function, Exome sequencing, Aged, Whole genome sequencing, education.field_of_study, Genetic Variation, High-Throughput Nucleotide Sequencing, Genomics, pathogenic assertions, whole-genome sequencing, NEOPLASIAS, Cohort, admixture, pLOF, Brazil
Abstract

Diagnosis of individuals affected by monogenic disorders was significantly improved by next-generation sequencing targeting clinically relevant genes. Whole exomes yield a large number of variants that require several filtering steps, prioritization, and pathogenicity classification. Among the criteria recommended by ACMG, those that rely on population databases critically affect analyses of individuals with underrepresented ancestries. Population-specific allelic frequencies need consideration when characterizing potential deleteriousness of variants. An orthogonal input for classification is annotation of variants previously classified as pathogenic as a criterion that provide supporting evidence widely sourced at ClinVar. We used a whole-genome dataset from a census-based cohort of 1,171 elderly individuals from São Paulo, Brazil, highly admixed, and unaffected by severe monogenic disorders, to investigate if pathogenic assertions in ClinVar are enriched with higher proportions of European ancestry, indicating bias. Potential loss of function (pLOF) variants were filtered from 4,250 genes associated with Mendelian disorders and annotated with ClinVar assertions. Over 1,800 single nucleotide pLOF variants were included, 381 had non-benign assertions. Among carriers (N = 463), average European ancestry was significantly higher than noncarriers (N = 708; p = .011). pLOFs in genomic contexts of non-European local ancestries were nearly three times less likely to have any ClinVar entry (OR = 0.353; p

Published
2021
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30. Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass and fat mass indexes

Author

Meddly L. Santolalla, Fernanda S G Kehdy, Thiago P. Leal, Michel S Naslavsky, Meredith Yeager, Moara Machado, Eduardo Tarazona-Santos, Shane A. Norris, Hanaisa P Sant'Anna, Francisco Pereira Lobo, Victor Borda, Lucas Michelin, Alexandre C. Pereira, Sam M. Mbulaiteye, Robert H. Gilman, Guilherme L. Yamamoto, Edward D. Yeboah, Marcelo R. Luizon, Matthew E. B. Hansen, Sérgio Viana Peixoto, Camila Zolini, Nathalia M. Araujo, Julie Dutil, Timothy D O Connor, Isabela Alvim, Mateus H. Gouveia, Maria Rita Passos-Bueno, Ricardo Lyra, Marilia O. Scliar, Michèle Ramsay, Gilderlanio S. Araújo, Yeda Aparecida de Oliveira Duarte, Heinner Guio, Mayana Zatz, Maria Fernanda Lima-Costa, Wagner C. S. Magalhães, Sarah A. Tishkoff, Ananyo Choudhury, Bernardo L. Horta, Maíra R. Rodrigues, James E. Mensah, Mauricio Lima Barreto, and Ann W. Hsing

Subjects
Male, purl.org/pe-repo/ocde/ford#3.03.04 [https], Endocrinology, Diabetes and Metabolism, Population, Medicine (miscellaneous), Genetic admixture, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, Regulatory Sequences, Nucleic Acid, Biology, Polymorphism, Single Nucleotide, Article, Body Mass Index, Young Adult, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Genetics, Humans, 030212 general & internal medicine, Allele, Young adult, Child, education, Alleles, Aged, Aged, 80 and over, education.field_of_study, Nutrition and Dietetics, purl.org/pe-repo/ocde/ford#3.02.18 [https], Chromosome Mapping, Middle Aged, Genetic architecture, Genetics, Population, Phenotype, Risk factors, Child, Preschool, Cohort, Female, Body mass index, Brazil, Demography
Abstract

Background/objectives: Admixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely underrepresented in genomic studies. Here, we study the genetic architecture of BMI in children, young adults, and elderly individuals from the admixed population of Brazil. Subjects/methods: Leveraging admixture in Brazilians, whose chromosomes are mosaics of fragments of Native American, European, and African origins, we used genome-wide data to perform admixture mapping/fine-mapping of body mass index (BMI) in three Brazilian population-based cohorts from Northeast (Salvador), Southeast (Bambui), and South (Pelotas). Results: We found significant associations with African-associated alleles in children from Salvador (PALD1 and ZMIZ1 genes), and in young adults from Pelotas (NOD2 and MTUS2 genes). More importantly, in Pelotas, rs114066381, mapped in a potential regulatory region, is significantly associated only in females (p = 2.76e-06). This variant is rare in Europeans but with frequencies of similar to 3% in West Africa and has a strong female-specific effect (95% CI: 2.32-5.65 kg/m(2) per each A allele). We confirmed this sex-specific association and replicated its strong effect for an adjusted fat mass index in the same Pelotas cohort, and for BMI in another Brazilian cohort from Sao Paulo (Southeast Brazil). A meta-analysis confirmed the significant association. Remarkably, we observed that while the frequency of rs114066381-A allele ranges from 0.8 to 2.1% in the studied populations, it attains similar to 9% among women with morbid obesity from Pelotas, Sao Paulo, and Bambui. The effect size of rs114066381 is at least five times higher than the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects. Conclusions: We identified six candidate SNPs associated with BMI. rs114066381 stands out for its high effect that was replicated and its high frequency in women with morbid obesity. We demonstrate how admixed populations are a source of new relevant phenotype-associated genetic variants.

Published
2021
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31. Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study

Author

David Adams, Michael Polydefkis, Alejandra González-Duarte, Jonas Wixner, Arnt V Kristen, Hartmut H Schmidt, John L Berk, Inés Asunción Losada López, Angela Dispenzieri, Dianna Quan, Isabel M Conceição, Michel S Slama, Julian D Gillmore, Theodoros Kyriakides, Senda Ajroud-Driss, Márcia Waddington-Cruz, Michelle M Mezei, Violaine Planté-Bordeneuve, Shahram Attarian, Elizabeth Mauricio, Thomas H Brannagan, Mitsuharu Ueda, Emre Aldinc, Jing Jing Wang, Matthew T White, John Vest, Erhan Berber, Marianne T Sweetser, Teresa Coelho, Giuseppe Vita, Vincenzo Rizzo, Massimo Russo, Anna Mazzeo, Luca Gentile, Caitlin Brueckner, Victoria Lazzari, Janice Wiesman, Douglas DeLong, Jennifer Victory, James Dalton, John May, Catherine Gilmore, Saran Diallo, Emilien Delmont, Jean Pouget, Annie Verschueren, Aude-Marie Grapperon, Emmanuelle Campana-Salort, Ana Lopes, Filipa Lamas, Carlos Neves, Jose Castro, Pedro Pereira, Isabel Castro, Ana Franco, Miguel Oliveira Santos, Conceição de Azevedo Coutinho, Catarina Falcao de Campos, Antonio Hipólito Reis, Nuno Correia, Javier M Perez, Ana Martins da Silva, Cristina Alves, Marcio Cardoso, Katia Valdrez, Julia R Monte, Bernardete Pessoa, Nadia Guimaraes, Monica Freitas, Joana Ramalho, Natalia Ferreira, Daisuke Kuzume, Celine Tard, Nawal Waucquier, Isabelle Rougeaux, Sylvie Brice, Emmanuelle Kasprzyk, Elise Elrezzi, Sayah Meguig, Eric Hachulla, Clement Gauvain, Maria-Claire Migaud-Chervy, Dominique Deplanque, Elsa Jozefowicz, Loic Lebellec, Line Balaya-Gouraya, Nathalie Jehan Lacour, Halima Bournane, Nathalie Martin, Mongia Elabed, Niamey Sacko, Yasmine Boubrit, Amina Gaouar, Fetra Rakotondratafika, Marie Théaudin-Saliou, Cécile Cauquil-Michon, Celine Labeyrie, Adeline Not, Abdallah Al-Salameh, Anne-Lise Lecoq, Maeva Stephant, Andoni Echaniz-Laguna, Laurent Becquemont, Guillemette Beaudonnet, Vincent Algalarrondo, Ludivine Eliahou, Antoine Rousseau, Aissatou Signate, Emeline Berthelot, Jocelyn Inamo, Laetitia Vervoitte, Cecile Focseneanu, Thierry Gendre, Raphaele Arrouasse, Samar S. Ayache, Laura Ernande, Philippe Le Corvoisier, Hayet Salhi, Ariane Choumert, Vincent Ehinger, Julie Ruiz, Cyril Charlin, Thomas Megelin, Thomas H Brannagan III, Raisy Fayerman, Arreum Kim, Allan Paras, Leidy J Gonzalez, Steven Tsang, Fernanda Wajnsztajn, Jeffrey Shije, Christina Ulane, Inna Kleyman, Louis Weimer, Comana Cioroiu, Sakis Lambrianides, Rana Abu-Manneh, Eleni Zamba-Papanicolaou, Petros Agathangelou, Eleni Leonidou, Satoshi Tada, Akemi Fujita, Masahiro Nagai, Rina Ando, Yuko Hosokawa, Yuki Yamanishi, J. Scott Overcash, Elena Giardino, Leslie Boyer, Lien Dang, An Le, Tyler Nguyen, Lien Giang, Peter Sellers, Leyla Tran, Nghi Truong, Maita Vinas, Nicole Hrkman, Sarah Miller, David Nguyen, Ashley Smith, Helen Pu, Steve Li, Thao Vuong, Holly Dioso, Sinikka Green, Kia Lee, Hanh Chu, Michael Waters, Derya J Coskun, Karla A Zepeda, William O'Riordan, Laura Obici, Andrea Cortese, Alessandro Lozza, Giampaolo Merlini, Vittorio Rosti, Mario Sabatelli, Giulia Bisogni, Daniela Bernardo, Marco Luigetti, Andrea Di Paolantonio, Valeria Guglielmino, Angela Romano, Hans Nienhuis, Janita Bulthuis-Kuiper, Olga Gerk, Hannah Ulbricht, Lenka Taylor, Eva Meyle, Natalia Kleinschmidt, David Meyrath, Simone Noe-Schwenn, Ulrike Meng, Ralf Bauer, Fabian aus dem Siepen, Selina Hein, Tetsuya Takahashi, Tomohiko Oshita, Yoko Koujin, Shuichiro Neshige, Tomohisa Nezu, Akiko Segawa, Hiroki Ueno, Hiroyuki Morino, Josep M Campistol, Lida Maria Rodas Marin, Josep Miquel Blasco Pelicano, Lucía Galán Dávila, Marta Palacios, Vanesa Pytel Cordoba, Antonio Guerrero Sola, Alejandro Horga, Julián García Feijoo, Leopoldo Perez de Isla, Wilson Marques Júnior, Mariana Moscardini, Debora Cristina Litcanov, Ana Flavia Viera Lima, Leonardo Rodrigues, Barbara Marques Coutinho, Carolina Lavigne Moreira, Vanessa Daccach Marques, Francisco Munoz Beamud, Álvaro Gragera Martínez, Cristina Borrachero, Eugenia Cisneros Barroso, Adrián Rodríguez Rodríguez, Monica Sanz, Elena Rigo Oliver, Juan González Moreno, Jose M Gamez Martinez, Cristina Descals, Mercedes Uson, Francisco Jose Vega, Antoni Figuerola, Carles Montala, Moises Dias da Silva, Renata Gervais de Santa Rosa, Luiz Felipe Pinto, Marcus Vinicius Pinto, Amanda Cardoso Berensztejn, Fabio Barroso, Andrea Lautre, Lucas G Orellana, Maria Alejandra González-Duarte Briseño, Karla Cárdenas-Soto, Brenda Poled Jiménez López, Sandra Lorena Pérez-Castañeda, Carlos Gerardo Cantú Brito, David Rivera de la Parra, Jose Pablo Hernandez Reyes, Maria del Mar Saniger Alba, Elia Criollo Mora, Yesim Parman, Kus Jülide Rezzan, Erdi Sahin, Nail G Serbest, Hacer Durmus, Arman Cakar, Nuriye Ilknur Tugal Tutkun, Sacit Karamursel, Ali Elitok, Nermin G Sirin Inan, Emre Altinkurt, Jing Ye, Adriane C Allen, Vinay Chaudhry, Raquel Jarrett, Neil Bressler, Kathleen L Burks, Qingfeng Liu, Mohammad Khoshnoodi, Daniel P Judge, Geno Vista, Syed Mahmood Shah, Hirotoshi Hamaguchi, Junko Oda, Emi Fukase, Ikuko Taniguchi, Tetsuya Oda, Hironobu Endo, Masahiro Shimomura, Kimitaka Katanazaka, Shusuke Koto, Takahiro Nakano, Christof Scheid, Andreas Zueiter, Lars Pester, Doreen Walter, Betül Özdemir, Lukas F Frenzel, Udo Holtick, Jeeyoung Oh, Hee Jin Kim, Hyun Jin Shin, Kyomin Choi, Taro Yamashita, Teruaki Masuda, Yohei Misumi, Akihiko Ueda, Keiichi Nakahara, Akiko Yorita, Seiko Tsuruhisa, Takayuki Taniwaki, Masaya Harada, Taiga Moritaka, Naonori Sakurada, Elizabeth A Mauricio, Amber Baskin, Elliot Dimberg, Amie Fonder, Miriam Hobbs, Stephen J Russell, Peter Dyck, Wilson Gonsalves, Nelson Leung, Thomas E Witzig, Steven R Zeldenrust, Lisa Hwa, Prashant Kapoor, Shaji K Kumar, Yi Lin, John A Lust, Vincent S Rajkumar, David Dingli, Morie A Gertz, Ronald Go, Suzanne R Hayman, Samir Dalia, Esmeralda Carrillo, Peter Gorevic, Garnette Mason, Chi-Chao Chao, Ming-Jen Lee, Jen-Jen Su, Sung-Tsang Hsieh, Li-Kai Tsai, Shin-Joe Yeh, Chih-Chao Yang, Senda Ajroud-Driss Ajroud-Driss, Patricia Casey, Benjamin C Joslin, Miriam Freimer, Alison Sankey, Amanda Kenepp, Sarah Heintzman, Samantha LoRusso, Youichi Hokezu, Byoung-Joon Kim, JuHyeon Kim, Ga Yeon Lee, Eun Bin Cho, Eun-Seok Jeon, Ju-Hong Min, Jin Myoung Seok, Hye Lim Lee, Jae Hong Park, Yoshiki Sekijima, Chinatsu Miyazawa, Nagaaki Kato, Dai Kishida, Akiyo Hineno, Minori Kodaira, Tsuneaki Yoshinaga, Teruyoshi Miyahara, Akira Imai, Kazuhiko Matsumoto, Kon-Ping Lin, Yi-Chung Lee, Malin Falk, Bjorn Pilebro, Ole Suhr, Per Lindqvist, Karin Soderberg, Fatima Pedrosa-Domellöf, Intissar Anan, Erik Nordh, Ivaylo Tournev, Sashka Zhelyazkova-Glaveeva, Zheyna Cherneva, Staiko Sarafov, Teodora Chamova, Sylvia Cherninkova-Gopina, Frauke Friebel, Andree Zibert, Natasa Mihailovic, Friederike Schubert, Elena Vorona, Larissa Lahme, Anna Huesing-Kabar, Matthias Schilling, Iyad Kabar, Ana Martinez-Naharro, Liza Chacko, Oliver Cohen, Steven Law, Tamer Rezk, Helen J Lachmann, Brianna Blume, Stacy Dixon, Soon Chai Low, Soo Looi Chan, He Eng Li Lim, Khean Jin Goh, Deborah Kraus, Kristin Jack, N. Kevin Wade, Glenn Lopate, Brittany Zwijack, Julaine Florence, R. Brian Sommerville, Graeme Stewart, Julie Ryder, Linda Mekhael, Mark Taylor, Daniel Suan, Karen Wells, Paula Stone, Amenze Itoya, Mercy Owusu-Sekyere, Desmond Thai, Ilonah Chahine, Salve Pedrosa, Thi Hoa (Therese) Do, and Repositório da Universidade de Lisboa

Subjects
Adult, Male, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, 030204 cardiovascular system & hematology, Placebo, Severity of Illness Index, Polyneuropathies, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, Outcome Assessment, Health Care, Severity of illness, medicine, Humans, Prealbumin, RNA, Small Interfering, Infusions, Intravenous, Adverse effect, Aged, Amyloid Neuropathies, Familial, business.industry, Middle Aged, medicine.disease, Interim analysis, amyloidosis, transthyretin, polyneuropathy, patisiran, OLE study, Clinical trial, Female, Neurology (clinical), business, Polyneuropathy, 030217 neurology & neurosurgery, Progressive disease
Abstract

© 2020 Elsevier Ltd. All rights reserved., Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.

Published
2021
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33. MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil

Author

Erick C. Castelli, Mateus V. de Castro, Michel S. Naslavsky, Marilia O. Scliar, Nayane S. B. Silva, Raphaela N. Pereira, Viviane A. O. Ciriaco, Camila F. B. Castro, Celso T. Mendes-Junior, Etiele de S. Silveira, Iuri M. de Oliveira, Eduardo C. Antonio, Gustavo F. Vieira, Diogo Meyer, Kelly Nunes, Larissa R. B. Matos, Monize V. R. Silva, Jaqueline Y. T. Wang, Joyce Esposito, Vivian R. Cória, Jhosiene Y. Magawa, Keity S. Santos, Edecio Cunha-Neto, Jorge Kalil, Raul H. Bortolin, Mário Hiroyuki Hirata, Luiz P. Dell’Aquila, Alvaro Razuk-Filho, Pedro B. Batista-Júnior, Amaro N. Duarte-Neto, Marisa Dolhnikoff, Paulo H. N. Saldiva, Maria Rita Passos-Bueno, and Mayana Zatz

Subjects
IDOSOS, HLA-A Antigens, SARS-CoV-2, Immunology, Genes, MHC Class II, Immunology and Allergy, Humans, COVID-19, Brazil, Aged
Abstract

BackgroundAlthough aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome.MethodsSARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started.ResultsWe found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins’ family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24).ConclusionSince the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.

Published
2022

35. The oldest unvaccinated Covid-19 survivors in South America

Author

Mateus V. de Castro, Monize V. R. Silva, Michel S. Naslavsky, Marilia O. Scliar, Kelly Nunes, Maria Rita Passos-Bueno, Erick C. Castelli, Jhosiene Y. Magawa, Flávia L. Adami, Ana I. S. Moretti, Vivian L. de Oliveira, Silvia B. Boscardin, Edecio Cunha-Neto, Jorge Kalil, Emmanuelle Jouanguy, Paul Bastard, Jean-Laurent Casanova, Mauricio Quiñones-Vega, Patricia Sosa-Acosta, Jéssica de S. Guedes, Natália P. de Almeida, Fábio C. S. Nogueira, Gilberto B. Domont, Keity S. Santos, and Mayana Zatz

Subjects
Aging, Immunology
Abstract

Background Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated. Results Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN. Conclusion These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.

Published
2022

37. Three-dose mRNA-1273 vaccination schedule: sufficient antibody response in majority of immunocompromised hematology patients

Author

Sabine Haggenburg, Quincy Hofsink, Birgit I. Lissenberg-Witte, Annoek E.C. Broers, Jaap A. van Doesum, Rob S. van Binnendijk, Gerco den Hartog, Michel S. Bhoekhan, Nienke J.E. Haverkate, Judith A. Burger, Joey H. Bouhuijs, Gaby P. Smits, Dorine Wouters, Ester M.M. van Leeuwen, Hetty J. Bontkes, Neeltje A. Kootstra, Sonja Zweegman, Arnon P. Kater, Mirjam H.M. Heemskerk, Kaz Groen, Tom van Meerten, Pim G.N.J. Mutsaers, Tim Beaumont, Marit J. van Gils, Abraham Goorhuis, Caroline E. Rutten, Mette D. Hazenberg, and Inger S. Nijhof

Subjects
hematology
Abstract

ImportanceIn patients with hematologic malignancies, the immunogenicity of the standard 2-dose mRNA-1273 coronavirus disease 19 (COVID-19) vaccination schedule is often insufficient due to underlying disease and current or recent therapy.ObjectiveTo determine whether a 3rd mRNA-1273 vaccination raises antibody concentrations in immunocompromised hematology patients to levels obtained in healthy individuals after the standard 2-dose mRNA-1273 vaccination schedule.DesignProspective observational cohort study.SettingFour academic hospitals in the Netherlands.Participants584 evaluable immunocompromised hematology patients, all grouped in predefined cohorts spanning the spectrum of hematologic malignancies.ExposureOne additional vaccination with mRNA-1273 5 months after completion of the standard 2-dose mRNA-1273 vaccination schedule.Main Outcomes and MeasuresSerum IgG antibodies to spike subunit 1 (S1) antigens prior to and 4 weeks after each vaccination, and pseudovirus neutralization of wildtype, delta and omicron variants in a subgroup of patients.ResultsIn immunocompromised hematology patients, a 3rd mRNA-1273 vaccination led to median S1 IgG concentrations comparable to concentrations obtained by healthy individuals after the 2-dose mRNA-1273 schedule. The rise in S1 IgG concentration after the 3rd vaccination was most pronounced in patients with a recovering immune system, but potent responses were also observed in patients with persistent immunodeficiencies. Specifically, patients with myeloid malignancies or multiple myeloma, and recipients of autologous or allogeneic hematopoietic cell transplantation (HCT) reached median S1 IgG concentrations similar to those obtained by healthy individuals after a 2-dose schedule. Patients on or shortly after rituximab therapy, CD19-directed chimeric antigen receptor T cell therapy recipients, and chronic lymphocytic leukemia patients on ibrutinib were less or unresponsive to the 3rd vaccination. In the 27 patients who received cell therapy between the 2nd and 3rd vaccination, S1 antibodies were preserved, but a 3rd mRNA-1273 vaccination did not significantly enhance S1 IgG concentrations except for multiple myeloma patients receiving autologous HCT. A 3rd vaccination significantly improved neutralization capacity per antibody.Conclusions and RelevanceThe primary schedule for immunocompromised patients with hematologic malignancies should be supplemented with a delayed 3rd vaccination. B cell lymphoma patients and allogeneic HCT recipients need to be revaccinated after treatment or transplantation.Trial RegistrationEudraCT 2021-001072-41Key pointsQuestionCan a 3rd mRNA-1273 vaccination improve COVID-19 antibody concentrations in immunocompromised hematology patients to levels similar to healthy adults after the standard 2-dose mRNA-1273 schedule?FindingsIn this prospective observational cohort study that included 584 immunocompromised hematology patients, a 3rd mRNA-1273 vaccination significantly improved SARS-CoV-2 antibody concentrations to levels not significantly different from those obtained by healthy individuals after the standard 2-dose mRNA-1273 vaccination schedule. Pseudovirus neutralization capacity per antibody of wild type virus and variants of concern also significantly improved.MeaningThe primary COVID-19 vaccination schedule for immunocompromised patients with hematologic malignancies should be supplemented with a delayed 3rd vaccination.

Published
2022
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38. Coronacrisis and Coronabonds: Europe’s Survival Game

Author

Michel S. Zouboulakis

Subjects
education.field_of_study, Ebola virus, History, Population, medicine.disease_cause, medicine.disease, Cholera, First world war, Chinese city, Pandemic, Case fatality rate, medicine, Socioeconomics, China, education
Abstract

The entire planet lives in a global crisis. It started as a local health problem in a Chinese city and became rapidly a world pandemic. Yet, pandemics are far from new throughout history. Bubonic Plague (known as Black Death) also arrived from China and decimated half of Europe’s population from 1346 to 1351. Cholera pandemics occurred seven times from 1817 to 1961. Spanish Flu of 1918 killed almost 40 mn people within three years, twice as much as the First World War. AID Syndrome started in 1982 and killed some 1 m people only in 2018, according to the WHO. More recently, in 2014 the Ebola virus disease terrified the world with a fatality rate of 50%. What is new about the actual health crisis is not its duration, neither the number of cases, nor the number of deaths. Coronavirus hits 213 countries (20 more than the UN member states) creating socio-economic problems to all of them, to a different extent. Overall, the negative impact of corona-crisis refer both to the supply side (due to the broken international chains of value) and the demand side (due to the income losses of all those who lost their jobs or incomes).

Published
2020
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39. Uma Pesquisa-Ação no Contexto de Processos de Engenharia de Requisitos em uma Instituição Pública Brasileira

Author

Michel S. Soares and Luís E. S. Santos

Subjects
0202 electrical engineering, electronic engineering, information engineering, 020207 software engineering, 02 engineering and technology, 020202 computer hardware & architecture
Abstract

A Engenharia de Requisitos se destaca como uma fase fundamental na Engenharia de Software por instituir uma visão estrita e comum entre o cliente e a equipe do projeto sobre os requisitos do software a ser desenvolvido. Este estudo foi realizado utilizando a metodologia de pesquisa-ação em uma instituição pública, com objetivo de propor e aplicar um processo para elicitação e documentação de requisitos em nível de usuário. No processo, um modelo foi usado para documentar os requisitos usando a SysML (Systems Modeling Language). No estudo foi realizada uma avaliação qualitativa e quantitativa para avaliar a eficácia do processo. Os resultados sugerem que a intervenção alcançou resultados positivos, incluindo evidências de melhorias na elicitação e documentação dos requisitos do usuário.

Published
2020
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40. Climate Change: Risky Business?

Author

Lara Esther Lázaro Touza and Michel S. Zoghby

Subjects
Economics and Econometrics, Political science, Humanities
Abstract

El quinto informe del IPCC, recientemente publicado, afirma que el cambio climatico es inequivoco, sin precedentes y antropogenico en origen. El cambio climatico como externalidad global tiene consecuencias para el medio ambiente, la economia, la sociedad y la politica. Dichas consecuencias podrian desencadenar perdidas ‘catastroficas’ de bienestar si se sobrepasan determinados puntos criticos. Es posible argumentar que las acciones para evitar dichos resultados catastroficos deberian asemejarse a las decisiones relativas a la adquisicion de seguros, que evitan las peores consecuencias de eventos catastroficos, mas que a decisiones sobre inversiones. Las recomendaciones historicas de seguir una politica de mitigacion gradual han sido parcialmente desbancadas por llamadas mas contundentes a la accion debido a la existencia de eventos extremos. Los esfuerzos de la comunidad internacional hasta la fecha han sido insuficientes para responder a las llamadas urgentes a la accion. La investigacion de eventos extremos, el desarrollo de tecnologias respetuosas con el entorno y los acuerdos de reparto de carga aceptables para los distintos paises, podrian favorecer una accion climatica efectiva y eficiente.

Published
2020
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42. Nationwide trends in drug-coated balloon and drug-eluting stent utilization in the femoropopliteal arteries

Author

Zein Saadeddin, Abhisekh Mohapatra, Michael C. Madigan, Mohammad H. Eslami, Michel S. Makaroun, Georges E. Al-Khoury, and Daniel J. Bertges

Subjects
Male, medicine.medical_specialty, Atherectomy, medicine.medical_treatment, 030204 cardiovascular system & hematology, Balloon, Article, Lesion, Peripheral Arterial Disease, 03 medical and health sciences, 0302 clinical medicine, Coated Materials, Biocompatible, Angioplasty, medicine.artery, medicine, Humans, Popliteal Artery, 030212 general & internal medicine, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Stent, Drug-Eluting Stents, Middle Aged, United States, Popliteal artery, Surgery, Femoral Artery, medicine.anatomical_structure, Drug-eluting stent, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Equipment and Supplies Utilization, Angioplasty, Balloon, Artery
Abstract

Drug-coated balloons (DCB) and drug-eluting stents (DES) have significantly altered treatment paradigms for femoropopliteal lesions. We aimed to describe changes in practice patterns as a result of the infusion of these technologies into the treatment of peripheral arterial disease.We queried the Vascular Quality Initiative registry from 2010 to 2017 for all peripheral vascular interventions involving the superficial femoral artery and/or the popliteal artery. Cases were divided into a PRE and a POST era with a cutoff of September 2016, when specific device identity was first recorded in Vascular Quality Initiative. For each artery, a primary treatment was identified as either plain balloon angioplasty, atherectomy, DCB, bare-metal stent, or DES. The relative distribution of primary treatments between the PRE and POST eras was evaluated, as were lesion characteristics associated with DCB and DES use and regional variability in the adoption of these new technologies.Of 210,666 arteries in the dataset, 91,864 femoropopliteal arteries (across 74,842 procedures in 55,437 patients) were included. Each artery received 1.5 ± 0.6 treatments. Primary treatment use changed from 40% balloon angioplasty, 45% stenting, and 15% atherectomy in the PRE era to 22% plain balloon angioplasty, 26% bare-metal stent, 8% atherectomy, 37% DCB, and 8% DES in the POST era (P .001). Forty-three percent of arteries received a drug-containing device as a primary or adjunctive therapy and 1.3% received both a DCB and DES in the POST era. DCB use as the primary treatment was highest in lesions with length 10.0 to 19.9 cm (42%), TransAtlantic InterSociety A, B, or C lesions (38%), and lesions with mild to no calcification (38%). DES use was highest in lesions with a length of 20 cm or more (12%), TransAtlantic InterSociety D lesions (13%), and lesions with moderate to severe calcification (9%). The range of use across 18 regions was 125 to 40% for DCB and 1% to 14% for DES. Regional variability was greater for DES (SD 4% vs mean 8%) than for DCB (SD 7% vs mean 29%).There has been a rapid dissemination of DCB and DES technology in the femoropopliteal vessels, with nearly one-half of arteries receiving a drug-containing therapy in modern practice. DCBs are most used in medium length, minimally calcified lesions and DESs are most used in longer, more heavily calcified lesions. There is significant regional variability in adoption, especially with DES.

Published
2020
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43. Pseudochrobactrum algeriensis Loperena-Barber & Khames & Leclercq & Zygmunt & Babot & Z����iga-Ripa & Guti��rrez & Oumouna & Moriy��n & Cloeckaert & Conde-��lvarez 2022, SP. NOV

Author

Loperena-Barber, Maite, Khames, Mammar, Leclercq, S��bastien O., Zygmunt, Michel S., Babot, Esteban D., Z����iga-Ripa, Amaia, Guti��rrez, Ana, Oumouna, Mustapha, Moriy��n, Ignacio, Cloeckaert, Axel, and Conde-��lvarez, Raquel

Subjects
Pseudochrobactrum, Bacteria, Proteobacteria, Biodiversity, Rhizobiales, Taxonomy, Alphaproteobacteria, Brucellaceae, Pseudochrobactrum algeriensis
Abstract

DESCRIPTION OF PSEUDOCHROBACTRUM ALGERIENSIS SP. NOV. Pseudochrobactrum algeriensis (al.ge.ri.en��sis. N.L. masc. adj. algeriensis of or belonging to Algeria, referring to the isolation place). Aerobic, Gram-stain-negative, oxidase- and catalase-positive, non-motile and rod-shaped. Non-pigmented, beige colonies with regular edges with a diameter of about 2 mm. Good growth occurs at 18���38��C within 24���48h on TSA, nutrient agar, MacConkey and CPSE. In API 20NE tests, urease, cytochrome oxidase, citrate utilization and assimilation of D-glucose,D-mannose,L-malate, and N -acetylD -glucosamine are positive. Denitrification, indole production, D-glucose fermentation, arginine dihydrolase, aesculin hydrolysis (��-glucosidase), gelatin hydrolysis (protease), ��-galactosidase and assimilation of gluconate, capric acid, adipic acid, phenylacetic acid, L-arabinose, maltose and D-mannitol are negative. The major fatty acids are C 18:0 and C 18:1. The polar lipid profile consists of the major compounds phosphatidylethanolamine, ornithine-lipids, phosphatidylglycerol, cardiolipin and phosphatidylcholine, plus moderate amounts of PMME, PDME and other aminolipids. The type strain is C130915_07 T (CECT 30232 T =LMG 32378 T) isolated from lymph nodes of an Algerian cow., Published as part of Loperena-Barber, Maite, Khames, Mammar, Leclercq, S��bastien O., Zygmunt, Michel S., Babot, Esteban D., Z����iga-Ripa, Amaia, Guti��rrez, Ana, Oumouna, Mustapha, Moriy��n, Ignacio, Cloeckaert, Axel & Conde-��lvarez, Raquel, 2022, Pseudochrobactrum algeriensis sp. nov., isolated from lymph nodes of Algerian cattle, pp. 1-7 in International Journal of Systematic and Evolutionary Microbiology (005223) (005223) 72 (2) on page 6, DOI: 10.1099/ijsem.0.005223, http://zenodo.org/record/6224086

Published
2022
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44. Pseudochrobactrum algeriensis Loperena-Barber & Khames & Leclercq & Zygmunt & Babot & Zúñiga-Ripa & Gutiérrez & Oumouna & Moriyón & Cloeckaert & Conde-Álvarez 2022, SP. NOV

Author

Loperena-Barber, Maite, Khames, Mammar, Leclercq, Sébastien O., Zygmunt, Michel S., Babot, Esteban D., Zúñiga-Ripa, Amaia, Gutiérrez, Ana, Oumouna, Mustapha, Moriyón, Ignacio, Cloeckaert, Axel, and Conde-Álvarez, Raquel

Subjects
Pseudochrobactrum, Bacteria, Proteobacteria, Biodiversity, Rhizobiales, Taxonomy, Alphaproteobacteria, Brucellaceae, Pseudochrobactrum algeriensis
Abstract

DESCRIPTION OF PSEUDOCHROBACTRUM ALGERIENSIS SP. NOV. Pseudochrobactrum algeriensis (al.ge.ri.en´sis. N.L. masc. adj. algeriensis of or belonging to Algeria, referring to the isolation place). Aerobic, Gram-stain-negative, oxidase- and catalase-positive, non-motile and rod-shaped. Non-pigmented, beige colonies with regular edges with a diameter of about 2 mm. Good growth occurs at 18–38°C within 24–48h on TSA, nutrient agar, MacConkey and CPSE. In API 20NE tests, urease, cytochrome oxidase, citrate utilization and assimilation of D-glucose,D-mannose,L-malate, and N -acetylD -glucosamine are positive. Denitrification, indole production, D-glucose fermentation, arginine dihydrolase, aesculin hydrolysis (β-glucosidase), gelatin hydrolysis (protease), β-galactosidase and assimilation of gluconate, capric acid, adipic acid, phenylacetic acid, L-arabinose, maltose and D-mannitol are negative. The major fatty acids are C 18:0 and C 18:1. The polar lipid profile consists of the major compounds phosphatidylethanolamine, ornithine-lipids, phosphatidylglycerol, cardiolipin and phosphatidylcholine, plus moderate amounts of PMME, PDME and other aminolipids. The type strain is C130915_07 T (CECT 30232 T =LMG 32378 T) isolated from lymph nodes of an Algerian cow.

Published
2022
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45. Recurrence of COVID-19 associated with reduced T-cell responses in a monozygotic twin pair

Author

Mateus V. de Castro, Keity S. Santos, Juliana S. Apostolico, Edgar R. Fernandes, Rafael R. Almeida, Gabriel Levin, Jhosiene Y. Magawa, João Paulo S. Nunes, Mirian Bruni, Marcio M. Yamamoto, Ariane C. Lima, Monize V. R. Silva, Larissa R. B. Matos, Vivian R. Coria, Erick C. Castelli, Marilia O. Scliar, Andreia Kuramoto, Fernanda R. Bruno, Lucas C. Jacintho, Kelly Nunes, Jaqueline Y. T. Wang, Veronica P. Coelho, Miguel Mitne Neto, Rui M. B. Maciel, Michel S. Naslavsky, Maria Rita Passos-Bueno, Silvia B. Boscardin, Daniela S. Rosa, Jorge Kalil, Mayana Zatz, Edecio Cunha-Neto, Universidade de São Paulo (USP), Instituto Nacional de Ciência e Tecnologia - Iii-INCT, Universidade Federal de São Paulo (UNIFESP), Universidade Estadual Paulista (UNESP), and Fleury Laboratory

Subjects
Adult, Male, Immunity, Cellular, recurrence, Adolescent, SARS-CoV-2, QH301-705.5, T-Lymphocytes, Research, severe acute respiratory distress syndrome coronavirus 2, General Neuroscience, Immunology, Epitopes, T-Lymphocyte, COVID-19, T cell, Twins, Monozygotic, twins, immunity, General Biochemistry, Genetics and Molecular Biology, Humans, Female, Biology (General), IMUNOGENÉTICA, Research Articles
Abstract

Made available in DSpace on 2022-04-29T08:46:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Recurrence of COVID-19 in recovered patients has been increasingly reported. However, the immune mechanisms behind the recurrence have not been thoroughly investigated. The presence of neutralizing antibodies (nAbs) in recurrence/reinfection cases suggests that other types of immune response are involved in protection against recurrence. Here, we investigated the innate type I/III interferon (IFN) response, binding and nAb assays and T-cell responses to severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) with IFN gamma (IFNγ) enzyme-linked spot assay (ELISPOT) in three pairs of young adult monozygotic (MZ) twins with previous confirmed COVID-19, one of them presenting a severe recurrence four months after the initial infection. Twin studies have been of paramount importance to comprehend the immunogenetics of infectious diseases. Each MZ twin pair was previously exposed to SARS-CoV-2, as seen by clinical reports. The six individuals presented similar overall recovered immune responses except for the recurrence case, who presented a drastically reduced number of recognized SARS-CoV-2 T-cell epitopes on ELISPOT as compared to her twin sister and the other twin pairs. Our results suggest that the lack of a broad T-cell response to initial infection may have led to recurrence, emphasizing that an effective SARS-CoV-2-specific T-cell immune response is key for complete viral control and avoidance of clinical recurrence of COVID-19. Human Genome and Stem Cell Research Center (HUG-CELL) Biosciences Institute Universidade de São Paulo, SP Laboratory of Immunology Heart Institute (InCor) Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), SP Institute for Investigation in Immunology Instituto Nacional de Ciência e Tecnologia - Iii-INCT, SP Division of Clinical Immunology and Allergy Department of Medicine Faculdade de Medicina da Universidade de São Paulo (FMUSP), SP Department of Microbiology Immunology and Parasitology Universidade Federal de São Paulo (UNIFESP/EPM), SP Department of Parasitology Biosciences Institute Universidade de São Paulo, SP School of Medicine Universidade Estadual Paulista (UNESP), SP Fleury Laboratory, SP School of Medicine Universidade Estadual Paulista (UNESP), SP

Published
2022
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46. Associations between organised leisure-time activities and mental health problems in children

Author

Mirte, Boelens, Michel S, Smit, Dafna A, Windhorst, Harrie J, Jonkman, Clemens M H, Hosman, Hein, Raat, and Wilma, Jansen

Subjects
Cross-Sectional Studies, Leisure Activities, Mental Health, Adolescent, Humans, Child, Exercise, Sports
Abstract

Previous studies conducted mainly among adolescents have found associations between participation in sport organised leisure-time activities (OLTAs) and mental health problems (MHP). Fewer research studies have been performed to primary school-aged children and to organised non-sport OLTAs. Therefore, the objective is to examine whether there is an association between participation in sport and non-sport OLTAs and a high risk of MHP in 4- to 12-year-olds. Data were used on 5010 children from a cross-sectional population-based survey conducted between May and July 2018 in Rotterdam, the Netherlands. Associations between sport OLTAs, non-sport OLTAs and breadth of OLTAs and a high risk of MHP were explored using logistic regression models adjusting for sociodemographic characteristics, stressful life events and physical activity. Of all children, 58% participated in sport OLTAs and 22% in non-sport OLTAs. The proportion of children with high risk of MHP among participants in sport OLTAs is smaller than among non-participants (OR 0.66, 95% CI: 0.53, 0.81). The proportion of children with high risk of MHP among participants in non-sport OLTAs is smaller than among non-participants (OR 0.69, 95% CI: 0.53, 0.91). The proportion of children with a high risk of MHP among participants in 1 category of OLTAs (OR 0.61, 95% CI: 0.49, 0.76) and in 2-5 categories of OLTAs (OR 0.48, 95% CI: 0.32, 0.71) is smaller than among non-participants. Conclusion: The proportion of children with high risk of MHP among participants in OLTAs is smaller than among non-participants. What is Known: • Around 10--20% of children and adolescents experiences mental health problems. • Sport organised leisure-time activities have been found to be associated with a lower risk of mental health problems in adolescents. What is New: • The proportion of children with a high risk of mental health problems in participants in organised leisure-time activities is smaller than among non-participants. • The proportion of children with a high risk of mental health problems in participants with a higher breadth of organised leisure-time activities is smaller compared to non-participants.

Published
2022

49. Associations between organised leisure-time activities and mental health problems in children

Author

Mirte Boelens, Michel S. Smit, Dafna A. Windhorst, Harrie J. Jonkman, Clemens M. H. Hosman, Hein Raat, Wilma Jansen, and Public Health

Subjects
Experimental Psychopathology and Treatment, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Pediatrics, Perinatology and Child Health, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13]
Abstract

Previous studies conducted mainly among adolescents have found associations between participation in sport organised leisure-time activities (OLTAs) and mental health problems (MHP). Fewer research studies have been performed to primary school-aged children and to organised non-sport OLTAs. Therefore, the objective is to examine whether there is an association between participation in sport and non-sport OLTAs and a high risk of MHP in 4- to 12-year-olds. Data were used on 5010 children from a cross-sectional population-based survey conducted between May and July 2018 in Rotterdam, the Netherlands. Associations between sport OLTAs, non-sport OLTAs and breadth of OLTAs and a high risk of MHP were explored using logistic regression models adjusting for sociodemographic characteristics, stressful life events and physical activity. Of all children, 58% participated in sport OLTAs and 22% in non-sport OLTAs. The proportion of children with high risk of MHP among participants in sport OLTAs is smaller than among non-participants (OR 0.66, 95% CI: 0.53, 0.81). The proportion of children with high risk of MHP among participants in non-sport OLTAs is smaller than among non-participants (OR 0.69, 95% CI: 0.53, 0.91). The proportion of children with a high risk of MHP among participants in 1 category of OLTAs (OR 0.61, 95% CI: 0.49, 0.76) and in 2–5 categories of OLTAs (OR 0.48, 95% CI: 0.32, 0.71) is smaller than among non-participants. Conclusion: The proportion of children with high risk of MHP among participants in OLTAs is smaller than among non-participants. What is Known:• Around 10–-20% of children and adolescents experiences mental health problems.• Sport organised leisure-time activities have been found to be associated with a lower risk of mental health problems in adolescents. What is New:• The proportion of children with a high risk of mental health problems in participants in organised leisure-time activities is smaller than among non-participants.• The proportion of children with a high risk of mental health problems in participants with a higher breadth of organised leisure-time activities is smaller compared to non-participants.

Published
2022

50. Additional file 2 of The oldest unvaccinated Covid-19 survivors in South America

Author

de Castro, Mateus V., Silva, Monize V. R., Naslavsky, Michel S., Scliar, Marilia O., Nunes, Kelly, Passos-Bueno, Maria Rita, Castelli, Erick C., Magawa, Jhosiene Y., Adami, Flávia L., Moretti, Ana I. S., de Oliveira, Vivian L., Boscardin, Silvia B., Cunha-Neto, Edecio, Kalil, Jorge, Jouanguy, Emmanuelle, Bastard, Paul, Casanova, Jean-Laurent, Quiñones-Vega, Mauricio, Sosa-Acosta, Patricia, de Guedes, Jéssica S., de Almeida, Natália P., Nogueira, Fábio C. S., Domont, Gilberto B., Santos, Keity S., and Zatz, Mayana

Abstract

Supplementary Material 2

Published
2022
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